Journal Article

Association of candidate genetic variations with gastric cardia adenocarcinoma in Chinese population: a multiple interaction analysis

Li Liu, Chen Wu, Ying Wang, Rong Zhong, Feng Wang, Xuemei Zhang, Shengyu Duan, Jiao Lou, Dianke Yu, Wen Tan, Jing Yuan, Tangchun Wu, Shaofa Nie, Xiaoping Miao and Dongxin Lin

in Carcinogenesis

Volume 32, issue 3, pages 336-342
Published in print March 2011 | ISSN: 0143-3334
Published online December 2010 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgq264
Association of candidate genetic variations with gastric cardia adenocarcinoma in Chinese population: a multiple interaction analysis

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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 (Ptrend = 4.736 × 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.

Journal Article.  5314 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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