Nucleotide Excision Repair Pathway Polymorphisms and Pancreatic Cancer Risk: Evidence for role of MMS19L
Nucleotide Excision Repair Pathway Polymorphisms and Pancreatic Cancer Risk: Evidence for role of MMS19L
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DOI：
10.1158/1055-9965.epi-08-1109
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发表时间：
2009-04-01
影响因子：
3.8
通讯作者：
Petersen, Gloria M.
中科院分区：
文献类型：
--
作者：
McWilliams, Robert R.;Bamlet, William R.;Petersen, Gloria M.
背景：核苷酸切除修复是对DNA损伤的重要反应，包括烟草暴露引起的损伤。单核苷酸多态性（SNP）在核苷酸切除修复途径可能编码的改变，影响DNA修复功能，从而影响胰腺癌development.Methods的风险：临床为基础的病例对照研究，在非西班牙裔白色人比较了1,143例胰腺癌患者与1,097名健康对照。鉴定了27个直接和间接参与核苷酸切除修复途径的基因，并从其中的26个中选择了236个tag-SNP（一个没有鉴定出SNP）。通过主成分分析在基因水平上进行关联研究，而递归分区分析用于确定途径内潜在的基因-基因和基因-环境相互作用。在个体SNP水平，调整加性，显性和隐性模型进行了调查，基因-环境相互作用也assessed.Results：基因水平分析显示，MMS 19 L基因型（染色体10q24.1）与胰腺癌的风险改变（P = 0.023）的关联。MMS 19 L单倍型分析也显示出显著的关联（P = 0.0132）。在这个基因中的7个人的SNPs的分析表明，保护和风险协会的次要等位基因，广泛分布在患者亚组定义的吸烟状况，性别和年龄。结论：在候选人的途径SNP关联研究分析，常见的变异核苷酸切除修复基因，MMS 19 L，与胰腺癌的风险。（癌症流行病学生物标志物Prev 2009;18（4）：1295-302）
Background: Nucleotide excision repair is a vital response to DNA damage, including damage from tobacco exposure. Single nucleotide polymorphisms (SNP) in the nucleotide excision repair pathway may encode alterations that affect DNA repair function and therefore influence the risk of pancreatic cancer development.Methods: A clinic-based case-control study in non-Hispanic white persons compared 1,143 patients with pancreatic adenocarcinoma with 1,097 healthy controls. Twenty-seven genes directly and indirectly involved in the nucleotide excision repair pathway were identified and 236 tag-SNPs were selected from 26 of these (one had no SNPs identified). Association studies were done at the gene level by principal components analysis, whereas recursive partitioning analysis was utilized to identify potential gene-gene and gene-environment interactions within the pathway. At the individual SNP level, adjusted additive, dominant, and recessive models were investigated, and gene-environment interactions were also assessed.Results: Gene level analyses showed an association of the MMS19L genotype (chromosome 10q24.1) with altered pancreatic cancer risk (P = 0.023). Haplotype analysis of MMS19L also showed a significant association (P = 0.0132). Analyses of seven individual SNPs in this gene showed both protective and risk associations for minor alleles, broadly distributed across patient subgroups defined by smoking status, sex, and age.Conclusion: In a candidate pathway SNP association study analysis, common variation in a nucleotide excision repair gene, MMS19L, was associated with the risk of pancreatic cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1295-302)