常见的单核苷酸多态性与乳腺癌：来自乳腺癌协会联盟的结果。

Commonly studied single-nucleotide polymorphisms and breast cancer: results from the Breast Cancer Association Consortium.

出版信息

J Natl Cancer Inst. 2006 Oct 4;98(19):1382-96. doi: 10.1093/jnci/djj374.

Abstract

BACKGROUND

The Breast Cancer Association Consortium (BCAC) is an international collaboration that was established to provide large sample sizes for examining genetic associations. We conducted combined analyses on all single-nucleotide polymorphisms (SNPs) whose associations with breast cancer have been investigated by at least three participating groups.

METHODS

Data from up to 12 studies were pooled for each SNP (ADH1C I350V, AURKA F31I, BRCA2 N372H, CASP8 D302H, ERCC2 D312N, IGFBP3 -202 c>a, LIG4 D501D, PGR V660L, SOD2 V16A, TGFB1 L10P, TP53 R72P, XRCC1 R399Q, XRCC2 R188H, XRCC3 T241M, XRCC3 5' UTR, and XRCC3 IVS7-14). Genotype frequencies in case and control subjects were compared, and genotype-specific odds ratios for the risk of breast cancer in heterozygotes and homozygotes for the rare allele compared with homozygotes for the common allele were estimated with logistic regression. Statistical tests were two-sided.

RESULTS

The total number of subjects for analysis of each SNP ranged from 12,013 to 31,595. For five SNPs--CASP8 D302H, IGFBP3 -202 c>a, PGR V660L, SOD2 V16A, and TGFB1 L10P--the associations with breast cancer were of borderline statistical significance (P = .016, .060, .047, .056, and .0088 respectively). The remaining 11 SNPs were not associated with breast cancer risk; genotype-specific odds ratios were close to unity. There was some evidence for between-study heterogeneity (P<.05) for four of the 11 SNPs (ADH1C I350V, ERCC2 D312N, XRCC1 R399Q, and XRCC3 IVS5-14).

CONCLUSION

Pooling data within a large consortium has helped to clarify associations of SNPs with breast cancer. In the future, consortia such as the BCAC will be important in the analysis of rare polymorphisms and gene x gene or gene x environment interactions, for which individual studies have low power to identify associations, and in the validation of associations identified from genome-wide association studies.

摘要

背景

乳腺癌协会联盟（BCAC）是一个国际合作组织，其成立目的是为研究基因关联提供大样本量。我们对所有单核苷酸多态性（SNP）进行了联合分析，这些SNP与乳腺癌的关联已由至少三个参与研究的小组进行过调查。

方法

针对每个SNP（ADH1C I350V、AURKA F31I、BRCA2 N372H、CASP8 D302H、ERCC2 D312N、IGFBP3 -202 c>a、LIG4 D501D、PGR V660L、SOD2 V16A、TGFB1 L10P、TP53 R72P、XRCC1 R399Q、XRCC2 R188H、XRCC3 T241M、XRCC3 5' UTR和XRCC3 IVS7-14）汇总了多达12项研究的数据。比较了病例组和对照组的基因型频率，并通过逻辑回归估计了与常见等位基因纯合子相比，杂合子和罕见等位基因纯合子患乳腺癌风险的基因型特异性比值比。统计检验为双侧检验。

结果

每个SNP分析的受试者总数在12,013至31,595之间。对于五个SNP（CASP8 D302H、IGFBP3 -202 c>a、PGR V660L、SOD2 V16A和TGFB1 L10P），其与乳腺癌的关联具有临界统计学意义（分别为P = 0.016、0.060、0.047、0.056和0.0088）。其余11个SNP与乳腺癌风险无关；基因型特异性比值比接近1。对于11个SNP中的4个（ADH1C I350V、ERCC2 D312N、XRCC1 R399Q和XRCC3 IVS5-14），有证据表明研究间存在异质性（P<0.05）。