SNP-SNP interactions between DNA repair genes were associated with breast cancer risk in a Korean population
SNP-SNP interactions between DNA repair genes were associated with breast cancer risk in a Korean population
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DOI：
10.1002/cncr.26220
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发表时间：
2012-02-01
期刊：
影响因子：
6.2
通讯作者：
Kwack, KyuBum
中科院分区：
文献类型：
--
作者：
Han, Wonshik;Kim, Kyoung-Yeon;Kwack, KyuBum
背景技术背景：核苷酸切除修复（NER）通路基因的单核苷酸多态性（SNPs）可调节DNA修复能力并增加乳腺癌（BC）的易感性。通过评估参与DNA修复的基因进行病例对照研究，以确定与BC相关的多态性。方法：采用Illumina GoldenGate方法对38个候选基因的384个SNPs进行基因分型。基因型是在一项病例对照研究中确定的，该研究包括346名BC患者和361名对照。使用逻辑回归模型计算比值比和95%置信区间。多元逻辑回归模型校正年龄，家族史的BC，和身体质量指数。结果：DNA修复途径基因间的基因交互作用分析显示，DNA修复途径基因间的交互作用对乳腺癌风险有显著影响. ERCC 2 rs 50872（TC基因型）与XPA rs 2808668（TC基因型）和rs 1800975（AG基因型）的组合与BC风险增加密切相关（分别为P.0004和P.0002，PBonferroni.023和P.014）。此外，XPA中的T-G（包括rs 2808668和rs 1800975）单倍型与rs 50872携带者中的ERCC 2 T等位基因组合也与BC的加性风险效应相关（比值比：分别为2.58、2.62和3.49）。结论：与NER机制相关的DNA修复基因的遗传变异增加了BC发生的风险。这些结果表明，通过基因-基因相互作用的SNP的更强的组合效应可能有助于预测BC风险。Cancer 2012; 118：594- 602. (C)2011年美国癌症协会
BACKGROUND: Single nucleotide polymorphisms (SNPs) in nucleotide excision repair (NER) pathway genes may modulate DNA repair capacity and increase susceptibility to breast cancer (BC). A case-control study was conducted by evaluating genes involved in DNA repair to identify polymorphisms associated with BC. METHODS: The 384 SNPs of 38 candidate genes were genotyped using the Illumina GoldenGate method. Genotypes were determined in a case- control study that consisted of 346 BC patients and 361 controls. Odds ratios and 95% confidence intervals were computed using logistic regression models. Multiple logistic regression models adjusted for age, family history of BC, and body mass index were used. RESULTS: Gene- gene interaction analysis among the DNA repair pathway genes showed significant effects on BC risk. ERCC2 rs50872 (TC genotype) in combination with XPA rs2808668 (TC genotype) and rs1800975 (AG genotype) was strongly associated with an increased risk of BC (P.0004 and.0002, PBonferroni.023 and.014, respectively). Moreover, the T- G (including rs2808668 and rs1800975) haplotype in XPA combined with the ERCC2 T allele in rs50872 carriers was also associated with additive risk effect of BC (odds ratios: 2.58, 2.62, and 3.49, respectively). CONCLUSION: Genetic variation in DNA repair genes involved in NER mechanisms increased the risk of BC development. These results suggested that a stronger combined effect of SNPs via gene- gene interaction may help to predict BC risk. Cancer 2012; 118: 594- 602. (C) 2011 American Cancer Society.