Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
Lancet Oncol. 2011 May;12(5):477-88. doi: 10.1016/S1470-2045(11)70076-6. Epub 2011 Apr 20.
More than 1000 reports have been published in the past two decades on associations between variants in candidate genes and risk of breast cancer. Results have been generally inconsistent. We did a literature search and meta-analyses to provide a synopsis of the current understanding of the genetic architecture of breast-cancer risk.
A systematic literature search for candidate-gene association studies of breast-cancer risk was done in two stages, using PubMed on or before Feb 28, 2010. A total of 24,500 publications were identified, of which 1059 were deemed eligible for inclusion. Meta-analyses were done for 279 genetic variants in 128 candidate genes or chromosomal loci that had at least three data sources. Variants with significant associations by meta-analysis were assessed using the Venice criteria and scored as having strong, moderate, or weak cumulative evidence for an association with breast-cancer risk.
51 variants in 40 genes showed significant associations with breast-cancer risk. Cumulative epidemiological evidence of an association was graded as strong for ten variants in six genes (ATM, CASP8, CHEK2, CTLA4, NBN, and TP53), moderate for four variants in four genes (ATM, CYP19A1, TERT, and XRCC3), and weak for 37 variants. Additionally, in meta-analyses that included a minimum of 10,000 cases and 10,000 controls, convincing evidence of no association with breast-cancer risk was identified for 45 variants in 37 genes.
Whereas most genetic variants assessed in previous candidate-gene studies showed no association with breast-cancer risk in meta-analyses, 14 variants in nine genes had moderate to strong evidence for an association. Further evaluation of these variants is warranted.
US National Cancer Institute.
在过去的二十年中，已经发表了超过 1000 篇关于候选基因变异与乳腺癌风险之间关联的报告。结果通常不一致。我们进行了文献检索和荟萃分析，以提供对乳腺癌风险遗传结构的当前理解。
在两个阶段进行了候选基因与乳腺癌风险关联的系统文献检索，使用的是 2010 年 2 月 28 日或之前的 PubMed。总共确定了 24500 篇出版物，其中有 1059 篇被认为符合纳入标准。对 128 个候选基因或染色体位点的 279 个遗传变异进行了荟萃分析，这些基因或染色体位点至少有三个数据源。使用威尼斯标准评估通过荟萃分析具有显著相关性的变体，并将其评为与乳腺癌风险相关的强、中或弱累积证据。
在 40 个基因中的 51 个变体与乳腺癌风险显著相关。对十个变体在六个基因（ATM、CASP8、CHEK2、CTLA4、NBN 和 TP53）中的关联的累积流行病学证据被评为强，四个变体在四个基因（ATM、CYP19A1、TERT 和 XRCC3）中的关联的累积流行病学证据为中等，37 个变体的关联则较弱。此外，在至少包含 10000 例病例和 10000 例对照的荟萃分析中，37 个基因中的 45 个变体与乳腺癌风险没有关联，这一结果具有令人信服的证据。
尽管以前的候选基因研究中评估的大多数遗传变体在荟萃分析中没有显示与乳腺癌风险相关，但九个基因中的 14 个变体具有中等至强的关联证据。这些变体需要进一步评估。
美国国家癌症研究所。
