Association of candidate genetic variations with gastric cardia adenocarcinoma in Chinese population: a multiple interaction analysis
Association of candidate genetic variations with gastric cardia adenocarcinoma in Chinese population: a multiple interaction analysis
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DOI：
10.1093/carcin/bgq264
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发表时间：
2011-03-01
期刊：
影响因子：
4.7
通讯作者：
Lin, Dongxin
中科院分区：
文献类型：
--
作者：
Liu, Li;Wu, Chen;Lin, Dongxin
单一遗传变异可能对贲门腺癌（GCA）的风险只有适度的影响，因为这种恶性肿瘤被认为是多种遗传和环境因素复杂相互作用的结果。然而，使用参数分析方法表征多重相互作用一直是一个挑战。本研究采用logistic回归（LR）、多因素降维（MDR）和分类回归树（CART）相结合的多分析策略，在344例GCA患者和324例对照中探讨了吸烟与12种不同致癌过程的多态性之间的高阶相互作用。LR、MDR和CART分析一致表明MMP-2 C-1306T多态性是GCA风险的最强个体因素。有趣的是，MDR、LR和CART分析一致地确定了高阶相互作用。在MDR分析中，MMP-2 C-1306T、FASL T-844C和FAS G-1377A三因素模型的检测精度最高，为0.632。当用LR分析这三种多态性的联合效应时，观察到显著的基因剂量效应，优势比（or）随着危险基因型数量的增加而增加（p趋势= 4.736 × 10(-12)）。在CART分析中，携带MMP-2 -1306CC、FASL-844TT或TC和FAS -1377AA组合基因型的个体患GCA的风险最高（or = 4.58, 95%可信区间为2.07-10.14），而携带mmp -1306CT或TT基因型的风险最低。这些结果表明，MMP-2 C-1306T多态性是GCA的重要危险因素，MMP-2、FASL和FAS多态性之间的多因素相互作用在GCA的发生发展中起着更重要的作用。
Single genetic variation may only have a modest effect on risk of gastric cardia adenocarcinoma (GCA) because this malignancy is believed to result from complex interactions among multiple genetic and environmental factors. However, it has been a challenge to characterize multiple interactions using parametric analytic approaches. This study utilized a multi-analytic strategy combining logistic regression (LR), multifactor dimensionality reduction (MDR) and classification and regression tree (CART) approaches to explore high-order interactions among smoking and 12 polymorphisms involved in different processes of carcinogenesis in 344 GCA patients and 324 controls. LR, MDR and CART analyses consistently suggested MMP-2 C-1306T polymorphism as the strongest individual factor for GCA risk. Intriguingly, a high-order interaction was consistently identified by MDR, LR and CART analyses. In MDR analysis, the three-factor model including MMP-2 C-1306T, FASL T-844C and FAS G-1377A yielded the highest testing accuracy of 0.632. When analysing combined effect of these three polymorphisms by LR, a significant gene dose effect was observed with the odds ratios (ORs) being increased with increasing numbers of risk genotypes (P-trend = 4.736 x 10(-12)). In CART analysis, individuals carrying the combined genotypes of MMP-2 -1306CC, FASL-844TT or TC and FAS -1377AA had the highest risk for GCA (OR = 4.58; 95% confidence interval, 2.07-10.14) compared with the lowest risk carriers of the MMP-2 -1306CT or TT genotype. These results suggest that MMP-2 C-1306T polymorphism is an important risk factor for GCA and the multifactor interactions among polymorphisms in MMP-2, FASL and FAS play more important role in the development of GCA.