Replication of breast cancer GWAS susceptibility loci in the Women's Health Initiative African American SHARe Study.
Replication of breast cancer GWAS susceptibility loci in the Women's Health Initiative African American SHARe Study.
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DOI：
10.1158/1055-9965.epi-11-0524
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发表时间：
2011-09
期刊：
影响因子：
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通讯作者：
Peters U
中科院分区：
文献类型：
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作者：
Hutter CM;Young AM;Ochs-Balcom HM;Carty CL;Wang T;Chen CT;Rohan TE;Kooperberg C;Peters U
全基因组关联研究（GWAS）已经确定了与乳腺癌风险相关的基因座。这些研究主要在欧洲血统的人群中进行。为了充分了解这些基因座的影响，重要的是要研究其他遗传祖先的群体，包括非洲裔美国妇女。我们检查了22个单核苷酸多态性（SNP），以前确定的GWAS的乳腺癌风险在欧洲和亚洲血统的妇女（索引SNP）和SNP在周围地区的研究7,800名非洲裔美国妇女（包括316名妇女与事件浸润性乳腺癌）从妇女的健康倡议SNP健康协会资源。两个索引SNP与乳腺癌相关：16q12.2/TOX 3处的rs3803662（T等位基因的HR =0.79，95% CI：0.67-0.92，p=0.003）和5 p12处的rs 10941679（G等位基因的HR =1.31，95% CI：1.06-1.63，p=0.014）。当我们扩展到区域时，3p24.1区域显示与乳腺癌风险相关（基于排列的p值=0.027），三个区域（10p15.1，10q26.13/FGFR 2和16q12.2/TOX 3）显示出相关趋势。我们的研究结果提供的证据表明，一些乳腺癌GWAS区域可能与非裔美国妇女的乳腺癌有关。需要更大，更全面的研究来充分评估已发表的GWAS研究结果的普遍性，并确定非洲裔美国人人群中潜在的新关联。已发表的GWAS结果在其他祖先群体中的复制和缺乏复制都提供了这种疾病遗传病因学的重要信息，并可能影响GWAS结果在临床和公共卫生环境中的转化。
Genome-wide association studies (GWAS) have identified loci associated with risk of breast cancer. These studies have primarily been conducted in populations of European descent. To fully understand the impact of these loci, it is important to study groups with other genetic ancestries, including African American women. We examined 22 single nucleotide polymorphisms (SNPs) previously identified in GWAS of breast cancer risk in European and Asian descent women (index SNPs) and SNPs in the surrounding regions in a study of 7,800 African American women (including 316 women with incident invasive breast cancer) from the Women’s Health Initiative SNP Health Association Resource. Two index SNPs were associated with breast cancer: rs3803662 at 16q12.2/TOX3 (HR for the T allele=0.79, 95% CI: 0.67–0.92, p=0.003) and rs10941679 at 5p12 (HR for the G allele=1.31, 95% CI: 1.06–1.63, p=0.014). When we expanded to regions, the 3p24.1 region showed an association with breast cancer risk (permutation based p-value =0.027) and three regions (10p15.1, 10q26.13/FGFR2 and 16q12.2/TOX3) showed a trend towards association. Our findings provide evidence that some breast cancer GWAS regions may be associated with breast cancer in African American women. Larger, more comprehensive studies are needed to fully assess generalizability of published GWAS findings, and to identify potential novel associations in African American populations. Both replication and lack of replication of published GWAS findings in other ancestral groups provides important information of the genetic etiology of this disease, and may impact translation of GWAS findings to clinical and public health settings.