Colon and Rectal

TOPLINE:

A higher consumption of cruciferous vegetables such as broccoli and cauliflower was associated with a notably reduced risk for colon cancer (CC), with an optimal intake of 40-60 g/d providing a risk reduction of 20% to 26%.

METHODOLOGY:

• Previous meta-analyses have studied the association between the intake of cruciferous vegetables and the risk for CC; however, the quantitative dose-response relationship remained uncharacterized, limiting insights for dietary guidance.
• Researchers performed a systematic review and meta-analysis of 17 studies (seven cohort and 10 case-control studies) to analyze the dose-response association between the consumption of cruciferous vegetables and CC risk.
• Studies were included if they enrolled adults without CC at baseline (cohort studies) or adults with diagnosed cases who were matched with control individuals (case-control studies), quantified the dietary intake of cruciferous vegetables through standardized questionnaires, and included comparator groups with lower or no intake of such vegetables.
• The studies included 639,539 participants, of whom 97,595 had CC. Incident cases of CC were confirmed via medical records, pathology, registries, or validated self-report.

TAKEAWAY:

• A pooled analysis revealed that people who consumed the largest amounts of cruciferous vegetables had a 20% lower risk for CC than those who consumed the lowest amounts.
• A dose-response analysis showed that risk reduction was near maximal at an intake of 40-60 g/d (odds ratio, 0.74-0.8), with benefits plateauing beyond this range.
• The peak protective effect per gram occurred at an intake of 20-40 g/d of cruciferous vegetables and fell after 60 g/d.

IN PRACTICE:

“The pathophysiology of CC has been linked to dietary factors, specifically inadequate intake of vegetables and dietary fiber, as well as excessive alcohol and caffeine use. These empirical findings lend credence to our results, suggesting a potential chemopreventive role of CV [cruciferous vegetables] against CC development,” the authors wrote.

SOURCE:

This study, led by Bo Lai, Department of Interventional Radiology, The Second Clinical Medical School of Inner Mongolia University for the Nationalities, Yakeshi, China, was published online in BMC Gastroenterology.

LIMITATIONS:

The inclusion of both case-control and cohort studies and variations in the assessment of cruciferous vegetable intake across studies may have introduced methodological heterogeneity and measurement error, respectively. This study did not measure factors such as pesticide exposure and genetic susceptibility. The predominance of studies from North America and Asia — regions with an elevated incidence of CC — may have limited generalizability to other populations.

DISCLOSURES:

This study received no financial support. The authors declared having no competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. 

A version of this article first appeared on Medscape.com.

TOPLINE:

A higher consumption of cruciferous vegetables such as broccoli and cauliflower was associated with a notably reduced risk for colon cancer (CC), with an optimal intake of 40-60 g/d providing a risk reduction of 20% to 26%.

METHODOLOGY:

• Previous meta-analyses have studied the association between the intake of cruciferous vegetables and the risk for CC; however, the quantitative dose-response relationship remained uncharacterized, limiting insights for dietary guidance.
• Researchers performed a systematic review and meta-analysis of 17 studies (seven cohort and 10 case-control studies) to analyze the dose-response association between the consumption of cruciferous vegetables and CC risk.
• Studies were included if they enrolled adults without CC at baseline (cohort studies) or adults with diagnosed cases who were matched with control individuals (case-control studies), quantified the dietary intake of cruciferous vegetables through standardized questionnaires, and included comparator groups with lower or no intake of such vegetables.
• The studies included 639,539 participants, of whom 97,595 had CC. Incident cases of CC were confirmed via medical records, pathology, registries, or validated self-report.

TAKEAWAY:

• A pooled analysis revealed that people who consumed the largest amounts of cruciferous vegetables had a 20% lower risk for CC than those who consumed the lowest amounts.
• A dose-response analysis showed that risk reduction was near maximal at an intake of 40-60 g/d (odds ratio, 0.74-0.8), with benefits plateauing beyond this range.
• The peak protective effect per gram occurred at an intake of 20-40 g/d of cruciferous vegetables and fell after 60 g/d.

IN PRACTICE:

“The pathophysiology of CC has been linked to dietary factors, specifically inadequate intake of vegetables and dietary fiber, as well as excessive alcohol and caffeine use. These empirical findings lend credence to our results, suggesting a potential chemopreventive role of CV [cruciferous vegetables] against CC development,” the authors wrote.

SOURCE:

This study, led by Bo Lai, Department of Interventional Radiology, The Second Clinical Medical School of Inner Mongolia University for the Nationalities, Yakeshi, China, was published online in BMC Gastroenterology.

LIMITATIONS:

The inclusion of both case-control and cohort studies and variations in the assessment of cruciferous vegetable intake across studies may have introduced methodological heterogeneity and measurement error, respectively. This study did not measure factors such as pesticide exposure and genetic susceptibility. The predominance of studies from North America and Asia — regions with an elevated incidence of CC — may have limited generalizability to other populations.

DISCLOSURES:

This study received no financial support. The authors declared having no competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. 

A version of this article first appeared on Medscape.com.

TOPLINE:

A higher consumption of cruciferous vegetables such as broccoli and cauliflower was associated with a notably reduced risk for colon cancer (CC), with an optimal intake of 40-60 g/d providing a risk reduction of 20% to 26%.

METHODOLOGY:

• Previous meta-analyses have studied the association between the intake of cruciferous vegetables and the risk for CC; however, the quantitative dose-response relationship remained uncharacterized, limiting insights for dietary guidance.
• Researchers performed a systematic review and meta-analysis of 17 studies (seven cohort and 10 case-control studies) to analyze the dose-response association between the consumption of cruciferous vegetables and CC risk.
• Studies were included if they enrolled adults without CC at baseline (cohort studies) or adults with diagnosed cases who were matched with control individuals (case-control studies), quantified the dietary intake of cruciferous vegetables through standardized questionnaires, and included comparator groups with lower or no intake of such vegetables.
• The studies included 639,539 participants, of whom 97,595 had CC. Incident cases of CC were confirmed via medical records, pathology, registries, or validated self-report.

TAKEAWAY:

• A pooled analysis revealed that people who consumed the largest amounts of cruciferous vegetables had a 20% lower risk for CC than those who consumed the lowest amounts.
• A dose-response analysis showed that risk reduction was near maximal at an intake of 40-60 g/d (odds ratio, 0.74-0.8), with benefits plateauing beyond this range.
• The peak protective effect per gram occurred at an intake of 20-40 g/d of cruciferous vegetables and fell after 60 g/d.

IN PRACTICE:

“The pathophysiology of CC has been linked to dietary factors, specifically inadequate intake of vegetables and dietary fiber, as well as excessive alcohol and caffeine use. These empirical findings lend credence to our results, suggesting a potential chemopreventive role of CV [cruciferous vegetables] against CC development,” the authors wrote.

SOURCE:

This study, led by Bo Lai, Department of Interventional Radiology, The Second Clinical Medical School of Inner Mongolia University for the Nationalities, Yakeshi, China, was published online in BMC Gastroenterology.

LIMITATIONS:

The inclusion of both case-control and cohort studies and variations in the assessment of cruciferous vegetable intake across studies may have introduced methodological heterogeneity and measurement error, respectively. This study did not measure factors such as pesticide exposure and genetic susceptibility. The predominance of studies from North America and Asia — regions with an elevated incidence of CC — may have limited generalizability to other populations.

DISCLOSURES:

This study received no financial support. The authors declared having no competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. 

A version of this article first appeared on Medscape.com.

Screening for colorectal cancer (CRC) with colonoscopy enables the identification and removal of CRC precursors (colonic adenomas) and has been associated with reduced risk of CRC incidence and mortality.^1-3 Furthermore, there is consensus that diet and lifestyle may be associated with forestalling CRC pathogenesis at the intermediate adenoma stages.^4-7 However, studies have shown that US veterans have poorer diet quality and a higher risk for neoplasia compared with nonveterans, reinforcing the need for tailored clinical approaches.^8,9 Combining screening with conversations about modifiable environmental and lifestyle risk factors, such as poor diet, is a highly relevant and possibly easily leveraged prevention for those at high risk. However, there is limited evidence for any particular dietary patterns or dietary features that are most important over time.⁷

Several dietary components have been shown to be associated with CRC risk,10 either as potentially chemopreventive (fiber, fruits and vegetables,¹¹ dairy,¹² supplemental vitamin D,¹³ calcium,¹⁴ and multivitamins¹⁵) or carcinogenic (red meat¹⁶ and alcohol¹⁷). Previous studies of veterans have similarly shown that higher intake of fiber and vitamin D reduced risk, and red meat is associated with an increased risk for finding CRC precursors during colonoscopy.¹⁸ However, these dietary categories are often analyzed in isolation. Studying healthy dietary patterns in aggregate may be more clinically relevant and easier to implement for prevention of CRC and its precursors.^19-21 Healthy dietary patterns, such as the US Dietary Guidelines for Americans represented by the Healthy Eating Index (HEI), the Mediterranean diet (MD), and the Dietary Approaches to Stop Hypertension (DASH) diet, have been associated with lower risk for chronic disease.^22-24 Despite the extant literature, no known studies have compared these dietary patterns for associations with risk of CRC precursor or CRC development among US veterans undergoing long-term screening and follow-up after a baseline colonoscopy.

The objective of this study was to test for associations between baseline scores of healthy dietary patterns and the most severe colonoscopy findings (MSCFs) over ≥ 10 years following a baseline screening colonoscopy in veterans.

Methods

Participants in the Cooperative Studies Program (CSP) #380 cohort study included 3121 asymptomatic veterans aged 50 to 75 years at baseline who had consented to initial screening colonoscopy between 1994 and 1997, with subsequent follow-up and surveillance.²⁵ Prior to their colonoscopy, all participants completed a baseline study survey that included questions about cancer risk factors including family history of CRC, diet, physical activity, and medication use.

Included in this cross-sectional analysis were data from a sample of veteran participants of the CSP #380 cohort with 1 baseline colonoscopy, follow-up surveillance through 2009, a cancer risk factor survey collected at baseline, and complete demographic and clinical indicator data. Excluded from the analysis were 67 participants with insufficient responses to the dietary food frequency questionnaire (FFQ) and 31 participants with missing body mass index (BMI), 3023 veterans.

Measures

MSCF. The outcome of interest in this study was the MSCF recorded across all participant colonoscopies during the study period. MSCF was categorized as either (1) no neoplasia; (2) < 2 nonadvanced adenomas, including small adenomas (diameter < 10 mm) with tubular histology; or (3) advanced neoplasia (AN), which is characterized by adenomas > 10 mm in diameter, with villous histology, with high-grade dysplasia, or CRC.

Dietary patterns. Dietary pattern scores representing dietary quality and calculated based on recommendations of the US Dietary Guidelines for Americans using the HEI, MD, and DASH diets were independent variables.^26-28 These 3 dietary patterns were chosen for their hypothesized relationship with CRC risk, but each weighs food categories differently (Appendix 1).^22-24,29 Dietary pattern scores were calculated using the CSP #380 self-reported responses to 129 baseline survey questions adapted from a well-established and previously validated semiquantitative FFQ.³⁰ The form was administered by mail twice to a sample of 127 participants at baseline and at 1 year. During this interval, men completed 1-week diet records twice, spaced about 6 months apart. Mean values for intake of most nutrients assessed by the 2 methods were similar. Intraclass correlation coefficients for the baseline and 1-year FFQ-assessed nutrient intakes that ranged from 0.47 for vitamin E (without supplements) to 0.80 for vitamin C (with supplements). Correlation coefficients between the energy-adjusted nutrient intakes were measured by diet records and the 1-year FFQ, which asked about diet during the year encompassing the diet records. Higher raw and percent scores indicated better alignment with recommendations from each respective dietary pattern. Percent scores were calculated as a standardizing method and used in analyses for ease of comparing the dietary patterns. Scoring can be found in Appendix 2.

Demographic characteristics and clinical indicators. Demographic characteristics included age categories, sex, and race/ethnicity. Clinical indicators included BMI, the number of comorbid conditions used to calculate the Charlson Comorbidity Index, family history of CRC in first-degree relatives, number of follow-up colonoscopies across the study period, and food-based vitamin D intake.³¹ These variables were chosen for their applicability found in previous CSP #380 cohort studies.^18,32,33 Self-reported race and ethnicity were collapsed due to small numbers in some groups. The authors acknowledge these are distinct concepts and the variable has limited utility other than for controlling for systemic racism in the model.

Statistical Analyses

Descriptive statistics were used to describe distributional assumptions for all variables, including demographics, clinical indicators, colonoscopy results, and dietary patterns. Pairwise correlations between the total dietary pattern scores and food category scores were calculated with Pearson correlation (r).

Multinomial logistic regression models were created using SAS procedure LOGISTIC with the outcome of the categorical MSCF (no neoplasia, nonadvanced adenoma, or AN).³⁴ A model was created for each independent predictor variable of interest (ie, the HEI, MD, or DASH percentage-standardized dietary pattern score and each food category comprising each dietary pattern score). All models were adjusted for age, sex, race/ethnicity, BMI, number of comorbidities, family history of CRC, number of follow-up colonoscopies, and estimated daily food-derived vitamin D intake. The demographic and clinical indicators were included in the models as they are known to be associated with CRC risk.¹⁸ The number of colonoscopies was included to control for surveillance intensity presuming risk for AN is reduced as polyps are removed. Because colonoscopy findings from an initial screening have unique clinical implications compared with follow- up and surveillance, MSCF was observed in 2 ways in sensitivity analyses: (1) baseline and (2) aggregate follow-up and surveillance only, excluding baseline findings.

Adjusted odds ratios (aORs) and 95% CIs for each of the MSCF outcomes with a reference finding of no neoplasia for the models are presented. We chose not to adjust for multiple comparisons across the different dietary patterns given the correlation between dietary pattern total and category scores but did adjust for multiple comparisons for dietary categories within each dietary pattern. Tests for statistical significance used α= .05 for the dietary pattern total scores and P values for the dietary category scores for each dietary pattern controlled for false discovery rate using the MULTTEST SAS procedure.35 All data manipulations and analyses were performed using SAS version 9.4.

Results

The study included 3023 patients. All were aged 50 to 75 years, 2923 (96.7%) were male and 2532 (83.8%) were non-Hispanic White (Table 1). Most participants were overweight or obese (n = 2535 [83.8%]), 2024 (67.0%) had ≤ 2 comorbidities, and 2602 (86.1%) had no family history of CRC. The MSCF for 1628 patients (53.9%) was no neoplasia, 966 patients (32.0%) was nonadvanced adenoma, and 429 participants (14.2%) had AN.

Mean percent scores were 58.5% for HEI, 38.2% for MD, and 63.1% for the DASH diet, with higher percentages indicating greater alignment with the recommendations for each diet (Table 2). All 3 dietary patterns scores standardized to percentages were strongly and significantly correlated in pairwise comparisons: HEI:MD, r = 0.62 (P < .001); HEI:DASH, r = 0.60 (P < .001); and MD:DASH, r = 0.72 (P < .001). Likewise, food category scores were significantly correlated across dietary patterns. For example, whole grain and fiber values from each dietary score were strongly correlated in pairwise comparisons: HEI Whole Grain:MD Grain, r = 0.64 (P < .001); HEI Whole Grain:DASH Fiber, r = 0.71 (P < .001); and MD Grain:DASH Fiber, r = 0.70 (P < .001).

Associations between individual participants' dietary pattern scores and the outcome of their pooled MSCF from baseline screening and ≥ 10 years of surveillance are presented in Table 3. For each single-point increases in dietary pattern scores (reflecting better dietary quality), aORs for nonadvanced adenoma vs no neoplasia were slightly lower but not statistically significantly: HEI, aOR, 1.00 (95% CI, 0.99-1.01); MD, aOR, 0.98 (95% CI, 0.94-1.02); and DASH, aOR, 0.99 (95% CI, 0.99-1.00). aORs for AN vs no neoplasia were slightly lower for each dietary pattern assessed, and only the MD and DASH scores were significantly different from 1.00: HEI, aOR, 1.00 (95% CI, 0.99-1.01); MD, aOR, 0.95 (95% CI, 0.90-1.00); and DASH, aOR, 0.99 (95% CI, 0.98-1.00).

We observed lower odds for nonadvanced adenoma and AN among all these dietary patterns when there was greater alignment with the recommended intake of whole grains and fiber. In separate models conducted using food categories comprising the dietary patterns as independent variables and after correcting for multiple tests, higher scores for the HEI Refined Grain category were associated with higher odds for nonadvanced adenoma (aOR, 1.03 [95% CI, 1.01-1.05]; P = .01) and AN (aOR, 1.05 [95% CI, 1.02-1.08]; P < .001). Higher scores for the HEI Whole Grain category were associated with lower odds for nonadvanced adenoma (aOR, 0.97 [95% CI, 0.95-0.99]; P = .01) and AN (aOR, 0.96 [95% CI, 0.93-0.99]; P = .01). Higher scores for the MD Grain category were significantly associated with lower odds for nonadvanced adenoma (aOR, 0.44 [95% CI, 0.26-0.75]; P = .002) and AN (aOR, 0.29 [95% CI, 0.14-0.62]; P = .001). The DASH Grains category also was significantly associated with lower odds for AN (aOR, 0.86 [95% CI, 0.78-0.95]; P = .002).

Discussion

In this study of 3023 veterans undergoing first-time screening colonoscopy and ≥ 10 years of surveillance, we found that healthy dietary patterns, as assessed by the MD and DASH diet, were significantly associated with lower risk of AN. Additionally, we identified lower odds for AN and nonadvanced adenoma compared with no neoplasia for higher grain scores for all the dietary patterns studied. Other food categories that comprise the dietary pattern scores had mixed associations with the MSCF outcomes. Several other studies have examined associations between dietary patterns and risk for CRC but to our knowledge, no studies have explored these associations among US veterans.

These results also indicate study participants had better than average (based on a 50% threshold) dietary quality according to the HEI and DASH diet scoring methods we used, but poor dietary quality according to the MD scoring method. The mean HEI scores for the present study were higher than a US Department of Agriculture study by Dong et al that compared dietary quality between veterans and nonveterans using the HEI, for which veterans’ expected HEI score was 45.6 of 100.⁸ This could be explained by the fact that the participants needed to be healthy to be eligible and those with healthier behaviors overall may have self-selected into the study due to motivation for screening during a time when screening was not yet commonplace. ³⁶ Similarly, participants of the present study had higher adherence to the DASH diet (63.1%) than adolescents with diabetes in a study by Günther et al. Conversely, firefighters who were coached to use a Mediterranean-style dietary pattern and dietary had higher adherence to MD than did participants in this study.²⁷

A closer examination of specific food category component scores that comprise the 3 distinct dietary patterns revealed mixed results from the multinomial modeling, which may have to do with the guideline thresholds used to calculate the dietary scores. When analyzed separately in the logistic regression models for their associations with nonadvanced adenomas and AN compared with no neoplasia, higher MD and DASH fruit scores (but not HEI fruit scores) were found to be significant. Other studies have had mixed findings when attempting to test for associations of fruit intake with adenoma recurrence.^10,37

This study had some unexpected findings. Vegetable intake was not associated with nonadvanced adenomas or AN risk. Studies of food categories have consistently found vegetable (specifically cruciferous ones) intake to be linked with lower odds for cancers.³⁸ Likewise, the red meat category, which was only a unique food category in the MD score, was not associated with nonadvanced adenomas or AN. Despite consistent literature suggesting higher intake of red meat and processed meats increases CRC risk, in 2019 the Nutritional Recommendations Consortium indicated that the evidence was weak.^39,40 This study showed higher DASH diet scores for low-fat dairy, which were maximized when participants reported at least 50% of their dairy servings per day as being low-fat, had lower odds for AN. Yet, the MD scores for low-fat dairy had no association with either outcome; their calculation was based on total number of servings per week. This difference in findings suggests the fat intake ratio may be more relevant to CRC risk than intake quantity.

The literature is mixed regarding fatty acid intake and CRC risk, which may be relevant to both dairy and meat intake. One systematic review and meta-analysis found dietary fat and types of fatty acid intake had no association with CRC risk.⁴¹ However, a more recent meta-analysis that assessed both dietary intake and plasma levels of fatty acids did find some statistically significant differences for various types of fatty acids and CRC risk.⁴²

The findings in the present study that grain intake is associated with lower odds for more severe colonoscopy findings among veterans are notable.⁴³ Lieberman et al, using the CSP #380 data, found that cereal fiber intake was associated with a lower odds for AN compared with hyperplastic polyps (OR, 0.98 [95% CI, 0.96- 1.00]).¹⁸ Similarly, Hullings et al determined that older adults in the highest quintile of cereal fiber intake had significantly lower odds of CRC than those in lower odds for CRC when compared with lowest quintile (OR, 0.89 [95% CI, 0.83- 0.96]; P < .001).⁴⁴ These findings support existing guidance that prioritizes whole grains as a key source of dietary fiber for CRC prevention.

A recent literature review on fiber, fat, and CRC risk suggested a consensus regarding one protective mechanism: dietary fiber from grains modulates the gut microbiota by promoting butyrate synthesis.⁴⁵ Butyrate is a short-chain fatty acid that supports energy production in colonocytes and has tumor-suppressing properties.⁴⁶ Our findings suggest there could be more to learn about the relationship between butyrate production and reduction of CRC risk through metabolomic studies that use measurements of plasma butyrate. These studies may examine associations between not just a singular food or food category, but rather food patterns that include fruits, vegetables, nuts and seeds, and whole grains known to promote butyrate production and plasma butyrate.⁴⁷

Improved understanding of mechanisms and risk-modifying lifestyle factors such as dietary patterns may enhance prevention strategies. Identifying the collective chemopreventive characteristics of a specific dietary pattern (eg, MD) will be helpful to clinicians and health care staff to promote healthy eating to reduce cancer risk. More studies are needed to understand whether such promotion is more clinically applicable and effective for patients, as compared with eating more or less of specific foods (eg, more whole grains, less red meat). Furthermore, considering important environmental factors collectively beyond dietary patterns may offer a way to better tailor screening and implement a variety of lifestyle interventions. In the literature, this is often referred to as a teachable moment when patients’ attentions are captured and may position them to be more receptive to guidance.⁴⁸

Limitations

This study has several important limitations and leaves opportunities for future studies that explore the role of dietary patterns and AN or CRC risk. First, the FFQ data used to calculate dietary pattern scores used in analysis were only captured at baseline, and there are nearly 3 decades across the study period. However, it is widely assumed that the diets of older adults, like those included in this study, remain stable over time which is appropriate given our sample population was aged 50 to 75 years when the baseline FFQ data were collected.^49-51 Additionally, while the HEI is a well-documented, standard scoring method for dietary quality, there are multitudes of dietary pattern scoring approaches for MD and DASH.^23,52,53 Finally, findings from this study using the sample of veterans may not be generalizable to a broader population. Future longitudinal studies that test for a clinically significant change threshold are warranted.

Conclusion

Results of this study suggest future research should further explore the effects of dietary patterns, particularly intake of specific food groups in combination, as opposed to individual nutrients or food items, on AN and CRC risk. Possible studies might explore these dietary patterns for their mechanistic role in altering the microbiome metabolism, which may influence CRC outcomes or include diet in a more comprehensive, holistic risk score that could be used to predict colonic neoplasia risk or in intervention studies that assess the effects of dietary changes on long-term CRC prevention. We suggest there are differences in people’s dietary intake patterns that might be important to consider when implementing tailored approaches to CRC risk mitigation.

Screening for colorectal cancer (CRC) with colonoscopy enables the identification and removal of CRC precursors (colonic adenomas) and has been associated with reduced risk of CRC incidence and mortality.^1-3 Furthermore, there is consensus that diet and lifestyle may be associated with forestalling CRC pathogenesis at the intermediate adenoma stages.^4-7 However, studies have shown that US veterans have poorer diet quality and a higher risk for neoplasia compared with nonveterans, reinforcing the need for tailored clinical approaches.^8,9 Combining screening with conversations about modifiable environmental and lifestyle risk factors, such as poor diet, is a highly relevant and possibly easily leveraged prevention for those at high risk. However, there is limited evidence for any particular dietary patterns or dietary features that are most important over time.⁷

Several dietary components have been shown to be associated with CRC risk,10 either as potentially chemopreventive (fiber, fruits and vegetables,¹¹ dairy,¹² supplemental vitamin D,¹³ calcium,¹⁴ and multivitamins¹⁵) or carcinogenic (red meat¹⁶ and alcohol¹⁷). Previous studies of veterans have similarly shown that higher intake of fiber and vitamin D reduced risk, and red meat is associated with an increased risk for finding CRC precursors during colonoscopy.¹⁸ However, these dietary categories are often analyzed in isolation. Studying healthy dietary patterns in aggregate may be more clinically relevant and easier to implement for prevention of CRC and its precursors.^19-21 Healthy dietary patterns, such as the US Dietary Guidelines for Americans represented by the Healthy Eating Index (HEI), the Mediterranean diet (MD), and the Dietary Approaches to Stop Hypertension (DASH) diet, have been associated with lower risk for chronic disease.^22-24 Despite the extant literature, no known studies have compared these dietary patterns for associations with risk of CRC precursor or CRC development among US veterans undergoing long-term screening and follow-up after a baseline colonoscopy.

The objective of this study was to test for associations between baseline scores of healthy dietary patterns and the most severe colonoscopy findings (MSCFs) over ≥ 10 years following a baseline screening colonoscopy in veterans.

Methods

Participants in the Cooperative Studies Program (CSP) #380 cohort study included 3121 asymptomatic veterans aged 50 to 75 years at baseline who had consented to initial screening colonoscopy between 1994 and 1997, with subsequent follow-up and surveillance.²⁵ Prior to their colonoscopy, all participants completed a baseline study survey that included questions about cancer risk factors including family history of CRC, diet, physical activity, and medication use.

Included in this cross-sectional analysis were data from a sample of veteran participants of the CSP #380 cohort with 1 baseline colonoscopy, follow-up surveillance through 2009, a cancer risk factor survey collected at baseline, and complete demographic and clinical indicator data. Excluded from the analysis were 67 participants with insufficient responses to the dietary food frequency questionnaire (FFQ) and 31 participants with missing body mass index (BMI), 3023 veterans.

Measures

MSCF. The outcome of interest in this study was the MSCF recorded across all participant colonoscopies during the study period. MSCF was categorized as either (1) no neoplasia; (2) < 2 nonadvanced adenomas, including small adenomas (diameter < 10 mm) with tubular histology; or (3) advanced neoplasia (AN), which is characterized by adenomas > 10 mm in diameter, with villous histology, with high-grade dysplasia, or CRC.

Dietary patterns. Dietary pattern scores representing dietary quality and calculated based on recommendations of the US Dietary Guidelines for Americans using the HEI, MD, and DASH diets were independent variables.^26-28 These 3 dietary patterns were chosen for their hypothesized relationship with CRC risk, but each weighs food categories differently (Appendix 1).^22-24,29 Dietary pattern scores were calculated using the CSP #380 self-reported responses to 129 baseline survey questions adapted from a well-established and previously validated semiquantitative FFQ.³⁰ The form was administered by mail twice to a sample of 127 participants at baseline and at 1 year. During this interval, men completed 1-week diet records twice, spaced about 6 months apart. Mean values for intake of most nutrients assessed by the 2 methods were similar. Intraclass correlation coefficients for the baseline and 1-year FFQ-assessed nutrient intakes that ranged from 0.47 for vitamin E (without supplements) to 0.80 for vitamin C (with supplements). Correlation coefficients between the energy-adjusted nutrient intakes were measured by diet records and the 1-year FFQ, which asked about diet during the year encompassing the diet records. Higher raw and percent scores indicated better alignment with recommendations from each respective dietary pattern. Percent scores were calculated as a standardizing method and used in analyses for ease of comparing the dietary patterns. Scoring can be found in Appendix 2.

Demographic characteristics and clinical indicators. Demographic characteristics included age categories, sex, and race/ethnicity. Clinical indicators included BMI, the number of comorbid conditions used to calculate the Charlson Comorbidity Index, family history of CRC in first-degree relatives, number of follow-up colonoscopies across the study period, and food-based vitamin D intake.³¹ These variables were chosen for their applicability found in previous CSP #380 cohort studies.^18,32,33 Self-reported race and ethnicity were collapsed due to small numbers in some groups. The authors acknowledge these are distinct concepts and the variable has limited utility other than for controlling for systemic racism in the model.

Statistical Analyses

Descriptive statistics were used to describe distributional assumptions for all variables, including demographics, clinical indicators, colonoscopy results, and dietary patterns. Pairwise correlations between the total dietary pattern scores and food category scores were calculated with Pearson correlation (r).

Multinomial logistic regression models were created using SAS procedure LOGISTIC with the outcome of the categorical MSCF (no neoplasia, nonadvanced adenoma, or AN).³⁴ A model was created for each independent predictor variable of interest (ie, the HEI, MD, or DASH percentage-standardized dietary pattern score and each food category comprising each dietary pattern score). All models were adjusted for age, sex, race/ethnicity, BMI, number of comorbidities, family history of CRC, number of follow-up colonoscopies, and estimated daily food-derived vitamin D intake. The demographic and clinical indicators were included in the models as they are known to be associated with CRC risk.¹⁸ The number of colonoscopies was included to control for surveillance intensity presuming risk for AN is reduced as polyps are removed. Because colonoscopy findings from an initial screening have unique clinical implications compared with follow- up and surveillance, MSCF was observed in 2 ways in sensitivity analyses: (1) baseline and (2) aggregate follow-up and surveillance only, excluding baseline findings.

Adjusted odds ratios (aORs) and 95% CIs for each of the MSCF outcomes with a reference finding of no neoplasia for the models are presented. We chose not to adjust for multiple comparisons across the different dietary patterns given the correlation between dietary pattern total and category scores but did adjust for multiple comparisons for dietary categories within each dietary pattern. Tests for statistical significance used α= .05 for the dietary pattern total scores and P values for the dietary category scores for each dietary pattern controlled for false discovery rate using the MULTTEST SAS procedure.35 All data manipulations and analyses were performed using SAS version 9.4.

Results

The study included 3023 patients. All were aged 50 to 75 years, 2923 (96.7%) were male and 2532 (83.8%) were non-Hispanic White (Table 1). Most participants were overweight or obese (n = 2535 [83.8%]), 2024 (67.0%) had ≤ 2 comorbidities, and 2602 (86.1%) had no family history of CRC. The MSCF for 1628 patients (53.9%) was no neoplasia, 966 patients (32.0%) was nonadvanced adenoma, and 429 participants (14.2%) had AN.

Mean percent scores were 58.5% for HEI, 38.2% for MD, and 63.1% for the DASH diet, with higher percentages indicating greater alignment with the recommendations for each diet (Table 2). All 3 dietary patterns scores standardized to percentages were strongly and significantly correlated in pairwise comparisons: HEI:MD, r = 0.62 (P < .001); HEI:DASH, r = 0.60 (P < .001); and MD:DASH, r = 0.72 (P < .001). Likewise, food category scores were significantly correlated across dietary patterns. For example, whole grain and fiber values from each dietary score were strongly correlated in pairwise comparisons: HEI Whole Grain:MD Grain, r = 0.64 (P < .001); HEI Whole Grain:DASH Fiber, r = 0.71 (P < .001); and MD Grain:DASH Fiber, r = 0.70 (P < .001).

Associations between individual participants' dietary pattern scores and the outcome of their pooled MSCF from baseline screening and ≥ 10 years of surveillance are presented in Table 3. For each single-point increases in dietary pattern scores (reflecting better dietary quality), aORs for nonadvanced adenoma vs no neoplasia were slightly lower but not statistically significantly: HEI, aOR, 1.00 (95% CI, 0.99-1.01); MD, aOR, 0.98 (95% CI, 0.94-1.02); and DASH, aOR, 0.99 (95% CI, 0.99-1.00). aORs for AN vs no neoplasia were slightly lower for each dietary pattern assessed, and only the MD and DASH scores were significantly different from 1.00: HEI, aOR, 1.00 (95% CI, 0.99-1.01); MD, aOR, 0.95 (95% CI, 0.90-1.00); and DASH, aOR, 0.99 (95% CI, 0.98-1.00).

We observed lower odds for nonadvanced adenoma and AN among all these dietary patterns when there was greater alignment with the recommended intake of whole grains and fiber. In separate models conducted using food categories comprising the dietary patterns as independent variables and after correcting for multiple tests, higher scores for the HEI Refined Grain category were associated with higher odds for nonadvanced adenoma (aOR, 1.03 [95% CI, 1.01-1.05]; P = .01) and AN (aOR, 1.05 [95% CI, 1.02-1.08]; P < .001). Higher scores for the HEI Whole Grain category were associated with lower odds for nonadvanced adenoma (aOR, 0.97 [95% CI, 0.95-0.99]; P = .01) and AN (aOR, 0.96 [95% CI, 0.93-0.99]; P = .01). Higher scores for the MD Grain category were significantly associated with lower odds for nonadvanced adenoma (aOR, 0.44 [95% CI, 0.26-0.75]; P = .002) and AN (aOR, 0.29 [95% CI, 0.14-0.62]; P = .001). The DASH Grains category also was significantly associated with lower odds for AN (aOR, 0.86 [95% CI, 0.78-0.95]; P = .002).

Discussion

In this study of 3023 veterans undergoing first-time screening colonoscopy and ≥ 10 years of surveillance, we found that healthy dietary patterns, as assessed by the MD and DASH diet, were significantly associated with lower risk of AN. Additionally, we identified lower odds for AN and nonadvanced adenoma compared with no neoplasia for higher grain scores for all the dietary patterns studied. Other food categories that comprise the dietary pattern scores had mixed associations with the MSCF outcomes. Several other studies have examined associations between dietary patterns and risk for CRC but to our knowledge, no studies have explored these associations among US veterans.

These results also indicate study participants had better than average (based on a 50% threshold) dietary quality according to the HEI and DASH diet scoring methods we used, but poor dietary quality according to the MD scoring method. The mean HEI scores for the present study were higher than a US Department of Agriculture study by Dong et al that compared dietary quality between veterans and nonveterans using the HEI, for which veterans’ expected HEI score was 45.6 of 100.⁸ This could be explained by the fact that the participants needed to be healthy to be eligible and those with healthier behaviors overall may have self-selected into the study due to motivation for screening during a time when screening was not yet commonplace. ³⁶ Similarly, participants of the present study had higher adherence to the DASH diet (63.1%) than adolescents with diabetes in a study by Günther et al. Conversely, firefighters who were coached to use a Mediterranean-style dietary pattern and dietary had higher adherence to MD than did participants in this study.²⁷

A closer examination of specific food category component scores that comprise the 3 distinct dietary patterns revealed mixed results from the multinomial modeling, which may have to do with the guideline thresholds used to calculate the dietary scores. When analyzed separately in the logistic regression models for their associations with nonadvanced adenomas and AN compared with no neoplasia, higher MD and DASH fruit scores (but not HEI fruit scores) were found to be significant. Other studies have had mixed findings when attempting to test for associations of fruit intake with adenoma recurrence.^10,37

This study had some unexpected findings. Vegetable intake was not associated with nonadvanced adenomas or AN risk. Studies of food categories have consistently found vegetable (specifically cruciferous ones) intake to be linked with lower odds for cancers.³⁸ Likewise, the red meat category, which was only a unique food category in the MD score, was not associated with nonadvanced adenomas or AN. Despite consistent literature suggesting higher intake of red meat and processed meats increases CRC risk, in 2019 the Nutritional Recommendations Consortium indicated that the evidence was weak.^39,40 This study showed higher DASH diet scores for low-fat dairy, which were maximized when participants reported at least 50% of their dairy servings per day as being low-fat, had lower odds for AN. Yet, the MD scores for low-fat dairy had no association with either outcome; their calculation was based on total number of servings per week. This difference in findings suggests the fat intake ratio may be more relevant to CRC risk than intake quantity.

The literature is mixed regarding fatty acid intake and CRC risk, which may be relevant to both dairy and meat intake. One systematic review and meta-analysis found dietary fat and types of fatty acid intake had no association with CRC risk.⁴¹ However, a more recent meta-analysis that assessed both dietary intake and plasma levels of fatty acids did find some statistically significant differences for various types of fatty acids and CRC risk.⁴²

The findings in the present study that grain intake is associated with lower odds for more severe colonoscopy findings among veterans are notable.⁴³ Lieberman et al, using the CSP #380 data, found that cereal fiber intake was associated with a lower odds for AN compared with hyperplastic polyps (OR, 0.98 [95% CI, 0.96- 1.00]).¹⁸ Similarly, Hullings et al determined that older adults in the highest quintile of cereal fiber intake had significantly lower odds of CRC than those in lower odds for CRC when compared with lowest quintile (OR, 0.89 [95% CI, 0.83- 0.96]; P < .001).⁴⁴ These findings support existing guidance that prioritizes whole grains as a key source of dietary fiber for CRC prevention.

A recent literature review on fiber, fat, and CRC risk suggested a consensus regarding one protective mechanism: dietary fiber from grains modulates the gut microbiota by promoting butyrate synthesis.⁴⁵ Butyrate is a short-chain fatty acid that supports energy production in colonocytes and has tumor-suppressing properties.⁴⁶ Our findings suggest there could be more to learn about the relationship between butyrate production and reduction of CRC risk through metabolomic studies that use measurements of plasma butyrate. These studies may examine associations between not just a singular food or food category, but rather food patterns that include fruits, vegetables, nuts and seeds, and whole grains known to promote butyrate production and plasma butyrate.⁴⁷

Improved understanding of mechanisms and risk-modifying lifestyle factors such as dietary patterns may enhance prevention strategies. Identifying the collective chemopreventive characteristics of a specific dietary pattern (eg, MD) will be helpful to clinicians and health care staff to promote healthy eating to reduce cancer risk. More studies are needed to understand whether such promotion is more clinically applicable and effective for patients, as compared with eating more or less of specific foods (eg, more whole grains, less red meat). Furthermore, considering important environmental factors collectively beyond dietary patterns may offer a way to better tailor screening and implement a variety of lifestyle interventions. In the literature, this is often referred to as a teachable moment when patients’ attentions are captured and may position them to be more receptive to guidance.⁴⁸

Limitations

This study has several important limitations and leaves opportunities for future studies that explore the role of dietary patterns and AN or CRC risk. First, the FFQ data used to calculate dietary pattern scores used in analysis were only captured at baseline, and there are nearly 3 decades across the study period. However, it is widely assumed that the diets of older adults, like those included in this study, remain stable over time which is appropriate given our sample population was aged 50 to 75 years when the baseline FFQ data were collected.^49-51 Additionally, while the HEI is a well-documented, standard scoring method for dietary quality, there are multitudes of dietary pattern scoring approaches for MD and DASH.^23,52,53 Finally, findings from this study using the sample of veterans may not be generalizable to a broader population. Future longitudinal studies that test for a clinically significant change threshold are warranted.

Conclusion

Results of this study suggest future research should further explore the effects of dietary patterns, particularly intake of specific food groups in combination, as opposed to individual nutrients or food items, on AN and CRC risk. Possible studies might explore these dietary patterns for their mechanistic role in altering the microbiome metabolism, which may influence CRC outcomes or include diet in a more comprehensive, holistic risk score that could be used to predict colonic neoplasia risk or in intervention studies that assess the effects of dietary changes on long-term CRC prevention. We suggest there are differences in people’s dietary intake patterns that might be important to consider when implementing tailored approaches to CRC risk mitigation.

Screening for colorectal cancer (CRC) with colonoscopy enables the identification and removal of CRC precursors (colonic adenomas) and has been associated with reduced risk of CRC incidence and mortality.^1-3 Furthermore, there is consensus that diet and lifestyle may be associated with forestalling CRC pathogenesis at the intermediate adenoma stages.^4-7 However, studies have shown that US veterans have poorer diet quality and a higher risk for neoplasia compared with nonveterans, reinforcing the need for tailored clinical approaches.^8,9 Combining screening with conversations about modifiable environmental and lifestyle risk factors, such as poor diet, is a highly relevant and possibly easily leveraged prevention for those at high risk. However, there is limited evidence for any particular dietary patterns or dietary features that are most important over time.⁷

Several dietary components have been shown to be associated with CRC risk,10 either as potentially chemopreventive (fiber, fruits and vegetables,¹¹ dairy,¹² supplemental vitamin D,¹³ calcium,¹⁴ and multivitamins¹⁵) or carcinogenic (red meat¹⁶ and alcohol¹⁷). Previous studies of veterans have similarly shown that higher intake of fiber and vitamin D reduced risk, and red meat is associated with an increased risk for finding CRC precursors during colonoscopy.¹⁸ However, these dietary categories are often analyzed in isolation. Studying healthy dietary patterns in aggregate may be more clinically relevant and easier to implement for prevention of CRC and its precursors.^19-21 Healthy dietary patterns, such as the US Dietary Guidelines for Americans represented by the Healthy Eating Index (HEI), the Mediterranean diet (MD), and the Dietary Approaches to Stop Hypertension (DASH) diet, have been associated with lower risk for chronic disease.^22-24 Despite the extant literature, no known studies have compared these dietary patterns for associations with risk of CRC precursor or CRC development among US veterans undergoing long-term screening and follow-up after a baseline colonoscopy.

The objective of this study was to test for associations between baseline scores of healthy dietary patterns and the most severe colonoscopy findings (MSCFs) over ≥ 10 years following a baseline screening colonoscopy in veterans.

Methods

Participants in the Cooperative Studies Program (CSP) #380 cohort study included 3121 asymptomatic veterans aged 50 to 75 years at baseline who had consented to initial screening colonoscopy between 1994 and 1997, with subsequent follow-up and surveillance.²⁵ Prior to their colonoscopy, all participants completed a baseline study survey that included questions about cancer risk factors including family history of CRC, diet, physical activity, and medication use.

Included in this cross-sectional analysis were data from a sample of veteran participants of the CSP #380 cohort with 1 baseline colonoscopy, follow-up surveillance through 2009, a cancer risk factor survey collected at baseline, and complete demographic and clinical indicator data. Excluded from the analysis were 67 participants with insufficient responses to the dietary food frequency questionnaire (FFQ) and 31 participants with missing body mass index (BMI), 3023 veterans.

Measures

MSCF. The outcome of interest in this study was the MSCF recorded across all participant colonoscopies during the study period. MSCF was categorized as either (1) no neoplasia; (2) < 2 nonadvanced adenomas, including small adenomas (diameter < 10 mm) with tubular histology; or (3) advanced neoplasia (AN), which is characterized by adenomas > 10 mm in diameter, with villous histology, with high-grade dysplasia, or CRC.

Dietary patterns. Dietary pattern scores representing dietary quality and calculated based on recommendations of the US Dietary Guidelines for Americans using the HEI, MD, and DASH diets were independent variables.^26-28 These 3 dietary patterns were chosen for their hypothesized relationship with CRC risk, but each weighs food categories differently (Appendix 1).^22-24,29 Dietary pattern scores were calculated using the CSP #380 self-reported responses to 129 baseline survey questions adapted from a well-established and previously validated semiquantitative FFQ.³⁰ The form was administered by mail twice to a sample of 127 participants at baseline and at 1 year. During this interval, men completed 1-week diet records twice, spaced about 6 months apart. Mean values for intake of most nutrients assessed by the 2 methods were similar. Intraclass correlation coefficients for the baseline and 1-year FFQ-assessed nutrient intakes that ranged from 0.47 for vitamin E (without supplements) to 0.80 for vitamin C (with supplements). Correlation coefficients between the energy-adjusted nutrient intakes were measured by diet records and the 1-year FFQ, which asked about diet during the year encompassing the diet records. Higher raw and percent scores indicated better alignment with recommendations from each respective dietary pattern. Percent scores were calculated as a standardizing method and used in analyses for ease of comparing the dietary patterns. Scoring can be found in Appendix 2.

Demographic characteristics and clinical indicators. Demographic characteristics included age categories, sex, and race/ethnicity. Clinical indicators included BMI, the number of comorbid conditions used to calculate the Charlson Comorbidity Index, family history of CRC in first-degree relatives, number of follow-up colonoscopies across the study period, and food-based vitamin D intake.³¹ These variables were chosen for their applicability found in previous CSP #380 cohort studies.^18,32,33 Self-reported race and ethnicity were collapsed due to small numbers in some groups. The authors acknowledge these are distinct concepts and the variable has limited utility other than for controlling for systemic racism in the model.

Statistical Analyses

Descriptive statistics were used to describe distributional assumptions for all variables, including demographics, clinical indicators, colonoscopy results, and dietary patterns. Pairwise correlations between the total dietary pattern scores and food category scores were calculated with Pearson correlation (r).

Multinomial logistic regression models were created using SAS procedure LOGISTIC with the outcome of the categorical MSCF (no neoplasia, nonadvanced adenoma, or AN).³⁴ A model was created for each independent predictor variable of interest (ie, the HEI, MD, or DASH percentage-standardized dietary pattern score and each food category comprising each dietary pattern score). All models were adjusted for age, sex, race/ethnicity, BMI, number of comorbidities, family history of CRC, number of follow-up colonoscopies, and estimated daily food-derived vitamin D intake. The demographic and clinical indicators were included in the models as they are known to be associated with CRC risk.¹⁸ The number of colonoscopies was included to control for surveillance intensity presuming risk for AN is reduced as polyps are removed. Because colonoscopy findings from an initial screening have unique clinical implications compared with follow- up and surveillance, MSCF was observed in 2 ways in sensitivity analyses: (1) baseline and (2) aggregate follow-up and surveillance only, excluding baseline findings.

Adjusted odds ratios (aORs) and 95% CIs for each of the MSCF outcomes with a reference finding of no neoplasia for the models are presented. We chose not to adjust for multiple comparisons across the different dietary patterns given the correlation between dietary pattern total and category scores but did adjust for multiple comparisons for dietary categories within each dietary pattern. Tests for statistical significance used α= .05 for the dietary pattern total scores and P values for the dietary category scores for each dietary pattern controlled for false discovery rate using the MULTTEST SAS procedure.35 All data manipulations and analyses were performed using SAS version 9.4.

Results

The study included 3023 patients. All were aged 50 to 75 years, 2923 (96.7%) were male and 2532 (83.8%) were non-Hispanic White (Table 1). Most participants were overweight or obese (n = 2535 [83.8%]), 2024 (67.0%) had ≤ 2 comorbidities, and 2602 (86.1%) had no family history of CRC. The MSCF for 1628 patients (53.9%) was no neoplasia, 966 patients (32.0%) was nonadvanced adenoma, and 429 participants (14.2%) had AN.

Mean percent scores were 58.5% for HEI, 38.2% for MD, and 63.1% for the DASH diet, with higher percentages indicating greater alignment with the recommendations for each diet (Table 2). All 3 dietary patterns scores standardized to percentages were strongly and significantly correlated in pairwise comparisons: HEI:MD, r = 0.62 (P < .001); HEI:DASH, r = 0.60 (P < .001); and MD:DASH, r = 0.72 (P < .001). Likewise, food category scores were significantly correlated across dietary patterns. For example, whole grain and fiber values from each dietary score were strongly correlated in pairwise comparisons: HEI Whole Grain:MD Grain, r = 0.64 (P < .001); HEI Whole Grain:DASH Fiber, r = 0.71 (P < .001); and MD Grain:DASH Fiber, r = 0.70 (P < .001).

Associations between individual participants' dietary pattern scores and the outcome of their pooled MSCF from baseline screening and ≥ 10 years of surveillance are presented in Table 3. For each single-point increases in dietary pattern scores (reflecting better dietary quality), aORs for nonadvanced adenoma vs no neoplasia were slightly lower but not statistically significantly: HEI, aOR, 1.00 (95% CI, 0.99-1.01); MD, aOR, 0.98 (95% CI, 0.94-1.02); and DASH, aOR, 0.99 (95% CI, 0.99-1.00). aORs for AN vs no neoplasia were slightly lower for each dietary pattern assessed, and only the MD and DASH scores were significantly different from 1.00: HEI, aOR, 1.00 (95% CI, 0.99-1.01); MD, aOR, 0.95 (95% CI, 0.90-1.00); and DASH, aOR, 0.99 (95% CI, 0.98-1.00).

We observed lower odds for nonadvanced adenoma and AN among all these dietary patterns when there was greater alignment with the recommended intake of whole grains and fiber. In separate models conducted using food categories comprising the dietary patterns as independent variables and after correcting for multiple tests, higher scores for the HEI Refined Grain category were associated with higher odds for nonadvanced adenoma (aOR, 1.03 [95% CI, 1.01-1.05]; P = .01) and AN (aOR, 1.05 [95% CI, 1.02-1.08]; P < .001). Higher scores for the HEI Whole Grain category were associated with lower odds for nonadvanced adenoma (aOR, 0.97 [95% CI, 0.95-0.99]; P = .01) and AN (aOR, 0.96 [95% CI, 0.93-0.99]; P = .01). Higher scores for the MD Grain category were significantly associated with lower odds for nonadvanced adenoma (aOR, 0.44 [95% CI, 0.26-0.75]; P = .002) and AN (aOR, 0.29 [95% CI, 0.14-0.62]; P = .001). The DASH Grains category also was significantly associated with lower odds for AN (aOR, 0.86 [95% CI, 0.78-0.95]; P = .002).

Discussion

In this study of 3023 veterans undergoing first-time screening colonoscopy and ≥ 10 years of surveillance, we found that healthy dietary patterns, as assessed by the MD and DASH diet, were significantly associated with lower risk of AN. Additionally, we identified lower odds for AN and nonadvanced adenoma compared with no neoplasia for higher grain scores for all the dietary patterns studied. Other food categories that comprise the dietary pattern scores had mixed associations with the MSCF outcomes. Several other studies have examined associations between dietary patterns and risk for CRC but to our knowledge, no studies have explored these associations among US veterans.

These results also indicate study participants had better than average (based on a 50% threshold) dietary quality according to the HEI and DASH diet scoring methods we used, but poor dietary quality according to the MD scoring method. The mean HEI scores for the present study were higher than a US Department of Agriculture study by Dong et al that compared dietary quality between veterans and nonveterans using the HEI, for which veterans’ expected HEI score was 45.6 of 100.⁸ This could be explained by the fact that the participants needed to be healthy to be eligible and those with healthier behaviors overall may have self-selected into the study due to motivation for screening during a time when screening was not yet commonplace. ³⁶ Similarly, participants of the present study had higher adherence to the DASH diet (63.1%) than adolescents with diabetes in a study by Günther et al. Conversely, firefighters who were coached to use a Mediterranean-style dietary pattern and dietary had higher adherence to MD than did participants in this study.²⁷

A closer examination of specific food category component scores that comprise the 3 distinct dietary patterns revealed mixed results from the multinomial modeling, which may have to do with the guideline thresholds used to calculate the dietary scores. When analyzed separately in the logistic regression models for their associations with nonadvanced adenomas and AN compared with no neoplasia, higher MD and DASH fruit scores (but not HEI fruit scores) were found to be significant. Other studies have had mixed findings when attempting to test for associations of fruit intake with adenoma recurrence.^10,37

This study had some unexpected findings. Vegetable intake was not associated with nonadvanced adenomas or AN risk. Studies of food categories have consistently found vegetable (specifically cruciferous ones) intake to be linked with lower odds for cancers.³⁸ Likewise, the red meat category, which was only a unique food category in the MD score, was not associated with nonadvanced adenomas or AN. Despite consistent literature suggesting higher intake of red meat and processed meats increases CRC risk, in 2019 the Nutritional Recommendations Consortium indicated that the evidence was weak.^39,40 This study showed higher DASH diet scores for low-fat dairy, which were maximized when participants reported at least 50% of their dairy servings per day as being low-fat, had lower odds for AN. Yet, the MD scores for low-fat dairy had no association with either outcome; their calculation was based on total number of servings per week. This difference in findings suggests the fat intake ratio may be more relevant to CRC risk than intake quantity.

The literature is mixed regarding fatty acid intake and CRC risk, which may be relevant to both dairy and meat intake. One systematic review and meta-analysis found dietary fat and types of fatty acid intake had no association with CRC risk.⁴¹ However, a more recent meta-analysis that assessed both dietary intake and plasma levels of fatty acids did find some statistically significant differences for various types of fatty acids and CRC risk.⁴²

The findings in the present study that grain intake is associated with lower odds for more severe colonoscopy findings among veterans are notable.⁴³ Lieberman et al, using the CSP #380 data, found that cereal fiber intake was associated with a lower odds for AN compared with hyperplastic polyps (OR, 0.98 [95% CI, 0.96- 1.00]).¹⁸ Similarly, Hullings et al determined that older adults in the highest quintile of cereal fiber intake had significantly lower odds of CRC than those in lower odds for CRC when compared with lowest quintile (OR, 0.89 [95% CI, 0.83- 0.96]; P < .001).⁴⁴ These findings support existing guidance that prioritizes whole grains as a key source of dietary fiber for CRC prevention.

A recent literature review on fiber, fat, and CRC risk suggested a consensus regarding one protective mechanism: dietary fiber from grains modulates the gut microbiota by promoting butyrate synthesis.⁴⁵ Butyrate is a short-chain fatty acid that supports energy production in colonocytes and has tumor-suppressing properties.⁴⁶ Our findings suggest there could be more to learn about the relationship between butyrate production and reduction of CRC risk through metabolomic studies that use measurements of plasma butyrate. These studies may examine associations between not just a singular food or food category, but rather food patterns that include fruits, vegetables, nuts and seeds, and whole grains known to promote butyrate production and plasma butyrate.⁴⁷

Improved understanding of mechanisms and risk-modifying lifestyle factors such as dietary patterns may enhance prevention strategies. Identifying the collective chemopreventive characteristics of a specific dietary pattern (eg, MD) will be helpful to clinicians and health care staff to promote healthy eating to reduce cancer risk. More studies are needed to understand whether such promotion is more clinically applicable and effective for patients, as compared with eating more or less of specific foods (eg, more whole grains, less red meat). Furthermore, considering important environmental factors collectively beyond dietary patterns may offer a way to better tailor screening and implement a variety of lifestyle interventions. In the literature, this is often referred to as a teachable moment when patients’ attentions are captured and may position them to be more receptive to guidance.⁴⁸

Limitations

This study has several important limitations and leaves opportunities for future studies that explore the role of dietary patterns and AN or CRC risk. First, the FFQ data used to calculate dietary pattern scores used in analysis were only captured at baseline, and there are nearly 3 decades across the study period. However, it is widely assumed that the diets of older adults, like those included in this study, remain stable over time which is appropriate given our sample population was aged 50 to 75 years when the baseline FFQ data were collected.^49-51 Additionally, while the HEI is a well-documented, standard scoring method for dietary quality, there are multitudes of dietary pattern scoring approaches for MD and DASH.^23,52,53 Finally, findings from this study using the sample of veterans may not be generalizable to a broader population. Future longitudinal studies that test for a clinically significant change threshold are warranted.

Conclusion

Results of this study suggest future research should further explore the effects of dietary patterns, particularly intake of specific food groups in combination, as opposed to individual nutrients or food items, on AN and CRC risk. Possible studies might explore these dietary patterns for their mechanistic role in altering the microbiome metabolism, which may influence CRC outcomes or include diet in a more comprehensive, holistic risk score that could be used to predict colonic neoplasia risk or in intervention studies that assess the effects of dietary changes on long-term CRC prevention. We suggest there are differences in people’s dietary intake patterns that might be important to consider when implementing tailored approaches to CRC risk mitigation.

Can exercise “therapy” and diet improve survival in patients with colon cancer? It appears so, according to two pivotal studies presented at American Society of Clinical Oncology (ASCO) 2025 annual meeting.

In the CHALLENGE trial, a structured exercise program after surgery and adjuvant chemotherapy cut the risk for colon cancer recurrence in patients with stage III and high-risk stage II disease by more than one quarter and the risk for death by more than one third.

“The magnitude of benefit with exercise is substantial. In fact, it is comparable, and in some cases exceeds the magnitude of benefit of many of our very good standard medical therapies in oncology,” study presenter Christopher Booth, MD, with Queen’s University, Kingston, Ontario, Canada, told attendees.

Results of the study were published online in The New England Journal of Medicine to coincide with the presentation at the meeting.

The findings are “nothing short of a major milestone,” said study discussant Peter Campbell, PhD, with Montefiore Einstein Comprehensive Cancer Center, Bronx, New York.

The other study showed that eating a less inflammatory diet may reduce the risk for death in patients with colon cancer, with the greatest benefits seen in those who embraced anti-inflammatory foods and exercised regularly.

“Putting these two abstracts into perspective, we as physicians need to be essentially prescribing healthy diet and exercise. The combination of the two are synergistic,” Julie Gralow, MD, ASCO chief medical officer and executive vice president, told attendees.

Despite the benefits of these lifestyle changes, exercise and diet are meant to supplement, not replace, established colon cancer treatments.

It would be a false binary to frame this as lifestyle vs cancer treatment, explained Mark Lewis, MD, director of Gastrointestinal Oncology at Intermountain Healthcare in Salt Lake City, Utah. With exercise, for instance, “the key is giving enough chemo to protect against recurrence and eliminate micrometastases but not so much that we cause neuropathy and reduce function and ability to follow the CHALLENGE structured program,” Lewis said.

Exercise and Survival

Colon cancer remains the second-leading cause of cancer death worldwide. Even with surgery and chemotherapy, roughly 30% of patients with stage III and high-risk stage II colon cancer will experience disease recurrence.

“As oncologists, one of the most common questions we get asked by patients is — what else can I do to improve my outcome?” Booth said.

Observational studies published nearly two decades ago hinted that physically active cancer survivors fare better, but no randomized trial has definitively tested whether exercise could alter disease course. That knowledge gap prompted the Canadian Cancer Trials Group to launch the CHALLENGE trial.

Between 2009 and 2023, the phase 3 study enrolled 889 adults (median age, 61 years; 51% women) who had completed surgery and adjuvant chemotherapy for stage III (90%) or high-risk stage II (10%) colon cancer. Most patients were from Canada and Australia and were enrolled 2-6 months after completing chemotherapy.

Half of study participants were randomly allocated to a structured exercise program (n = 445) and half to receive standard health education materials promoting physical activity and healthy eating (control individuals, n = 444).

As part of the structured exercise intervention, patients met with a physical activity consultant twice a month for the first 6 months. These sessions included exercise coaching and supervised exercise. Patients could choose their preferred aerobic exercise and most picked brisk walking.

The consultants gave each patient an “exercise prescription” to hit a specific amount of exercise. The target was an additional 10 metabolic equivalent (MET)–hours of aerobic activity per week — about three to four brisk walks each lasting 45-60 minutes. After 6 months, patients met with their consultants once a month, with additional sessions available for extra support if needed.

Structured exercise led to “substantial and sustained” increases in the amount of exercise participants did, as well as physiologic measures of their fitness, with “highly relevant” improvements in VO₂ max, 6-minute walk test, and patient-reported physical function, underscoring that participants were not only exercising more but also getting fitter, Booth said.

Exercise was associated with a clinically meaningful and statistically significant 28% reduction in the risk for recurrent or new cancer (hazard ratio [HR], 0.72; P = .017), with a 5-year disease free survival rate of 80% in the exercise group and 74% in the control group.

In other words, “for every 16 patients that went on the exercise program, exercise prevented 1 person from recurrent or new cancer” at 5 years, Booth reported.

Overall survival results were “even more impressive,” he said.

At 8 years, 90% of patients in the exercise program were alive vs 83% of those in the control group, which translated to a 37% lower risk for death (HR, 0.63; P = .022).

“For every 14 patients who went on the exercise program, exercise prevented 1 person from dying” at the 8-year mark, Booth noted.

“Notably, this difference in survival was not driven by difference in cardiovascular deaths but by a reduction in the risk of death from colon cancer,” he said.

Besides a slight uptick in musculoskeletal aches, no major safety signals emerged in the exercise group.

It’s important to note that the survival benefit associated with exercise came after patients had received surgery followed by chemotherapy — in other words, exercise did not replace established cancer treatments. It’s also unclear whether initiating an exercise intervention earlier in the treatment trajectory — before surgery or during chemotherapy, instead of after chemotherapy — could further improve cancer outcomes, the authors noted.

Still, “exercise as an intervention is a no brainer and should be implemented broadly,” said ASCO expert Pamela Kunz, MD, with Yale School of Medicine, New Haven, Connecticut.

Marco Gerlinger, MD, with Barts Cancer Institute, London, England, agreed.

“Oncologists can now make a very clear evidence-based recommendation for patients who just completed their chemotherapy for bowel cancer and are fit enough for such an exercise program,” Gerlinger said in a statement from the nonprofit UK Science Media Centre.

Booth noted that knowledge alone will not be sufficient to allow most patients to change their lifestyle and realize the health benefits.

“The policy implementation piece of this is really key, and we need health systems, hospitals, and payers to invest in these behavior support programs so that patients have access to a physical activity consultant and can realize the health benefits,” he said.

“This intervention is empowering and achievable for patients and with much, much lower cost than many of our therapies. It is also sustainable for health systems,” he concluded.

Diet and Survival

Diet can also affect outcomes in patients with colon cancer.

In the same session describing the CHALLENGE results, Sara Char, MD, with Dana-Farber Cancer Institute in Boston, reported findings showing that consuming a diet high in proinflammatory foods was associated with worse overall survival in patients with stage III colon cancer. A proinflammatory diet includes red and processed meats, sugary drinks, and refined grains, while an anti-inflammatory diet focuses on fruits, vegetables, whole grains, fish, and olive oil.

Chronic systemic inflammation has been implicated in both colon cancer development and in its progression, and elevated levels of inflammatory markers in the blood have previously been associated with worse survival outcomes in patients with stage III colon cancer.

Char and colleagues analyzed dietary patterns of a subset of 1625 patients (mean age, 61 years) with resected stage III colon cancer enrolled in the phase 3 CALGB/SWOG 80702 (Alliance) clinical trial, which compared 3 months of adjuvant chemotherapy with 6 months of adjuvant chemotherapy, with or without the anti-inflammatory medication celecoxib.

As part of the trial, participants reported their diet and exercise habits at various timepoints. Their diets were scored using the validated empirical dietary inflammatory pattern (EDIP) tool, which is a weighted sum of 18 food groups — nine proinflammatory and nine anti-inflammatory. A high EDIP score marks a proinflammatory diet, and a low EDIP score indicates a less inflammatory diet.

During median follow-up of nearly 4 years, researchers noted a trend toward worse disease-free survival in patients with high proinflammatory diets (HR, 1.46), but this association was not significant in the multivariable adjusted model (HR, 1.36; P = .22), Char reported.

However, higher intake of proinflammatory foods was associated with significantly worse overall survival.

Patients who consumed the most proinflammatory foods (top 20%) had an 87% higher risk for death compared with those who consumed the least (bottom 20%; HR, 1.87). The median overall survival in the highest quintile was 7.7 years and was not reached in the lowest quintile.

Combine Exercise and Diet for Best Results

To examine the joint effect of physical activity and diet on overall survival, patients were divided into higher and lower levels of physical activity using a cut-off of 9 MET hours per week, which roughly correlates to 30 minutes of vigorous walking five days a week with a little bit of light yoga, Char explained.

In this analysis, patients with less proinflammatory diets and higher physical activity levels had the best overall survival outcomes, with a 63% lower risk for death compared with peers who consumed more pro-inflammatory diets and exercised less (HR, 0.37; P < .0001).

Daily celecoxib use and low-dose aspirin use (< 100 mg/d) did not affect the association between inflammatory diet and survival.

Char cautioned, that while the EDIP tool is useful to measure the inflammatory potential of a diet, “this is not a dietary recommendation, and we need further studies to be able to tailor our findings into dietary recommendations that can be provided to patients at the bedside.”

Gralow said this “early but promising observational study suggests a powerful synergy: Patients with stage III colon cancer who embraced anti-inflammatory foods and exercised regularly showed the best overall survival compared to those with inflammatory diets and limited exercise.”

The CHALLENGE trial was funded by the Canadian Cancer Society, the National Health and Medical Research Council, Cancer Research UK, and the University of Sydney Cancer Research Fund. Booth had no disclosures. The diet study was funded by the National Institutes of Health, Pfizer, and the Project P Fund. Char disclosed an advisory/consultant role with Goodpath. Kunz, Gralow and Campbell had no relevant disclosures.

A version of this article first appeared on Medscape.com.

Can exercise “therapy” and diet improve survival in patients with colon cancer? It appears so, according to two pivotal studies presented at American Society of Clinical Oncology (ASCO) 2025 annual meeting.

In the CHALLENGE trial, a structured exercise program after surgery and adjuvant chemotherapy cut the risk for colon cancer recurrence in patients with stage III and high-risk stage II disease by more than one quarter and the risk for death by more than one third.

“The magnitude of benefit with exercise is substantial. In fact, it is comparable, and in some cases exceeds the magnitude of benefit of many of our very good standard medical therapies in oncology,” study presenter Christopher Booth, MD, with Queen’s University, Kingston, Ontario, Canada, told attendees.

Results of the study were published online in The New England Journal of Medicine to coincide with the presentation at the meeting.

The findings are “nothing short of a major milestone,” said study discussant Peter Campbell, PhD, with Montefiore Einstein Comprehensive Cancer Center, Bronx, New York.

The other study showed that eating a less inflammatory diet may reduce the risk for death in patients with colon cancer, with the greatest benefits seen in those who embraced anti-inflammatory foods and exercised regularly.

“Putting these two abstracts into perspective, we as physicians need to be essentially prescribing healthy diet and exercise. The combination of the two are synergistic,” Julie Gralow, MD, ASCO chief medical officer and executive vice president, told attendees.

Despite the benefits of these lifestyle changes, exercise and diet are meant to supplement, not replace, established colon cancer treatments.

It would be a false binary to frame this as lifestyle vs cancer treatment, explained Mark Lewis, MD, director of Gastrointestinal Oncology at Intermountain Healthcare in Salt Lake City, Utah. With exercise, for instance, “the key is giving enough chemo to protect against recurrence and eliminate micrometastases but not so much that we cause neuropathy and reduce function and ability to follow the CHALLENGE structured program,” Lewis said.

Exercise and Survival

Colon cancer remains the second-leading cause of cancer death worldwide. Even with surgery and chemotherapy, roughly 30% of patients with stage III and high-risk stage II colon cancer will experience disease recurrence.

“As oncologists, one of the most common questions we get asked by patients is — what else can I do to improve my outcome?” Booth said.

Observational studies published nearly two decades ago hinted that physically active cancer survivors fare better, but no randomized trial has definitively tested whether exercise could alter disease course. That knowledge gap prompted the Canadian Cancer Trials Group to launch the CHALLENGE trial.

Between 2009 and 2023, the phase 3 study enrolled 889 adults (median age, 61 years; 51% women) who had completed surgery and adjuvant chemotherapy for stage III (90%) or high-risk stage II (10%) colon cancer. Most patients were from Canada and Australia and were enrolled 2-6 months after completing chemotherapy.

Half of study participants were randomly allocated to a structured exercise program (n = 445) and half to receive standard health education materials promoting physical activity and healthy eating (control individuals, n = 444).

As part of the structured exercise intervention, patients met with a physical activity consultant twice a month for the first 6 months. These sessions included exercise coaching and supervised exercise. Patients could choose their preferred aerobic exercise and most picked brisk walking.

The consultants gave each patient an “exercise prescription” to hit a specific amount of exercise. The target was an additional 10 metabolic equivalent (MET)–hours of aerobic activity per week — about three to four brisk walks each lasting 45-60 minutes. After 6 months, patients met with their consultants once a month, with additional sessions available for extra support if needed.

Structured exercise led to “substantial and sustained” increases in the amount of exercise participants did, as well as physiologic measures of their fitness, with “highly relevant” improvements in VO₂ max, 6-minute walk test, and patient-reported physical function, underscoring that participants were not only exercising more but also getting fitter, Booth said.

Exercise was associated with a clinically meaningful and statistically significant 28% reduction in the risk for recurrent or new cancer (hazard ratio [HR], 0.72; P = .017), with a 5-year disease free survival rate of 80% in the exercise group and 74% in the control group.

In other words, “for every 16 patients that went on the exercise program, exercise prevented 1 person from recurrent or new cancer” at 5 years, Booth reported.

Overall survival results were “even more impressive,” he said.

At 8 years, 90% of patients in the exercise program were alive vs 83% of those in the control group, which translated to a 37% lower risk for death (HR, 0.63; P = .022).

“For every 14 patients who went on the exercise program, exercise prevented 1 person from dying” at the 8-year mark, Booth noted.

“Notably, this difference in survival was not driven by difference in cardiovascular deaths but by a reduction in the risk of death from colon cancer,” he said.

Besides a slight uptick in musculoskeletal aches, no major safety signals emerged in the exercise group.

It’s important to note that the survival benefit associated with exercise came after patients had received surgery followed by chemotherapy — in other words, exercise did not replace established cancer treatments. It’s also unclear whether initiating an exercise intervention earlier in the treatment trajectory — before surgery or during chemotherapy, instead of after chemotherapy — could further improve cancer outcomes, the authors noted.

Still, “exercise as an intervention is a no brainer and should be implemented broadly,” said ASCO expert Pamela Kunz, MD, with Yale School of Medicine, New Haven, Connecticut.

Marco Gerlinger, MD, with Barts Cancer Institute, London, England, agreed.

“Oncologists can now make a very clear evidence-based recommendation for patients who just completed their chemotherapy for bowel cancer and are fit enough for such an exercise program,” Gerlinger said in a statement from the nonprofit UK Science Media Centre.

Booth noted that knowledge alone will not be sufficient to allow most patients to change their lifestyle and realize the health benefits.

“The policy implementation piece of this is really key, and we need health systems, hospitals, and payers to invest in these behavior support programs so that patients have access to a physical activity consultant and can realize the health benefits,” he said.

“This intervention is empowering and achievable for patients and with much, much lower cost than many of our therapies. It is also sustainable for health systems,” he concluded.

Diet and Survival

Diet can also affect outcomes in patients with colon cancer.

In the same session describing the CHALLENGE results, Sara Char, MD, with Dana-Farber Cancer Institute in Boston, reported findings showing that consuming a diet high in proinflammatory foods was associated with worse overall survival in patients with stage III colon cancer. A proinflammatory diet includes red and processed meats, sugary drinks, and refined grains, while an anti-inflammatory diet focuses on fruits, vegetables, whole grains, fish, and olive oil.

Chronic systemic inflammation has been implicated in both colon cancer development and in its progression, and elevated levels of inflammatory markers in the blood have previously been associated with worse survival outcomes in patients with stage III colon cancer.

Char and colleagues analyzed dietary patterns of a subset of 1625 patients (mean age, 61 years) with resected stage III colon cancer enrolled in the phase 3 CALGB/SWOG 80702 (Alliance) clinical trial, which compared 3 months of adjuvant chemotherapy with 6 months of adjuvant chemotherapy, with or without the anti-inflammatory medication celecoxib.

As part of the trial, participants reported their diet and exercise habits at various timepoints. Their diets were scored using the validated empirical dietary inflammatory pattern (EDIP) tool, which is a weighted sum of 18 food groups — nine proinflammatory and nine anti-inflammatory. A high EDIP score marks a proinflammatory diet, and a low EDIP score indicates a less inflammatory diet.

During median follow-up of nearly 4 years, researchers noted a trend toward worse disease-free survival in patients with high proinflammatory diets (HR, 1.46), but this association was not significant in the multivariable adjusted model (HR, 1.36; P = .22), Char reported.

However, higher intake of proinflammatory foods was associated with significantly worse overall survival.

Patients who consumed the most proinflammatory foods (top 20%) had an 87% higher risk for death compared with those who consumed the least (bottom 20%; HR, 1.87). The median overall survival in the highest quintile was 7.7 years and was not reached in the lowest quintile.

Combine Exercise and Diet for Best Results

To examine the joint effect of physical activity and diet on overall survival, patients were divided into higher and lower levels of physical activity using a cut-off of 9 MET hours per week, which roughly correlates to 30 minutes of vigorous walking five days a week with a little bit of light yoga, Char explained.

In this analysis, patients with less proinflammatory diets and higher physical activity levels had the best overall survival outcomes, with a 63% lower risk for death compared with peers who consumed more pro-inflammatory diets and exercised less (HR, 0.37; P < .0001).

Daily celecoxib use and low-dose aspirin use (< 100 mg/d) did not affect the association between inflammatory diet and survival.

Char cautioned, that while the EDIP tool is useful to measure the inflammatory potential of a diet, “this is not a dietary recommendation, and we need further studies to be able to tailor our findings into dietary recommendations that can be provided to patients at the bedside.”

Gralow said this “early but promising observational study suggests a powerful synergy: Patients with stage III colon cancer who embraced anti-inflammatory foods and exercised regularly showed the best overall survival compared to those with inflammatory diets and limited exercise.”

The CHALLENGE trial was funded by the Canadian Cancer Society, the National Health and Medical Research Council, Cancer Research UK, and the University of Sydney Cancer Research Fund. Booth had no disclosures. The diet study was funded by the National Institutes of Health, Pfizer, and the Project P Fund. Char disclosed an advisory/consultant role with Goodpath. Kunz, Gralow and Campbell had no relevant disclosures.

A version of this article first appeared on Medscape.com.

Can exercise “therapy” and diet improve survival in patients with colon cancer? It appears so, according to two pivotal studies presented at American Society of Clinical Oncology (ASCO) 2025 annual meeting.

In the CHALLENGE trial, a structured exercise program after surgery and adjuvant chemotherapy cut the risk for colon cancer recurrence in patients with stage III and high-risk stage II disease by more than one quarter and the risk for death by more than one third.

“The magnitude of benefit with exercise is substantial. In fact, it is comparable, and in some cases exceeds the magnitude of benefit of many of our very good standard medical therapies in oncology,” study presenter Christopher Booth, MD, with Queen’s University, Kingston, Ontario, Canada, told attendees.

Results of the study were published online in The New England Journal of Medicine to coincide with the presentation at the meeting.

The findings are “nothing short of a major milestone,” said study discussant Peter Campbell, PhD, with Montefiore Einstein Comprehensive Cancer Center, Bronx, New York.

The other study showed that eating a less inflammatory diet may reduce the risk for death in patients with colon cancer, with the greatest benefits seen in those who embraced anti-inflammatory foods and exercised regularly.

“Putting these two abstracts into perspective, we as physicians need to be essentially prescribing healthy diet and exercise. The combination of the two are synergistic,” Julie Gralow, MD, ASCO chief medical officer and executive vice president, told attendees.

Despite the benefits of these lifestyle changes, exercise and diet are meant to supplement, not replace, established colon cancer treatments.

It would be a false binary to frame this as lifestyle vs cancer treatment, explained Mark Lewis, MD, director of Gastrointestinal Oncology at Intermountain Healthcare in Salt Lake City, Utah. With exercise, for instance, “the key is giving enough chemo to protect against recurrence and eliminate micrometastases but not so much that we cause neuropathy and reduce function and ability to follow the CHALLENGE structured program,” Lewis said.

Exercise and Survival

Colon cancer remains the second-leading cause of cancer death worldwide. Even with surgery and chemotherapy, roughly 30% of patients with stage III and high-risk stage II colon cancer will experience disease recurrence.

“As oncologists, one of the most common questions we get asked by patients is — what else can I do to improve my outcome?” Booth said.

Observational studies published nearly two decades ago hinted that physically active cancer survivors fare better, but no randomized trial has definitively tested whether exercise could alter disease course. That knowledge gap prompted the Canadian Cancer Trials Group to launch the CHALLENGE trial.

Between 2009 and 2023, the phase 3 study enrolled 889 adults (median age, 61 years; 51% women) who had completed surgery and adjuvant chemotherapy for stage III (90%) or high-risk stage II (10%) colon cancer. Most patients were from Canada and Australia and were enrolled 2-6 months after completing chemotherapy.

Half of study participants were randomly allocated to a structured exercise program (n = 445) and half to receive standard health education materials promoting physical activity and healthy eating (control individuals, n = 444).

As part of the structured exercise intervention, patients met with a physical activity consultant twice a month for the first 6 months. These sessions included exercise coaching and supervised exercise. Patients could choose their preferred aerobic exercise and most picked brisk walking.

The consultants gave each patient an “exercise prescription” to hit a specific amount of exercise. The target was an additional 10 metabolic equivalent (MET)–hours of aerobic activity per week — about three to four brisk walks each lasting 45-60 minutes. After 6 months, patients met with their consultants once a month, with additional sessions available for extra support if needed.

Structured exercise led to “substantial and sustained” increases in the amount of exercise participants did, as well as physiologic measures of their fitness, with “highly relevant” improvements in VO₂ max, 6-minute walk test, and patient-reported physical function, underscoring that participants were not only exercising more but also getting fitter, Booth said.

Exercise was associated with a clinically meaningful and statistically significant 28% reduction in the risk for recurrent or new cancer (hazard ratio [HR], 0.72; P = .017), with a 5-year disease free survival rate of 80% in the exercise group and 74% in the control group.

In other words, “for every 16 patients that went on the exercise program, exercise prevented 1 person from recurrent or new cancer” at 5 years, Booth reported.

Overall survival results were “even more impressive,” he said.

At 8 years, 90% of patients in the exercise program were alive vs 83% of those in the control group, which translated to a 37% lower risk for death (HR, 0.63; P = .022).

“For every 14 patients who went on the exercise program, exercise prevented 1 person from dying” at the 8-year mark, Booth noted.

“Notably, this difference in survival was not driven by difference in cardiovascular deaths but by a reduction in the risk of death from colon cancer,” he said.

Besides a slight uptick in musculoskeletal aches, no major safety signals emerged in the exercise group.

It’s important to note that the survival benefit associated with exercise came after patients had received surgery followed by chemotherapy — in other words, exercise did not replace established cancer treatments. It’s also unclear whether initiating an exercise intervention earlier in the treatment trajectory — before surgery or during chemotherapy, instead of after chemotherapy — could further improve cancer outcomes, the authors noted.

Still, “exercise as an intervention is a no brainer and should be implemented broadly,” said ASCO expert Pamela Kunz, MD, with Yale School of Medicine, New Haven, Connecticut.

Marco Gerlinger, MD, with Barts Cancer Institute, London, England, agreed.

“Oncologists can now make a very clear evidence-based recommendation for patients who just completed their chemotherapy for bowel cancer and are fit enough for such an exercise program,” Gerlinger said in a statement from the nonprofit UK Science Media Centre.

Booth noted that knowledge alone will not be sufficient to allow most patients to change their lifestyle and realize the health benefits.

“The policy implementation piece of this is really key, and we need health systems, hospitals, and payers to invest in these behavior support programs so that patients have access to a physical activity consultant and can realize the health benefits,” he said.

“This intervention is empowering and achievable for patients and with much, much lower cost than many of our therapies. It is also sustainable for health systems,” he concluded.

Diet and Survival

Diet can also affect outcomes in patients with colon cancer.

In the same session describing the CHALLENGE results, Sara Char, MD, with Dana-Farber Cancer Institute in Boston, reported findings showing that consuming a diet high in proinflammatory foods was associated with worse overall survival in patients with stage III colon cancer. A proinflammatory diet includes red and processed meats, sugary drinks, and refined grains, while an anti-inflammatory diet focuses on fruits, vegetables, whole grains, fish, and olive oil.

Chronic systemic inflammation has been implicated in both colon cancer development and in its progression, and elevated levels of inflammatory markers in the blood have previously been associated with worse survival outcomes in patients with stage III colon cancer.

Char and colleagues analyzed dietary patterns of a subset of 1625 patients (mean age, 61 years) with resected stage III colon cancer enrolled in the phase 3 CALGB/SWOG 80702 (Alliance) clinical trial, which compared 3 months of adjuvant chemotherapy with 6 months of adjuvant chemotherapy, with or without the anti-inflammatory medication celecoxib.

As part of the trial, participants reported their diet and exercise habits at various timepoints. Their diets were scored using the validated empirical dietary inflammatory pattern (EDIP) tool, which is a weighted sum of 18 food groups — nine proinflammatory and nine anti-inflammatory. A high EDIP score marks a proinflammatory diet, and a low EDIP score indicates a less inflammatory diet.

During median follow-up of nearly 4 years, researchers noted a trend toward worse disease-free survival in patients with high proinflammatory diets (HR, 1.46), but this association was not significant in the multivariable adjusted model (HR, 1.36; P = .22), Char reported.

However, higher intake of proinflammatory foods was associated with significantly worse overall survival.

Patients who consumed the most proinflammatory foods (top 20%) had an 87% higher risk for death compared with those who consumed the least (bottom 20%; HR, 1.87). The median overall survival in the highest quintile was 7.7 years and was not reached in the lowest quintile.

Combine Exercise and Diet for Best Results

To examine the joint effect of physical activity and diet on overall survival, patients were divided into higher and lower levels of physical activity using a cut-off of 9 MET hours per week, which roughly correlates to 30 minutes of vigorous walking five days a week with a little bit of light yoga, Char explained.

In this analysis, patients with less proinflammatory diets and higher physical activity levels had the best overall survival outcomes, with a 63% lower risk for death compared with peers who consumed more pro-inflammatory diets and exercised less (HR, 0.37; P < .0001).

Daily celecoxib use and low-dose aspirin use (< 100 mg/d) did not affect the association between inflammatory diet and survival.

Char cautioned, that while the EDIP tool is useful to measure the inflammatory potential of a diet, “this is not a dietary recommendation, and we need further studies to be able to tailor our findings into dietary recommendations that can be provided to patients at the bedside.”

Gralow said this “early but promising observational study suggests a powerful synergy: Patients with stage III colon cancer who embraced anti-inflammatory foods and exercised regularly showed the best overall survival compared to those with inflammatory diets and limited exercise.”

The CHALLENGE trial was funded by the Canadian Cancer Society, the National Health and Medical Research Council, Cancer Research UK, and the University of Sydney Cancer Research Fund. Booth had no disclosures. The diet study was funded by the National Institutes of Health, Pfizer, and the Project P Fund. Char disclosed an advisory/consultant role with Goodpath. Kunz, Gralow and Campbell had no relevant disclosures.

A version of this article first appeared on Medscape.com.