Low Plasma Adiponectin Levels and Risk of Colorectal Cancer in Men: A Prospective Study

Esther K. Wei, Edward Giovannucci, Charles S. Fuchs, Walter C. Willett, Christos S. Mantzoros
2005 Journal of the National Cancer Institute  
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
more » ... s 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 confi dence intervals (CIs). All statistical tests were twosided. Results: We observed a statistically signifi cant 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 pro spective 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. [J Natl Cancer Inst 2005;97:1688 -94] Evidence is accumulating that obesity and hyperinsulinemia are involved in the etiology of colorectal cancer ( 1 ) . A sedentary lifestyle, high body fat level, and type 2 diabetes are all associated with insulin resistance, hyperinsulinemia, and colorectal cancer ( 2 -6 ) . Also, surrogate biologic measures of hyperinsulinemia, including high circulating levels of C-peptide and insulin-like growth factor -binding protein 1 (IGFBP-1), have been associated with risk of colorectal cancer ( 7 -10 ) . Adiponectin (Acrp30, AdipoQ, apM1, or GBP28), a protein hormone that is secreted exclusively by adipocytes, has potent insulin-sensitizing effects ( 11 -13 ) . Circulating levels of adiponectin are low in conditions characterized by insulin-resistant Affi liations of authors:
doi:10.1093/jnci/dji376 pmid:16288122 fatcat:wcukl2eklndw5dqn2omgr5axiu