Diet, Exercise, Common Drugs Lower Colorectal Cancer Risk

SAN FRANCISCO — Colorectal cancer risk reduction has been found to be highly associated with the use of several over-the-counter and prescription drugs, as well as with exercise and consumption of vegetables, in a large ongoing chemoprevention study in Israel.

Low-dose aspirin and statins, for example, each appeared to be protective in the case-control Molecular Epidemiology of Colorectal Cancer (MECC) study.

Combined, the protective benefit of the two drugs appeared to be even more powerful, reducing by 60% the relative risk of colorectal cancer in healthy adults, said Dr. Gad Rennert, director of the CHS National Israeli Cancer Control Center in Haifa.

Case-control studies do not produce strong evidence of an association, as would be seen in a randomized, controlled trial, Dr. Rennert noted at a symposium sponsored by the American Society of Clinical Oncology. But large studies such as MECC can examine multiple potential contributors to cancer risk—factors that are common to many people in the population. Fairly good evidence of an association can be seen if there are sharp differences in factors such as lifestyle or prescribed drugs between controls and people diagnosed with cancer.

In the MECC study, there was a lower relative risk of colorectal cancer in people taking aspirin and other nonsteroidal anti-inflammatory drugs, statins, allopurinol, and thyroxine, compared with people who were not using such agents. Those interventions were associated with even greater reductions in relative risk in a high-risk group: carriers of the APC 11307K genetic mutation, which is linked to a twofold elevation in risk of colorectal cancer in Ashkenazi Jews. (See box.)

“We see strong associations with very narrow confidence intervals—pretty much the dream of an epidemiologist,” Dr. Rennert said. The largest risk reductions were seen among subjects who participated in sports, ate five or more vegetables a day, and took either a statin or an aspirin or NSAID daily. These subjects had a relative risk of colorectal cancer of 0.22—a reduction of nearly 80%, compared with people with none of these protective factors. In the high-risk group, the protective factors combined to confer an 84% reduction in risk.

Referring to colorectal cancer as “a highly preventable disease,” Dr. Rennert said the MECC findings might ultimately point to preventive strategies for healthy people and, especially, those at high risk for the disease. The MECC study is a collaboration between Dr. Stephen B. Gruber of the University of Michigan, Ann Arbor, and Dr. Rennert in Israel. The research is funded by the National Institutes of Health.

More than 6,000 subjects have been enrolled, with one control for each patient newly diagnosed with colorectal cancer. The study draws on clinical and pharmacy records, pathology reports, and biopsy studies, as well as thorough interviews covering lifestyle and nutrition issues.

Applying the findings to preventive efforts becomes tricky, since any intervention must be weighed against possible harm. “Side effects are extremely important when you're talking about healthy people,” he noted. In people with a high risk for colorectal cancer because of a personal or family history or genetic profile, the balance may tip more in favor of preventive intervention.

There is little hope of ever studying the preventive benefit of low-dose aspirin or statins in a randomized, placebo-controlled trial, Dr. Rennert said, because the drugs are so commonly used that it would be hard to enroll an unbiased sample and ensure that results were not contaminated.

But the “very strong evidence” in the MECC case-control study suggests that these agents, when used for other indications by a wide variety of people, may reduce colorectal cancer rates in the future.

“Time will say whether this is the case or not,” he said at the meeting, which was also sponsored by the American Gastroenterological Association, the American Society for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology.

Low-dose aspirin and statins each appeared to be protective in the case-control study. DR. RENNERT

SAN FRANCISCO — Colorectal cancer risk reduction has been found to be highly associated with the use of several over-the-counter and prescription drugs, as well as with exercise and consumption of vegetables, in a large ongoing chemoprevention study in Israel.

Low-dose aspirin and statins, for example, each appeared to be protective in the case-control Molecular Epidemiology of Colorectal Cancer (MECC) study.

Combined, the protective benefit of the two drugs appeared to be even more powerful, reducing by 60% the relative risk of colorectal cancer in healthy adults, said Dr. Gad Rennert, director of the CHS National Israeli Cancer Control Center in Haifa.

Case-control studies do not produce strong evidence of an association, as would be seen in a randomized, controlled trial, Dr. Rennert noted at a symposium sponsored by the American Society of Clinical Oncology. But large studies such as MECC can examine multiple potential contributors to cancer risk—factors that are common to many people in the population. Fairly good evidence of an association can be seen if there are sharp differences in factors such as lifestyle or prescribed drugs between controls and people diagnosed with cancer.

In the MECC study, there was a lower relative risk of colorectal cancer in people taking aspirin and other nonsteroidal anti-inflammatory drugs, statins, allopurinol, and thyroxine, compared with people who were not using such agents. Those interventions were associated with even greater reductions in relative risk in a high-risk group: carriers of the APC 11307K genetic mutation, which is linked to a twofold elevation in risk of colorectal cancer in Ashkenazi Jews. (See box.)

“We see strong associations with very narrow confidence intervals—pretty much the dream of an epidemiologist,” Dr. Rennert said. The largest risk reductions were seen among subjects who participated in sports, ate five or more vegetables a day, and took either a statin or an aspirin or NSAID daily. These subjects had a relative risk of colorectal cancer of 0.22—a reduction of nearly 80%, compared with people with none of these protective factors. In the high-risk group, the protective factors combined to confer an 84% reduction in risk.

Referring to colorectal cancer as “a highly preventable disease,” Dr. Rennert said the MECC findings might ultimately point to preventive strategies for healthy people and, especially, those at high risk for the disease. The MECC study is a collaboration between Dr. Stephen B. Gruber of the University of Michigan, Ann Arbor, and Dr. Rennert in Israel. The research is funded by the National Institutes of Health.

More than 6,000 subjects have been enrolled, with one control for each patient newly diagnosed with colorectal cancer. The study draws on clinical and pharmacy records, pathology reports, and biopsy studies, as well as thorough interviews covering lifestyle and nutrition issues.

Applying the findings to preventive efforts becomes tricky, since any intervention must be weighed against possible harm. “Side effects are extremely important when you're talking about healthy people,” he noted. In people with a high risk for colorectal cancer because of a personal or family history or genetic profile, the balance may tip more in favor of preventive intervention.

There is little hope of ever studying the preventive benefit of low-dose aspirin or statins in a randomized, placebo-controlled trial, Dr. Rennert said, because the drugs are so commonly used that it would be hard to enroll an unbiased sample and ensure that results were not contaminated.

But the “very strong evidence” in the MECC case-control study suggests that these agents, when used for other indications by a wide variety of people, may reduce colorectal cancer rates in the future.

“Time will say whether this is the case or not,” he said at the meeting, which was also sponsored by the American Gastroenterological Association, the American Society for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology.

Low-dose aspirin and statins each appeared to be protective in the case-control study. DR. RENNERT

SAN FRANCISCO — Colorectal cancer risk reduction has been found to be highly associated with the use of several over-the-counter and prescription drugs, as well as with exercise and consumption of vegetables, in a large ongoing chemoprevention study in Israel.

Low-dose aspirin and statins, for example, each appeared to be protective in the case-control Molecular Epidemiology of Colorectal Cancer (MECC) study.

Combined, the protective benefit of the two drugs appeared to be even more powerful, reducing by 60% the relative risk of colorectal cancer in healthy adults, said Dr. Gad Rennert, director of the CHS National Israeli Cancer Control Center in Haifa.

Case-control studies do not produce strong evidence of an association, as would be seen in a randomized, controlled trial, Dr. Rennert noted at a symposium sponsored by the American Society of Clinical Oncology. But large studies such as MECC can examine multiple potential contributors to cancer risk—factors that are common to many people in the population. Fairly good evidence of an association can be seen if there are sharp differences in factors such as lifestyle or prescribed drugs between controls and people diagnosed with cancer.

In the MECC study, there was a lower relative risk of colorectal cancer in people taking aspirin and other nonsteroidal anti-inflammatory drugs, statins, allopurinol, and thyroxine, compared with people who were not using such agents. Those interventions were associated with even greater reductions in relative risk in a high-risk group: carriers of the APC 11307K genetic mutation, which is linked to a twofold elevation in risk of colorectal cancer in Ashkenazi Jews. (See box.)

“We see strong associations with very narrow confidence intervals—pretty much the dream of an epidemiologist,” Dr. Rennert said. The largest risk reductions were seen among subjects who participated in sports, ate five or more vegetables a day, and took either a statin or an aspirin or NSAID daily. These subjects had a relative risk of colorectal cancer of 0.22—a reduction of nearly 80%, compared with people with none of these protective factors. In the high-risk group, the protective factors combined to confer an 84% reduction in risk.

Referring to colorectal cancer as “a highly preventable disease,” Dr. Rennert said the MECC findings might ultimately point to preventive strategies for healthy people and, especially, those at high risk for the disease. The MECC study is a collaboration between Dr. Stephen B. Gruber of the University of Michigan, Ann Arbor, and Dr. Rennert in Israel. The research is funded by the National Institutes of Health.

More than 6,000 subjects have been enrolled, with one control for each patient newly diagnosed with colorectal cancer. The study draws on clinical and pharmacy records, pathology reports, and biopsy studies, as well as thorough interviews covering lifestyle and nutrition issues.

Applying the findings to preventive efforts becomes tricky, since any intervention must be weighed against possible harm. “Side effects are extremely important when you're talking about healthy people,” he noted. In people with a high risk for colorectal cancer because of a personal or family history or genetic profile, the balance may tip more in favor of preventive intervention.

There is little hope of ever studying the preventive benefit of low-dose aspirin or statins in a randomized, placebo-controlled trial, Dr. Rennert said, because the drugs are so commonly used that it would be hard to enroll an unbiased sample and ensure that results were not contaminated.

But the “very strong evidence” in the MECC case-control study suggests that these agents, when used for other indications by a wide variety of people, may reduce colorectal cancer rates in the future.

“Time will say whether this is the case or not,” he said at the meeting, which was also sponsored by the American Gastroenterological Association, the American Society for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology.

Low-dose aspirin and statins each appeared to be protective in the case-control study. DR. RENNERT