Genetic variation in estrogen and progesterone pathway genes and breast cancer risk: an exploration of tumor subtype-specific effects
Cancer causes & control : CCC(2014)
摘要
Purpose To determine whether associations between estrogen pathway-related 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 ), 3-beta hydroxysteroid dehydrogenase type I ( HSD3B1 ), 17-beta hydroxysteroid dehydrogenase type II ( HSD17B2 ), progesterone receptor ( PGR ), and sex hormone-binding globulin ( SHBG ) and breast cancer risk in a case–control study in North Carolina. Methods Cases ( n = 1,972) were women 20–74 years old and diagnosed with breast cancer between 1993 and 2001. Population-based controls ( n = 1,776) 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; two-sided p values <3.3 × 10 −4 were statistically significant. Heterogeneity tests comparing the two most common subtypes, luminal A ( n = 679) and basal-like ( n = 200), were based on the Wald statistic. Results ESR1 rs6914211 (AA vs. AT+TT, OR 2.24, 95 % CI 1.51–3.33), ESR1 rs985191 (CC vs. AA, OR 2.11, 95 % CI 1.43–3.13), and PGR rs1824128 (TT+GT vs. GG, OR 1.33, 95 % CI 1.14–1.55) were associated with risk after accounting for multiple comparisons. Rs6914211 and rs985191 were in strong linkage disequilibrium among controls (African-Americans r 2 = 0.70; whites r 2 = 0.95). There was no evidence of heterogeneity between luminal A and basal-like subtypes, and the three SNPs were also associated with elevated risk of the less common luminal B, HER2+/ER−, and unclassified subtypes. Conclusions ESR1 and PGR SNPs were associated with risk, but lack of heterogeneity between subtypes suggests variants in hormone-related genes may play similar roles in the etiology of breast cancer molecular subtypes.
更多查看译文
关键词
Breast cancer, Single nucleotide polymorphisms, Estrogen receptor, Progesterone receptor, Cytochrome P450 family 19 subfamily A polypeptide 1, 17-Beta hydroxysteroid dehydrogenase type II, Sex hormone-binding globulin, 3-Beta hydroxysteroid dehydrogenase type I
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要