Quantifying mediating effects of endogenous estrogen and insulin in the relation between obesity, alcohol consumption and breast cancer
Cancer Epidemiology, Biomarkers & Prevention, 06/04/2012
Hvidtfeldt UA et al. – The relation of BMI with breast cancer was partly mediated through estradiol and, to a greater extent, through insulin. 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
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 1601 women (601 cases) aged 50-79 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.
A 5-unit increase in BMI was associated with 50.0 (95% 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 ER+ cases.
Consuming 7+ drinks/week compared to 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.
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