Xue Wen-Qiong, He Yong-Qiao, Zhu Jin-Hong, Ma Jian-Qun, He Jing, Jia Wei-Hua
State Key Laboratory of Oncology in South China, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong, China.
Molecular Epidemiology Laboratory and Laboratory Medicine, Harbin Medical University Cancer Hospital, Harbin 150040, Heilongjiang, China.
Sci Rep. 2014 Oct 28;4:6791. doi: 10.1038/srep06791.
BRCA2 gene plays an important role in homologous recombination. Polymorphic variants in this gene has been suggested to confer cancer susceptibility. Numerous studies have investigated association between BRCA2 N372H polymorphism and risk of several cancers, especially breast cancer. However, the results were inconsistent. We performed a comprehensive meta-analysis to provide a more precise assessment of the association between N372H and cancer risk, following the latest meta-analysis guidelines (PRISMA). Forty six studies involving 36299 cases and 48483 controls were included in our meta-analysis. The crude ORs and the 95% CIs were used to evaluate the strength of the association. The results indicated that the BRCA2 N372H variant was significantly associated with an increased risk of overall cancer (dominant model: OR = 1.07, 95% CI = 1.01-1.13; recessive model: OR = 1.12, 95% CI = 1.02-1.23). Moreover, stratified analyses by the cancer type and source of control observed significantly increased risk associated with BRCA2 N372H in subgroups with ovarian cancer, non-Hodgkin lymphoma and population-based controls, but not breast cancer or hospital-based controls. We also found such association among Africans. Overall, the meta-analysis suggested that BRCA2 N372H may be a cancer susceptibility polymorphism. Well-designed and large-scale studies are needed to substantiate the association between BRCA2 N372H polymorphism and cancer risk.
BRCA2基因在同源重组中起重要作用。该基因的多态性变异被认为会增加癌症易感性。许多研究调查了BRCA2基因N372H多态性与几种癌症风险之间的关联，尤其是乳腺癌。然而，结果并不一致。我们按照最新的荟萃分析指南（PRISMA）进行了一项全面的荟萃分析，以更精确地评估N372H与癌症风险之间的关联。我们的荟萃分析纳入了46项研究，涉及36299例病例和48483例对照。采用粗比值比（OR）和95%置信区间（CI）来评估关联强度。结果表明，BRCA2基因N372H变异与总体癌症风险增加显著相关（显性模型：OR = 1.07，95%CI = 1.01 - 1.13；隐性模型：OR = 1.12，95%CI = 1.02 - 1.23）。此外，按癌症类型和对照来源进行的分层分析发现，在卵巢癌、非霍奇金淋巴瘤亚组以及基于人群的对照中，BRCA2基因N372H与风险显著增加相关，但在乳腺癌亚组或基于医院的对照中并非如此。我们在非洲人群中也发现了这种关联。总体而言，荟萃分析表明BRCA2基因N372H可能是一种癌症易感性多态性。需要设计良好的大规模研究来证实BRCA2基因N372H多态性与癌症风险之间的关联。
