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||Estrogen Metabolites Are Not Associated With Colorectal Cancer Risk In Postmenopausal Women.
||Falk RT, Dallal CM, Lacey JV Jr, Bauer DC, Buist DS, Cauley JA, Hue TF, LaCroix AZ, Tice JA, Pfeiffer RM, Xu X, Veenstra TD, Brinton LA
||Cancer Epidemiol Biomarkers Prev
||2015 Jun 23
||BB, EBP, HREB
||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 (CRC) 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) enrolled in B~FIT (Breast and Bone Follow-up to the Fracture Intervention Trial (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 CRC 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 v Q1=1.15, 95% CI=0.69-1.93, ptrend=0.54), estradiol (HRQ4 v Q1= 0.98, 95% CI=0.58-1.64, ptrend>0.99) or total EM (the sum of all EM; HRQ4 v 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. CONCLUSIONS: Circulating estrogens and their metabolites were generally unrelated to CRC risk in postmenopausal women. IMPACT: Additional studies are needed to understand how exogenous estrogen may prevent CRC.