title: Association of candidate genetic variations with gastric cardia adenocarcinoma in Chinese population: a multiple interaction analysis.
abstract: 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 × 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.
authors.affiliation: Department of Epidemiology and Biostatistics and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Chen
authors.initials: C
authors.lastname: Wu
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Zhong
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.forename: Shengyu
authors.initials: S
authors.lastname: Duan
authors.forename: Jiao
authors.initials: J
authors.lastname: Lou
authors.forename: Dianke
authors.initials: D
authors.lastname: Yu
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.forename: Tangchun
authors.initials: T
authors.lastname: Wu
authors.forename: Shaofa
authors.initials: S
authors.lastname: Nie
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Miao
authors.forename: Dongxin
authors.initials: D
authors.lastname: Lin
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D044466:Asian People / Q000235:genetics*; D002299:Cardia / Q000473:pathology*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D004273:DNA, Neoplasm / Q000235:genetics; D053222:Fas Ligand Protein / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D008875:Middle Aged; D058011:Multifactor Dimensionality Reduction; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D019014:fas Receptor / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D019014:fas Receptor; D020778:Matrix Metalloproteinase 2