Genetic variants associated with breast-cancer risk: comprehensive research synopsis, meta-analysis, and epidemiological evidence.
Genetic variants associated with breast-cancer risk: comprehensive research synopsis, meta-analysis, and epidemiological evidence.
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DOI：
10.1016/s1470-2045(11)70076-6
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发表时间：
2011-05
期刊：
影响因子：
51.1
通讯作者：
Zheng, Wei
中科院分区：
文献类型：
--
作者：
Zhang, Ben;Beeghly-Fadiel, Alicia;Long, Jirong;Zheng, Wei
在过去的二十年里，关于候选基因的遗传变异与乳腺癌风险之间的关系，已经发表了1000多份报告。结果普遍不一致。我们进行了文献检索和荟萃分析，以提供目前对乳腺癌风险遗传结构的理解的现场概要。2010年2月28日或之前，在PubMed上分两个阶段进行了乳腺癌风险候选基因关联研究的系统文献检索。共确定了24 500份出版物，其中1 059份被认为有资格列入。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可用的数据源。通过荟萃分析，使用威尼斯标准评估具有显著相关性的变异，并将其分为与乳腺癌风险相关的强、中、弱累积证据。40个基因中的51个变异显示出与乳腺癌风险有统计学意义的显著关联。累积的流行病学证据表明，6个基因（ATM、CASP8、CHEK2、CTLA4、NBN和TP53）的10个变异与乳腺癌风险的相关性为强，4个基因（ATM、CYP19A1、TERT和XRCC3）的4个变异与乳腺癌风险的相关性为中等，另外37个变异与乳腺癌风险的相关性为弱。此外，在包括至少10,000例病例和10,000个对照的荟萃分析中，在37个基因中的45个变异中发现了与乳腺癌风险无关的令人信服的证据。虽然在之前的候选基因研究中评估的大多数基因变异在荟萃分析中显示与乳腺癌风险没有关联，但9个基因中的14个变异被发现与乳腺癌风险有中等到强烈的关联。对这些变体的进一步评估是有必要的。
Over 1,000 reports have been published during the past two decades on associations between genetic variants in candidate genes and breast cancer risk. Results have been generally inconsistent. We conducted literature searches and meta-analyses to provide a field synopsis of the current understanding of the genetic architecture of breast cancer risk. Systematic literature searches for candidate gene association studies of breast cancer risk were conducted in two stages using PubMed on or before February 28, 2010. A total of 24,500 publications were identified, of which, 1,059 were deemed eligible for inclusion. Meta-analyses were conducted for 279 genetic variants in 128 candidate genes or chromosomal loci that had a minimum of three data sources available. 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. Fifty-one variants in 40 genes showed statistically significant associations with breast cancer risk. Cumulative epidemiologic evidence for an association with breast cancer risk was graded as strong for 10 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 additional 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. While most genetic variants evaluated in previous candidate gene studies showed no association with breast cancer risk in meta-analyses, 14 variants in 9 genes were found to have moderate to strong evidence for an association with breast cancer risk. Further evaluation of these variants is warranted.