Abstract LB-338: A prospective evaluation of circulating sex hormones in relation to colorectal cancer risk in men and women
Authors: Lin Jennifer-Hsiang-Ling , Zhang Shumin , Rexrode Kathy , Manson JoAnn , Andrew Chan , Wu Kana , Tworoger Shelley , Hankinson Susan , Fuchs Charles , Gaziano Michael , Buring Julie , Giovannucci Edward 
Published: August 2012

Abstract
Background: Observational studies and randomized trials have supported a potential role of sex hormones in colorectal cancer development in both men and women. However, data on the relationship between endogenous sex hormone levels and colorectal cancer are very limited. Methods: We prospectively evaluated plasma levels of estrone, estradiol, and testosterone in relation to colorectal cancer risk in men and postmenopausal women not using hormone therapy from four large female and male study cohorts including the Nurses’ Health Study, Women's Health Study, Health Professional Follow-Up Study, and Physicians’ Health Study II. A total of 293 female and 438 male cases along with 437 female and 719 male controls were included in the present analysis. Unconditional logistic regression controlling for matching, risk factors, and plasma c-peptide was used to estimate relative risks (RRs) and 95% confidence intervals (CIs). All statistical tests were two sided. Results: Total testosterone, sex hormone binding globulin (SHBG), and the ratio of estradiol over testosterone were associated with colorectal cancer in men after adjustment for all confounding factors including body mass index (BMI) and c-peptide levels; the RRs (95% CI) in the highest relative to the lowest quartile were 0.62 (0.40-0.96) for testosterone, 0.65 (0.42-0.99) for SHBG, and 2.63 (1.58-4.36) for the ratio (p-values for trend ≤0.02). In addition, no effect modification by BMI in men was found on the association between sex steroids and colorectal cancer (p-values for interaction ≥0.46). In women, a higher ratio of estradiol to testosterone, reflecting higher aromatase activity and likely increased estradiol production, was associated with lower colorectal cancer risk after adjustment for all factors (RR=0.43, 95% CI=0.22-0.84, p-value for trend=0.03). Specifically, the inverse association between the ratio and colorectal cancer risk was seen only among normal weight women (p-value for interaction=0.07); the multivariate RRs in the higher quartile groups were 0.26-0.72 (p-value for tend=0.03). Conversely, there was no association between the ratio and colorectal cancer in overweight and obese women (RRs=1.15-1.2, p-value for trend=0.89). Stratifying analysis by BMI for other sex steroids did not significantly change the overall association (p-values for interaction ≥0.25). Conclusion: Our data offers the first observational evidence supporting an inverse association of circulating testosterone and SHBG with colorectal cancer in men. Conversely, normal weight women with a higher ratio of estradiol over testosterone may be at a lower risk for colorectal cancer. Validation of our results in other studies will help elucidate the effects attributable to sex steroids on colorectal cancer and refine risk profiles of colorectal cancer development in both men and women.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-338. doi:1538-7445.AM2012-LB-338