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Innate Immunity Pathways and Breast Cancer Risk in African American and European-American Women in the Women's Circle of Health Study (WCHS)

机译:《妇女健康圈研究》(WCHS)中非裔和欧美妇女的先天免疫途径和乳腺癌风险

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摘要

African American (AA) women are more likely than European American (EA) women to be diagnosed with early, aggressive breast cancer. Possible differences in innate immune pathways (e.g., inflammatory responses) have received little attention as potential mechanisms underlying this disparity. We evaluated distributions of selected genetic variants in innate immune pathways in AA and EA women, and examined their associations with breast cancer risk within the Women's Circle of Health Study (WCHS). In stage I of the study (864 AA and 650 EA women) we found that genotype frequencies for 35 of 42 tested SNPs (18 candidate genes) differed between AAs and EAs (corroborated by ancestry informative markers). Among premenopausal AA women, comparing variant allele carriers to non-carriers, reduced breast cancer risk was associated with CXCL5-rs425535 (OR=0.61, P=0.02), while among EA women, there were associations with TNFA-rs1799724 (OR =2.31, P =0.002) and CRP-rs1205 (OR=0.54, P=0.01). For postmenopausal women, IL1B-rs1143627 (OR=1.80, P=0.02) and IL1B-rs16944 (OR=1.85, P =0.02) were associated with risk among EA women, with significant associations for TNFA-rs1799724 limited to estrogen receptor (ER) positive cancers (OR=2.0, P =0.001). However, none of the SNPs retained significance after Bonferroni adjustment for multiple testing at the level of P0.0012 (0.05/42) except for TNFA-rs1799724 in ER positive cancers. In a stage II validation (1,365 AA and 1,307 EA women), we extended evaluations for four SNPs (CCL2-rs4586, CRP-rs1205, CXCL5-rs425535, and IL1RN-rs4251961), which yielded similar results. In summary, distributions of variants in genes involved in innate immune pathways were found to differ between AA and EA populations, and showed differential associations with breast cancer according to menopausal or ER status. These results suggest that immune adaptations suited to ancestral environments may differentially influence breast cancer risk among EA and AA women. © 2013 gong et al.
机译:非裔美国人(AA)妇女比欧洲裔美国人(EA)妇女更有可能被诊断出患有早期侵袭性乳腺癌。由于存在这种差异的潜在机制,先天免疫途径的可能差异(例如炎症反应)很少受到关注。我们评估了AA和EA妇女固有免疫途径中所选遗传变异的分布,并在妇女健康研究小组(WCHS)中检查了它们与乳腺癌风险的关联。在研究的第一阶段(864名AA和650名EA女性),我们发现42个测试的SNP中的35个(18个候选基因)的基因型频率在AA和EA之间有所不同(由祖先的信息标记证实)。在绝经前AA妇女中,比较变异等位基因携带者与非携带者,乳腺癌风险降低与CXCL5-rs425535相关(OR = 0.61,P = 0.02),而在EA女性中,与TNFA-rs1799724相关(OR = 2.31) ,P = 0.002)和CRP-rs1205(OR = 0.54,P = 0.01)。对于绝经后妇女,IL1B-rs1143627(OR = 1.80,P = 0.02)和IL1B-rs16944(OR = 1.85,P = 0.02)与EA妇女中的风险相关,TNFA-rs1799724与雌激素受体(ER)的相关性显着。 )阳性癌症(OR = 2.0,P = 0.001)。然而,除了ERA阳性癌症中的TNFA-rs1799724外,在Bonferroni调整后,没有任何一个SNP可以在P0.0012(0.05 / 42)的水平上进行多次检测,从而保持了显着性。在II期验证(1,365名AA和1,307名EA女性)中,我们扩展了对四个SNP(CCL2-rs4586,CRP-rs1205,CXCL5-rs425535和IL1RN-rs4251961)的评估,结果相似。总而言之,发现与先天免疫途径有关的基因中的变体分布在AA和EA人群之间有所不同,并且根据更年期或ER状态显示出与乳腺癌的差异关联。这些结果表明,适合祖传环境的免疫适应可能会不同地影响EA和AA妇女的乳腺癌风险。 ©2013 gong等。

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