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|Title:||Quantifying Mediating Effects of Endogenous Estrogen and Insulin in the Relation between Obesity, Alcohol Consumption, and Breast Cancer||Authors:||Hvidtfeldt, Ulla A.
Gunter, Marc J.
Farhat, Ghada N.
|Affiliations:||Department of Public Health||Issue Date:||2012||Part of:||Cancer epidemiology biomarkers and prevention||Volume:||21||Issue:||7||Abstract:||
Background: Increased exposure to endogenous estrogen and/or insulin may partly explain the relationship of obesity, physical inactivity, and alcohol consumption and postmenopausal breast cancer. However, these potential mediating effects have not been formally quantified in a survival analysis setting. Methods: We combined data from two case–cohort studies based in the Women's Health Initiative-Observational Study with serum estradiol levels, one of which also had insulin levels. A total of 1,601 women (601 cases) aged 50 to 79 years who were not using hormone therapy at enrollment were included. Mediating effects were estimated by applying a new method based on the additive hazard model. Results: A five-unit increase in body mass index (BMI) was associated with 50.0 [95% confidence interval (CI), 23.2–76.6] extra cases per 100,000 women at-risk per year. Of these, 23.8% (95% CI, 2.9–68.4) could be attributed to estradiol and 65.8% (95% CI, 13.6–273.3) through insulin pathways. The mediating effect of estradiol was greater (48.8%; 95% CI, 18.8–161.1) for BMI when restricted to estrogen receptor positive (ER+) cases. Consuming 7+ drinks/wk compared with abstinence was associated with 164.9 (95% CI, 45.8–284.9) breast cancer cases per 100,000, but no significant contribution from estradiol was found. The effect of alcohol on breast cancer was restricted to ER+ breast cancers. Conclusions: The relation of BMI with breast cancer was partly mediated through estradiol and, to a greater extent, through insulin.
|URI:||https://scholarhub.balamand.edu.lb/handle/uob/2463||Open URL:||Link to full text||Type:||Journal Article|
|Appears in Collections:||Department of Public Health|
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