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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Quantifying mediating effects of endogenous estrogen and insulin in the relation between obesity, alcohol consumption, and breast cancer
Cancer Epidemiology Biomarkers and Prevention, Volume 21, No. 7, Year 2012
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Description
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. Impact: The findings provide support for evaluation of interventions to lower insulin and estrogen levels in overweight and obese postmenopausal women to reduce breast cancer risk. ©2012 AACR.
Authors & Co-Authors
Hvidtfeldt, Ulla A.
Denmark, Copenhagen
Københavns Universitet
Gunter, Marc J.R.
United Kingdom, London
Imperial College London
Lange, Theis
Denmark, Copenhagen
Københavns Universitet
Chlebowski, Rowan T.
United States, Torrance
Harbor-ucla Medical Center
Lane, Dorothy S.
United States, Stony Brook
Stony Brook University
Farhat, Ghada N.
Lebanon, Al Koura
University of Balamand
Freiberg, Matthew S.
United States, Pittsburgh
University of Pittsburgh School of Medicine
Keiding, Niels
Denmark, Copenhagen
Københavns Universitet
Lee, Jennifer S.
United States, Davis
University of California, Davis
Prentice, Ross L.
United States, Seattle
Fred Hutchinson Cancer Research Center
Tjønneland, A. Marie
Denmark, Copenhagen
Institute of Cancer Epidemiology - Denmark
Vitolins, Mara Z.
United States, Winston Salem
Wake Forest University School of Medicine
Wassertheil-Smoller, Silvia
United States, New York
Albert Einstein College of Medicine of Yeshiva University
Strickler, Howard D.
United States, New York
Albert Einstein College of Medicine of Yeshiva University
Rod, Naja Hulvej
Denmark, Copenhagen
Københavns Universitet
Statistics
Citations: 52
Authors: 15
Affiliations: 11
Identifiers
Doi:
10.1158/1055-9965.EPI-12-0310
ISSN:
10559965
Research Areas
Cancer
Environmental
Noncommunicable Diseases
Substance Abuse
Study Design
Cohort Study
Participants Gender
Female