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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #351237

Research Project: Nutritional Metabolism in Mothers, Infants, and Children

Location: Children's Nutrition Research Center

Title: Genetic variation in sensitivity to estrogens and breast cancer risk

item Jerry, D. Joseph - University Of Massachusetts
item Shull, James D - University Of Wisconsin
item Hadsell, Darryl - Children'S Nutrition Research Center (CNRC)
item Rijnkels, Monique - Texas A&M University
item Dunphy, Karen - University Of Massachusetts
item Schneider, Sallie - Baystate Medical Center
item Vandenberg, Laura - University Of Massachusetts
item Majhi, Prabin - University Of Massachusetts
item Byrne, Celia - Uniformed Services University
item Trentham-dietz, Amy - University Of Wisconsin

Submitted to: Mammalian Genome
Publication Type: Review Article
Publication Acceptance Date: 1/18/2018
Publication Date: 2/27/2018
Citation: Jerry, D., Shull, J., Hadsell, D.L., Rijnkels, M., Dunphy, K.A., Schneider, S.S., Vandenberg, L.N., Majhi, P.D., Byrne, C., Trentham-Dietz, A. 2018. Genetic variation in sensitivity to estrogens and breast cancer risk. Mammalian Genome.

Interpretive Summary:

Technical Abstract: Breast cancer risk is intertwined with exposure to estrogens. While more than 160 breast cancer risk loci have been identified in humans, genetic interactions with estrogen exposure remain to be established. Strains of rodents exhibit striking differences in their responses to endogenous ovarian estrogens (primarily 17beta-estradiol). Similar genetic variation has been observed for synthetic estrogen agonists (ethinyl estradiol) and environmental chemicals that mimic the actions of estrogens (xenoestrogens). This review of literature highlights the extent of variation in responses to estrogens among strains of rodents and compiles the genetic loci underlying pathogenic effects of excessive estrogen signaling. Genetic linkage studies have identified a total of the 35 quantitative trait loci (QTL) affecting responses to 17beta-estradiol or diethylstilbestrol in five different tissues. However, the QTL appear to act in a tissue-specific manner with 9 QTL affecting the incidence or latency of mammary tumors induced by 17beta-estradiol or diethylstilbestrol. Mammary gland development during puberty is also exquisitely sensitive to the actions of endogenous estrogens. Analysis of mammary ductal growth and branching in 43 strains of inbred mice identified 20 QTL. Regions in the human genome orthologous to the mammary development QTL harbor loci associated with breast cancer risk or mammographic density. The data demonstrate extensive genetic variation in regulation of estrogen signaling in rodent mammary tissues that alters susceptibility to tumors. Genetic variants in these pathways may identify a subset of women who are especially sensitive to either endogenous estrogens or environmental xenoestrogens and render them at increased risk of breast cancer.