Geography Linked to IBD Incidence in Women

Geographic location could be associated with incidence of inflammatory bowel disease, based on a new study showing that women living in southern portions of the United States had a lower incidence than did those living in northern regions of the country.

Previous studies conducted in Europe have suggested that living in southern latitudes may be linked to lower risk for inflammatory bowel disease.

The researchers in the current study looked at where the women had lived at age 30 years, and found that those living in southern latitudes had a significantly lower multivariate-adjusted hazard ratio (HR) for ulcerative colitis (UC), at 0.62, and for Crohn’s disease (CD), at 0.48, compared with women living in northern areas (P for trend less than .01).

"The lower risk of UC associated with decreasing latitude appeared stronger according to residence at older ages."

"These results were consistent even after accounting for differences in self-reported ancestry and smoking, suggesting that other environmental or lifestyle factors correlated with geographical variation may mediate these associations," wrote Dr. Hamed Khalili and his coinvestigators. Dr. Khalili is a gastroenterologist at Massachusetts General Hospital in Boston.

The findings, from an analysis of data from more than 500 women involved in either the Nurses’ Health Study I (NHS I) or the Nurses’ Health Study II (NHS II), were published Jan. 11 in the journal Gut (Gut 2012 Jan. 11 [doi:10.1136/gutjnl-2011-301574]).

The NHS I is a prospective cohort that began in 1976 with 121,700 U.S. female registered nurses aged 30-55 years who completed a mailed health questionnaire. Follow-up questionnaires have been mailed every 2 years to update health information.

In 1989, a parallel cohort, the NHS II, enrolled 116,686 U.S. female nurses aged 25-42 years. These women have been followed with similar biennial questionnaires. Participants in both cohorts reported their state of residence at birth, age 15 years, and age 30 years.

In NHS I, participants were specifically asked about diagnoses of UC since 1982 and CD since 1992. In NHS II, participants were asked about diagnoses of both UC and CD since 1993. In both cohorts, when a diagnosis was reported on any biennial questionnaire, related medical records were requested and reviewed by two gastroenterologists blinded to exposure information.

The researchers identified 257 incident cases of CD and 313 incident cases of UC through the end of follow-up, with diagnoses based on standardized criteria. The authors also noted that baseline characteristics of participants with complete medical records were similar to those of participants for whom they were unable to obtain sufficient records.

To analyze the geographic data, the investigators divided the continental United States into northern, middle, and southern tiers of latitude. The northern tier states are Connecticut, Maine, Massachusetts, New Hampshire, New York, Rhode Island, Vermont, Michigan, Minnesota, Wisconsin, Idaho, Montana, Nebraska, North Dakota, South Dakota, Wyoming, Oregon, Washington, and Alaska. The southern tier consists of Florida, Georgia, North Carolina, South Carolina, Alabama, Arkansas, Louisiana, Mississippi, Tennessee, Arizona, New Mexico, Oklahoma, Texas, southern California, Hawaii, and Puerto Rico. The middle tier consists of Delaware, the District of Columbia, Maryland, New Jersey, Pennsylvania, Virginia, West Virginia, Illinois, Indiana, Iowa, Kentucky, Missouri, Ohio, Colorado, Kansas, Nevada, Utah, and northern California.

"The lower risk of UC associated with decreasing latitude appeared stronger according to residence at older ages," the researchers noted. For example, the multivariate-adjusted HRs for UC were 0.67 for women who resided in southern latitudes at age 15 and 0.62 for women who resided in southern latitudes at age 30. "This effect was consistent, although somewhat attenuated according to latitude of residence at birth or age 15."

For UC, data on residence at birth showed that the multivariate hazard ratio was 1.00 for women born at middle latitudes and 0.69 women born at southern latitudes, compared with women born at northern latitudes.

"This association was not materially changed when we restricted the analysis to women who resided in the same latitude at birth, age 15, and age 30," they wrote. Compared with women who had lived consistently in northern latitudes, the multivariate-adjusted HR was 0.63 for women who lived consistently in southern latitudes.

Similar results were seen for women with CD. Compared with women who resided in northern latitudes at age 30, the multivariate-adjusted HRs were 0.84 for women who resided in middle latitudes at age 30 and 0.48 for women who resided in southern latitudes at age 30.

"Although statistical power was limited, these effect estimates were not materially altered when we restricted the analyses to women who resided in the same latitudes at birth, age 15, and age 30," the researchers observed. Thus, compared with women who resided consistently in northern latitudes, the multivariate-adjusted HR was 0.77 for women who resided consistently in middle latitudes and 0.65 for women who lived consistently in southern latitudes.

"In contrast with UC, there did not appear to be a significantly lower risk of CD according to latitude based only upon residence at birth or age 15."

The reason for this apparent association between latitude and inflammatory bowel disease incidence is not clear. However, "a leading explanation for this ‘north-south’ gradient in the risk of UC and CD may be differences in exposure to sunlight or UVB radiation, which is generally greater in southern latitudes. UV radiation is the greatest environmental determinant of plasma vitamin D and there is substantial experimental data supporting a role for vitamin D in the innate immunity and regulation of inflammatory response," the researchers noted.

Funding was provided by the National Institutes of Health and the Broad Medical Research Program of the Broad Foundation. One researcher reported previously being a consultant for Bayer Healthcare and Millennium Pharmaceuticals. No other disclosures were reported.

Geographic location could be associated with incidence of inflammatory bowel disease, based on a new study showing that women living in southern portions of the United States had a lower incidence than did those living in northern regions of the country.

Previous studies conducted in Europe have suggested that living in southern latitudes may be linked to lower risk for inflammatory bowel disease.

The researchers in the current study looked at where the women had lived at age 30 years, and found that those living in southern latitudes had a significantly lower multivariate-adjusted hazard ratio (HR) for ulcerative colitis (UC), at 0.62, and for Crohn’s disease (CD), at 0.48, compared with women living in northern areas (P for trend less than .01).

"The lower risk of UC associated with decreasing latitude appeared stronger according to residence at older ages."

"These results were consistent even after accounting for differences in self-reported ancestry and smoking, suggesting that other environmental or lifestyle factors correlated with geographical variation may mediate these associations," wrote Dr. Hamed Khalili and his coinvestigators. Dr. Khalili is a gastroenterologist at Massachusetts General Hospital in Boston.

The findings, from an analysis of data from more than 500 women involved in either the Nurses’ Health Study I (NHS I) or the Nurses’ Health Study II (NHS II), were published Jan. 11 in the journal Gut (Gut 2012 Jan. 11 [doi:10.1136/gutjnl-2011-301574]).

The NHS I is a prospective cohort that began in 1976 with 121,700 U.S. female registered nurses aged 30-55 years who completed a mailed health questionnaire. Follow-up questionnaires have been mailed every 2 years to update health information.

In 1989, a parallel cohort, the NHS II, enrolled 116,686 U.S. female nurses aged 25-42 years. These women have been followed with similar biennial questionnaires. Participants in both cohorts reported their state of residence at birth, age 15 years, and age 30 years.

In NHS I, participants were specifically asked about diagnoses of UC since 1982 and CD since 1992. In NHS II, participants were asked about diagnoses of both UC and CD since 1993. In both cohorts, when a diagnosis was reported on any biennial questionnaire, related medical records were requested and reviewed by two gastroenterologists blinded to exposure information.

The researchers identified 257 incident cases of CD and 313 incident cases of UC through the end of follow-up, with diagnoses based on standardized criteria. The authors also noted that baseline characteristics of participants with complete medical records were similar to those of participants for whom they were unable to obtain sufficient records.

To analyze the geographic data, the investigators divided the continental United States into northern, middle, and southern tiers of latitude. The northern tier states are Connecticut, Maine, Massachusetts, New Hampshire, New York, Rhode Island, Vermont, Michigan, Minnesota, Wisconsin, Idaho, Montana, Nebraska, North Dakota, South Dakota, Wyoming, Oregon, Washington, and Alaska. The southern tier consists of Florida, Georgia, North Carolina, South Carolina, Alabama, Arkansas, Louisiana, Mississippi, Tennessee, Arizona, New Mexico, Oklahoma, Texas, southern California, Hawaii, and Puerto Rico. The middle tier consists of Delaware, the District of Columbia, Maryland, New Jersey, Pennsylvania, Virginia, West Virginia, Illinois, Indiana, Iowa, Kentucky, Missouri, Ohio, Colorado, Kansas, Nevada, Utah, and northern California.

"The lower risk of UC associated with decreasing latitude appeared stronger according to residence at older ages," the researchers noted. For example, the multivariate-adjusted HRs for UC were 0.67 for women who resided in southern latitudes at age 15 and 0.62 for women who resided in southern latitudes at age 30. "This effect was consistent, although somewhat attenuated according to latitude of residence at birth or age 15."

For UC, data on residence at birth showed that the multivariate hazard ratio was 1.00 for women born at middle latitudes and 0.69 women born at southern latitudes, compared with women born at northern latitudes.

"This association was not materially changed when we restricted the analysis to women who resided in the same latitude at birth, age 15, and age 30," they wrote. Compared with women who had lived consistently in northern latitudes, the multivariate-adjusted HR was 0.63 for women who lived consistently in southern latitudes.

Similar results were seen for women with CD. Compared with women who resided in northern latitudes at age 30, the multivariate-adjusted HRs were 0.84 for women who resided in middle latitudes at age 30 and 0.48 for women who resided in southern latitudes at age 30.

"Although statistical power was limited, these effect estimates were not materially altered when we restricted the analyses to women who resided in the same latitudes at birth, age 15, and age 30," the researchers observed. Thus, compared with women who resided consistently in northern latitudes, the multivariate-adjusted HR was 0.77 for women who resided consistently in middle latitudes and 0.65 for women who lived consistently in southern latitudes.

"In contrast with UC, there did not appear to be a significantly lower risk of CD according to latitude based only upon residence at birth or age 15."

The reason for this apparent association between latitude and inflammatory bowel disease incidence is not clear. However, "a leading explanation for this ‘north-south’ gradient in the risk of UC and CD may be differences in exposure to sunlight or UVB radiation, which is generally greater in southern latitudes. UV radiation is the greatest environmental determinant of plasma vitamin D and there is substantial experimental data supporting a role for vitamin D in the innate immunity and regulation of inflammatory response," the researchers noted.

Funding was provided by the National Institutes of Health and the Broad Medical Research Program of the Broad Foundation. One researcher reported previously being a consultant for Bayer Healthcare and Millennium Pharmaceuticals. No other disclosures were reported.

Geographic location could be associated with incidence of inflammatory bowel disease, based on a new study showing that women living in southern portions of the United States had a lower incidence than did those living in northern regions of the country.

Previous studies conducted in Europe have suggested that living in southern latitudes may be linked to lower risk for inflammatory bowel disease.

The researchers in the current study looked at where the women had lived at age 30 years, and found that those living in southern latitudes had a significantly lower multivariate-adjusted hazard ratio (HR) for ulcerative colitis (UC), at 0.62, and for Crohn’s disease (CD), at 0.48, compared with women living in northern areas (P for trend less than .01).

"The lower risk of UC associated with decreasing latitude appeared stronger according to residence at older ages."

"These results were consistent even after accounting for differences in self-reported ancestry and smoking, suggesting that other environmental or lifestyle factors correlated with geographical variation may mediate these associations," wrote Dr. Hamed Khalili and his coinvestigators. Dr. Khalili is a gastroenterologist at Massachusetts General Hospital in Boston.

The findings, from an analysis of data from more than 500 women involved in either the Nurses’ Health Study I (NHS I) or the Nurses’ Health Study II (NHS II), were published Jan. 11 in the journal Gut (Gut 2012 Jan. 11 [doi:10.1136/gutjnl-2011-301574]).

The NHS I is a prospective cohort that began in 1976 with 121,700 U.S. female registered nurses aged 30-55 years who completed a mailed health questionnaire. Follow-up questionnaires have been mailed every 2 years to update health information.

In 1989, a parallel cohort, the NHS II, enrolled 116,686 U.S. female nurses aged 25-42 years. These women have been followed with similar biennial questionnaires. Participants in both cohorts reported their state of residence at birth, age 15 years, and age 30 years.

In NHS I, participants were specifically asked about diagnoses of UC since 1982 and CD since 1992. In NHS II, participants were asked about diagnoses of both UC and CD since 1993. In both cohorts, when a diagnosis was reported on any biennial questionnaire, related medical records were requested and reviewed by two gastroenterologists blinded to exposure information.

The researchers identified 257 incident cases of CD and 313 incident cases of UC through the end of follow-up, with diagnoses based on standardized criteria. The authors also noted that baseline characteristics of participants with complete medical records were similar to those of participants for whom they were unable to obtain sufficient records.

To analyze the geographic data, the investigators divided the continental United States into northern, middle, and southern tiers of latitude. The northern tier states are Connecticut, Maine, Massachusetts, New Hampshire, New York, Rhode Island, Vermont, Michigan, Minnesota, Wisconsin, Idaho, Montana, Nebraska, North Dakota, South Dakota, Wyoming, Oregon, Washington, and Alaska. The southern tier consists of Florida, Georgia, North Carolina, South Carolina, Alabama, Arkansas, Louisiana, Mississippi, Tennessee, Arizona, New Mexico, Oklahoma, Texas, southern California, Hawaii, and Puerto Rico. The middle tier consists of Delaware, the District of Columbia, Maryland, New Jersey, Pennsylvania, Virginia, West Virginia, Illinois, Indiana, Iowa, Kentucky, Missouri, Ohio, Colorado, Kansas, Nevada, Utah, and northern California.

"The lower risk of UC associated with decreasing latitude appeared stronger according to residence at older ages," the researchers noted. For example, the multivariate-adjusted HRs for UC were 0.67 for women who resided in southern latitudes at age 15 and 0.62 for women who resided in southern latitudes at age 30. "This effect was consistent, although somewhat attenuated according to latitude of residence at birth or age 15."

For UC, data on residence at birth showed that the multivariate hazard ratio was 1.00 for women born at middle latitudes and 0.69 women born at southern latitudes, compared with women born at northern latitudes.

"This association was not materially changed when we restricted the analysis to women who resided in the same latitude at birth, age 15, and age 30," they wrote. Compared with women who had lived consistently in northern latitudes, the multivariate-adjusted HR was 0.63 for women who lived consistently in southern latitudes.

Similar results were seen for women with CD. Compared with women who resided in northern latitudes at age 30, the multivariate-adjusted HRs were 0.84 for women who resided in middle latitudes at age 30 and 0.48 for women who resided in southern latitudes at age 30.

"Although statistical power was limited, these effect estimates were not materially altered when we restricted the analyses to women who resided in the same latitudes at birth, age 15, and age 30," the researchers observed. Thus, compared with women who resided consistently in northern latitudes, the multivariate-adjusted HR was 0.77 for women who resided consistently in middle latitudes and 0.65 for women who lived consistently in southern latitudes.

"In contrast with UC, there did not appear to be a significantly lower risk of CD according to latitude based only upon residence at birth or age 15."

The reason for this apparent association between latitude and inflammatory bowel disease incidence is not clear. However, "a leading explanation for this ‘north-south’ gradient in the risk of UC and CD may be differences in exposure to sunlight or UVB radiation, which is generally greater in southern latitudes. UV radiation is the greatest environmental determinant of plasma vitamin D and there is substantial experimental data supporting a role for vitamin D in the innate immunity and regulation of inflammatory response," the researchers noted.

Funding was provided by the National Institutes of Health and the Broad Medical Research Program of the Broad Foundation. One researcher reported previously being a consultant for Bayer Healthcare and Millennium Pharmaceuticals. No other disclosures were reported.