Genetic variants in hypothalamic-pituitary-adrenal axis genes and breast cancer risk in Caucasians and African Americans.
Genetic variants in hypothalamic-pituitary-adrenal axis genes and breast cancer risk in Caucasians and African Americans.
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发表时间：
2015-09
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通讯作者：
H. Nan;J. Dorgan;T. Rebbeck
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作者：
H. Nan;J. Dorgan;T. Rebbeck
在前瞻性研究中，肾上腺雄激素脱氢表雄酮(DHEA)及其硫酸盐(DHEAS)的循环水平升高与乳腺癌风险增加相关。下丘脑-垂体-肾上腺(HPA)轴基因的遗传变异可能有助于这些循环激素水平，从而增加乳腺癌的风险。以前没有研究过HPA轴基因的遗传变异对乳腺癌风险的影响。我们在女性洞察力和共享经验(WISE)研究中评估了5个HPA轴基因(NR3C1、NR3C2、CRH、CRHR1和CRHBP)上的49个单核苷酸多态(SNPs)与乳腺癌风险的关系。这些研究涉及高加索人(346例和442名对照)以及非裔美国人(149例和246名对照)。在被评估的49个SNP中，一个在白人中与乳腺癌风险有名义上的显著关联(P为Trend<；0.05)，另外两个在非裔美国人中。CRHBP基因中rs11747190[A]SNP对高加索女性乳腺癌风险的年龄调整后的相加优势比(OR)(95%可信区间，95%CI)为1.45(1.09~1.94)。两个SNP(CRHBP rs1700688[T]和CRHR1 rs17689471[C])对非裔美国女性患乳腺癌的年龄调整后的OR(95%顺式)分别为1.84(1.13~2.98)和2.48(1.20~5.13)。然而，在对多次测试进行校正后，这些SNP没有显示出显著的相关性。我们的发现没有提供强有力的证据支持这些HPA轴基因的基因变异对高加索人或非裔美国人患乳腺癌的风险的贡献。
Elevated circulating levels of the adrenal androgen dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are associated with increased breast cancer risk in prospective studies. Genetic variants in hypothalamic-pituitary-adrenal (HPA) axis genes may contribute to these circulating hormone levels, and consequently to breast cancer risk. No previous studies have examined the effects of genetic variants in HPA axis genes on breast cancer risk. We evaluated the associations of 49 single nucleotide polymorphisms (SNPs) in five HPA axis genes (NR3C1, NR3C2, CRH, CRHR1, and CRHBP) with the risk of breast cancer in the Women's Insights and Shared Experiences (WISE) Study of Caucasians (346 cases and 442 controls), as well as African Americans (149 cases and 246 controls). Of the 49 SNPs evaluated, one showed a nominal significant association (P for trend < 0.05) with breast cancer risk among Caucasians, and another two among African Americans. The age-adjusted additive odds ratio (OR) (95% confidence interval (95% CI)) of the SNP rs11747190[A] in the CRHBP gene for the risk of breast cancer among Caucasian women was 1.45 (1.09-1.94). The age-adjusted additive ORs (95% CIs) of two SNPs (CRHBP rs1700688[T] and CRHR1 rs17689471[C]) for the risk of breast cancer among African American women were 1.84 (1.13-2.98) and 2.48 (1.20-5.13), respectively. However, these SNPs did not show significant associations after correction for multiple testing. Our findings do not provide strong supportive evidence for the contribution of genetic variants in these HPA axis genes to the risk of developing breast cancer in either Caucasians or African Americans.