Estrogen metabolites are not associated with colorectal cancer risk in postmenopausal women

Abstract

Background: A potential protective role for estrogen in colon carcinogenesis has been suggested based on exogenous hormone use, but it is unclear from previous studies whether endogenous estrogens are related to colorectal cancer risk. These few prior studies focused on parent estrogens; none evaluated effects of estrogen metabolism in postmenopausal women. Methods: We followed 15,595 women (ages 55-80 years) enrolled in the Breast and Bone Follow-up to the Fracture Intervention Trial (B~FIT) who donated blood between 1992 and 1993 for cancer through December 2004. A panel of 15 estrogen metabolites (EM), including estradiol and estrone, were measured in serum from 187 colorectal cancer cases and a subcohort of 501 women not using exogenous hormones at blood draw. We examined EM individually, grouped by pathway (hydroxylation at the C-2, C-4, or C-16 position) and by ratios of the groupings using Cox proportional hazards regression models. Results: No significant associations were seen for estrone (HRQ4 vs. Q1 = 1.15; 95% CI, 0.69-1.93; Ptrend = 0.54), estradiol (HRQ4 vs. Q1=0.98; 95% CI, 0.58-1.64; Ptrend > 0.99), or total EM (the sum of all EM;HRQ4 vs. Q1=1.35;95%CI, 0.81-2.24; Ptrend= 0.33). Most metabolites in the 2-, 4-, or 16-pathway were unrelated to risk, although a borderline trend in risk was associated with high levels of 17-epiestriol. Conclusion: Circulating estrogens and their metabolites were generally unrelated to colorectal cancer risk in postmenopausal women. Impact: Additional studies are needed to understand how exogenous estrogen may prevent colorectal cancer.