Genetic variation in estrogen and progesterone pat

Authors: Sarah J Nyante Marilie D Gammon Jay S Kaufman Jeannette T Bensen Dan Yu Lin Jill S BarnholtzSloan Yijuan Hu Qianchuan He Jingchun Luo Robert C Millikan

Publish Date: 2014/11/25

Volume: 26, Issue: 1, Pages: 121-131

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Abstract

To determine whether associations between estrogen pathwayrelated single nucleotide polymorphisms SNPs and breast cancer risk differ by molecular subtype we evaluated associations between SNPs in cytochrome P450 family 19 subfamily A polypeptide 1 CYP19A1 estrogen receptor ESR1 3beta hydroxysteroid dehydrogenase type I HSD3B1 17beta hydroxysteroid dehydrogenase type II HSD17B2 progesterone receptor PGR and sex hormonebinding globulin SHBG and breast cancer risk in a case–control study in North CarolinaCases n = 1972 were women 20–74 years old and diagnosed with breast cancer between 1993 and 2001 Populationbased controls n = 1776 were frequency matched to cases by age and race A total of 195 SNPs were genotyped and linkage disequilibrium was evaluated using the r 2 statistic Odds ratios ORs and 95  confidence intervals CIs for associations with breast cancer overall and by molecular subtype were estimated using logistic regression Monte Carlo methods were used to control for multiple comparisons twosided p values 33 × 10−4 were statistically significant Heterogeneity tests comparing the two most common subtypes luminal A n = 679 and basallike n = 200 were based on the Wald statisticESR1 rs6914211 AA vs AT+TT OR 224 95  CI 151–333 ESR1 rs985191 CC vs AA OR 211 95  CI 143–313 and PGR rs1824128 TT+GT vs GG OR 133 95  CI 114–155 were associated with risk after accounting for multiple comparisons Rs6914211 and rs985191 were in strong linkage disequilibrium among controls AfricanAmericans r 2 = 070 whites r 2 = 095 There was no evidence of heterogeneity between luminal A and basallike subtypes and the three SNPs were also associated with elevated risk of the less common luminal B HER2+/ER− and unclassified subtypesThis work was supported by funding from the National Institutes of Health P50CA58223 P30CA16086 R25CA57726 to SJN P30ES10126 to M D G and R C M The authors wish to thank Patricia Basta of the University of North Carolina at Chapel Hill Epidemiology Department and Michael Andre and Amanda Beaty of the University of North Carolina Lineberger Comprehensive Cancer Center for their work preparing the DNA samples and conducting the genotyping The authors also thank Jessica Tse of the University of North Carolina at Chapel Hill Epidemiology Department for advice and statistical support

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