BACKGROUND: Higher body mass index (BMI) and circulating @entity172 levels each increase @entity0 risk, particularly @entity172 receptor-positive (ER(+)) @entity5 . Higher BMI also increases @entity172 production. METHODS: We estimated the proportion of the BMI-ER(+) @entity0 association mediated through @entity172 in a case-control study nested within the Prostate, Lung, Colorectal, and @entity43 Screening Trial. @entity1 included 143 @entity1 with invasive ER(+) @entity0 and 268 matched controls, all postmenopausal and never having used hormone therapy at baseline. We used liquid chromatography-tandem mass spectrometry to measure 15 @entity172 and @entity172 metabolites in baseline serum. We calculated BMI from self-reported height and weight at baseline. We estimated the mediating effect of unconjugated @entity53 on the BMI-ER(+) @entity0 association using Aalen additive hazards and Cox regression models. RESULTS: All @entity172 and @entity172 metabolites were statistically significantly correlated with BMI, with unconjugated @entity53 most strongly correlated [Pearson correlation (r) = 0.45]. Approximately 7% to 10% of the effect of overweight, 12% to 15% of the effect of @entity28 , and 19% to 20% of the effect of a 5 kg/m(2) BMI increase on ER(+) @entity0 risk was mediated through unconjugated @entity53 . The BMI- @entity0 association, once adjusted for unconjugated @entity53 , was not modified by further adjustment for two metabolic ratios statistically significantly associated with both @entity0 and BMI. CONCLUSION: Circulating unconjugated @entity53 levels partially mediate the BMI- @entity0 association, but other potentially important @entity172 mediators (e.g., bioavailable @entity53 ) were not evaluated. IMPACT: Further research is required to identify mechanisms underlying the BMI- @entity0 association. Cancer Epidemiol Biomarkers Prev; 25(1); 1-9.   2015 AACR.

Quantifying the Role of Circulating Unconjugated XXXX in Mediating the Body Mass Index-Breast Cancer Association.

@entity172 :: ('MESH:D004967', 'Chemical') :: ['estrogen', 'estrogens'] @entity1 :: ('9606', 'Species') :: ['women', 'Participants'] @entity43 :: ('MESH:D010051', 'Disease') :: ['Ovarian Cancer'] @entity0 :: ('MESH:D001943', 'Disease') :: ['postmenopausal breast cancer', 'breast cancer'] @entity28 :: ('MESH:D009765', 'Disease') :: ['obesity'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumors'] @entity53 :: ('MESH:D004958', 'Chemical') :: ['estradiol']
@entity53 :: (MESH:D004958,Chemical) :: ['Estradiol']
