Department of Cancer Prevention & Control, Roswell Park Cancer Institute, Buffalo, NY, USA,
Breast Cancer Res Treat. 2013 Oct;141(3):447-59. doi: 10.1007/s10549-013-2698-4. Epub 2013 Sep 24.
MicroRNAs (miRNAs) are an integral part of the post-transcriptional machinery of gene expression and have been implicated in the carcinogenic cascade. Single nucleotide polymorphisms (SNPs) in miRNAs and risk of breast cancer have been evaluated in populations of European or Asian ancestry, but not among women of African ancestry. Here we examined 145 SNPs in six miRNA processing genes and in 78 miRNAs which target genes known to be important in breast cancer among 906 African American (AA) and 653 European American (EA) cases and controls enrolled in the Women's Circle of Health Study. Allele frequencies of most SNPs (87 %) differed significantly by race. We found a number of SNPs in miRNAs and processing genes in association with breast cancer overall or stratified by estrogen receptor (ER) status. Several associations were significantly different by race, with none of the associations being significant in both races. Using a polygenic risk score to combine the effects of multiple SNPs, we found significant associations with the score in each subgroup analysis. For ER-positive cancer, each unit increment of the risk score was associated with a 51 % increased risk in AAs (OR = 1.51, 95 % CI = 1.30-1.74, p = 3.3 × 10(-8)) and a 73 % increased risk in EAs (OR = 1.73, 95 % CI = 1.45-2.06, p = 1.4 × 10(-9)). These data show, for the first time, that miRNA-related genetic variations may underlie the etiology of breast cancer in both populations of African and European ancestries. Future studies are needed to validate our findings and to explore the underlying mechanisms.
微小 RNA（miRNAs）是基因表达转录后机制的一个组成部分，并且与致癌级联反应有关。miRNAs 中的单核苷酸多态性（SNPs）与乳腺癌风险已在欧洲或亚洲人群中进行了评估，但在非洲裔人群中尚未进行评估。在此，我们在 906 名非裔美国（AA）和 653 名欧裔美国（EA）病例和对照者中，研究了 6 个 miRNA 加工基因和 78 个靶向已知在乳腺癌中重要的基因的 miRNA 中的 145 个 SNPs。大多数 SNPs（87%）的等位基因频率按种族差异显著。我们发现 miRNA 和加工基因中的多个 SNPs 与乳腺癌总体或按雌激素受体（ER）状态分层相关。有几个关联按种族显著不同，在两个种族中都没有关联具有统计学意义。使用多基因风险评分来组合多个 SNPs 的效应，我们在每个亚组分析中都发现了与评分显著相关的情况。对于 ER 阳性癌症，风险评分每增加一个单位，AA 中癌症风险增加 51%（OR=1.51，95%CI=1.30-1.74，p=3.3×10(-8)），EA 中癌症风险增加 73%（OR=1.73，95%CI=1.45-2.06，p=1.4×10(-9)）。这些数据首次表明，miRNA 相关的遗传变异可能是非洲和欧洲血统人群乳腺癌发病机制的基础。需要进一步的研究来验证我们的发现并探索潜在的机制。
