Background: Adiponectin is an insulin-sensitizing hormone secreted by adipocytes. Levels of adiponectin are inversely associated with adiposity and insulin resistance. Because both adiposity and insulin resistance have been associated with risk of colorectal cancer, we hypothesized that adiponectin is associated with colorectal carcinogenesis.

Methods: We evaluated the association between adiponectin and colorectal cancer among 18 225 men in the Health Professionals Follow-up Study who provided blood samples in 1994. Between blood collection and January 31, 2002, 179 incident colorectal cancer cases occurred. Each case patient was matched to two control subjects on year of birth and date of blood draw. Information on lifestyle factors and diet was collected using biennial questionnaires and food frequency questionnaires. Logistic regression models were used to estimate relative risks (RRs) and confidence intervals (CIs). All statistical tests were two-sided.

Results: We observed a statistically significant inverse association between plasma adiponectin levels and risk of colorectal cancer (for the highest quintile [Q5] versus the lowest quintile [Q1], RR = 0.42, 95% CI = 0.23 to 0.78; P(trend) = .01). The association was only slightly attenuated after adjustment for body mass index (Q5 versus Q1, RR = 0.48, 95% CI = 0.25 to 0.90; P(trend) = .04) or for body mass index and other major risk factors for colorectal cancer (family history, physical activity, multivitamin use, smoking, alcohol, aspirin use, history of endoscopy, dietary calcium, folate, vitamin E, and vitamin D; Q5 versus Q1, multivariable RR = 0.50, 95% CI = 0.26 to 0.97; P(trend) = .08). Relative risks were not linear in any of the analyses; the second quintile had a lower relative risk than the lowest quintile, but further decreases in risk were not evident with increasing levels of adiponectin.

Conclusions: In this prospective nested case-control study, men with low plasma adiponectin levels had a higher risk of colorectal cancer than men with higher levels. More prospective observational studies, particularly in women, and mechanistic studies are required to fully understand the relationship between adiponectin and carcinogenesis.