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DNA repair polymorphisms modify bladder cancer risk: A multi-factor analytic strategy

机译:DNA修复多态性改变膀胱癌风险:多因素分析策略

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Objectives: A number of common non-synonymous single nucleotide polymorphisms ( SNPs) in DNA repair genes have been reported to modify bladder cancer risk. These include: APE1-Asn148Gln, XRCC1- Arg399Gln and XRCC1-Arg194Trp in the BER pathway, XPD- Gln751Lys in the NER pathway and XRCC3- Thr241Met in the DSB repair pathway. Methods: To examine the independent and interacting effects of these SNPs in a large study group, we analyzed these genotypes in 1,029 cases and 1,281 controls enrolled in two case- control studies of incident bladder cancer, one conducted in New Hampshire, USA and the other in Turin, Italy. Results: The odds ratio among current smokers with the variant XRCC3-241 ( TT) genotype was 1.7 ( 95% Cl 1.0 - 2.7) compared to wildtype. We evaluated gene- environment and gene- gene interactions using four analytic approaches: logistic regression, Multifactor Dimensionality Reduction ( MDR), hierarchical interaction graphs, classification and regression trees ( CART), and logic regression analyses. All five methods supported a gene- gene interaction between XRCC1- 399/ XRCC3- 241 ( p = 0.001) ( adjusted OR for XRCC1- 399 GG, XRCC3- 241 TT vs. wildtype 2.0 ( 95% Cl 1.4 - 3.0)). Three methods predicted an interaction between XRCC1- 399/ XPD- 751 ( p = 0.008) ( adjusted OR for XRCC1- 399 GA or AA, XRCC3- 241 AA vs. wild- type 1.4 ( 95% Cl 1.1 - 2.0)). Conclusions: These results support the hypothesis that common polymorphisms in DNA repair genes modify bladder cancer risk and highlight the value of using multiple complementary analytic approaches to identify multi- factor interactions. Copyright (C) 2007 S. Karger AG, Basel.
机译:目的:已经报道了DNA修复基因中许多常见的非同义单核苷酸多态性(SNP)会改变膀胱癌的风险。它们包括:BER途径中的APE1-Asn148Gln,XRCC1-Arg399Gln和XRCC1-Arg194Trp,NER途径中的XPD-Gln751Lys和DSB修复途径中的XRCC3-Thr241Met。方法:为了在一个大型研究组中研究这些SNP的独立和相互作用,我们分析了参与两个关于膀胱癌的病例对照研究(分别在美国新罕布什尔州和另一个国家进行)的1,029例病例和1,281例对照的基因型在意大利都灵。结果:与野生型相比,当前具有变异XRCC3-241(TT)基因型的吸烟者的优势比为1.7(95%Cl 1.0-2.7)。我们使用四种分析方法评估了基因-环境和基因-基因之间的相互作用:逻辑回归,多因素降维(MDR),层次交互图,分类和回归树(CART)以及逻辑回归分析。所有这五种方法均支持XRCC1-399 / XRCC3-241之间的基因-基因相互作用(p = 0.001)(针对XRCC1-399 GG,XRCC3-241 TT与野生型2.0(95%Cl 1.4-3.0)进行校正或。三种方法预测了XRCC1-399 / XPD-751之间的相互作用(p = 0.008)(对于XRCC1-399 GA或AA,XRCC3-241 AA与野生型1.4(95%Cl 1.1-2.0)进行了校正或)。结论:这些结果支持以下假设:DNA修复基因中的常见多态性会改变膀胱癌的风险,并突出了使用多种互补分析方法鉴定多因素相互作用的价值。版权所有(C)2007 S.Karger AG,巴塞尔。

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