Plasma Levels Of Pre-Diagnostic Sex Hormones And Mortality Among Patients With Colorectal Cancer - Results From Four Cohort Studies.

Abstract Background: Although increasing evidence suggests a role of sex hormones in colorectal cancer development, no previous studies, to our knowledge, have examined the influence of sex hormones on the outcome of patients with colorectal cancer. Methods: We conducted the first study to evaluate whether pre-diagnostic sex hormones including testosterone, estradiol, estrone, and sex hormone binding globulin(SHBG) were associated with mortality among 561 patients with pathologically confirmed colorectal adenocarcinoma (338 in men and 213 in women) diagnosed from 1990 to 2009 in four US cohorts: the Physicians' Health Study II(PHS II), the Health Professionals Follow-up Study(HPFS), the Nurses' Health Study(NHS), and the Women's Health Study(WHS). Participants were followed up until date of death, or end of the follow up [June 2010(PHS II), January 2012(HPFS), June 2009(NHS), or November 2011(WHS)], whichever occurred first. Cox proportional hazard regression models were used to calculate hazard ratios (HR) adjusted for other risk factors for cancer survival including age at diagnosis, grade of tumor differentiation, primary location of the tumor, status of tumor metastasis, as well as pre-diagnostic measures of body mass index and physical activity. Results: We identified 221 deaths(132 in men and 89 in women). Testosterone, estradiol, and SHBG were not associated with mortality in both male and female patients. However, there was an association of borderline significance between free (or bioavailable) testosterone and mortality among patients of both genders. Specifically, in men, higher levels of free testosterone were associated with a lower risk of overall mortality (top vs. bottom tertile HR=0.65, 95%CIs: 0.41-1.04, p-trend=0.07) and colorectal cancer-specific mortality (HR=0.61, 95%CIs: 0.31-1.19, p-trend=0.14). In contrast, there was a positive association in women between free testosterone and overall mortality (HR=1.66, 95%CIs: 0.90-3.06, p-trend=0.13, p-value for interaction by gender=0.02) and colorectal cancer-specific mortality (HR=1.92, 95%CIs: 0.93-3.98, p-trend=0.07, p-value for interaction by gender=0.02). Results remained essentially unchanged after further adjustment for plasma pre-diagnostic C-peptide levels. Moreover, higher estrone levels were associated with an elevated risk of overall mortality (HR=2.06, 95%CIs: 1.14-3.72, p-trend=0.02) and colorectal cancer-specific mortality (HR=2.73, 95%CIs: 1.25-5.93, p-trend=0.02) in women. Conclusion: Findings from our study suggest that higher pre-diagnostic free testosterone level may be associated with lower mortality for men but higher mortality in women in colorectal cancer patients. The observed positive association between estrone and mortality in women likely reflected the adverse effects of adiposity, which warrants further investigation. Citation Format: Xuehong Zhang, Edward L. Giovannucci, Andrew T. Chan, Kana Wu, Charles S. Fuchs, I-Min Lee, Julie E. Buring, J. Michael Gaziano, Howard D. Sesso, Jennifer H. Lin. Plasma levels of pre-diagnostic sex hormones and mortality among patients with colorectal cancer - Results from four cohort studies. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-19. doi:10.1158/1538-7445.AM2013-LB-19