Main Organiser

Julius Centre University of Malaya

Co-organiser

Department of Social and Preventive Medicine, Faculty of Medicine, University of Malay

Supported by

University of Malaya

CASP3, CASP9 POLYMORPHISMS AND THEIR SNP-SNP INTERACTION MAY INFLUENCE STOMACH CANCER RISK

Author

Ni Qin

Institution

Beijing Novartis Pharma Co. Ltd

Abstract

Objectives: Our aim is to explore the association between CASP3, CASP9 polymorphisms, their SNP- SNP interaction and the risk of stomach cancer.

Methods: 278 cases with stomach cancer and 278 gender and age (±5 years) matched controls were recruited. 8 SNPs were selected including 7 tagging SNPs (3 in CASP3, 4 in CASP9) and 1 functional SNP (1 in CASP3). We performed polymerase chain reaction-restriction fragment length polymorphism method to determine the genotypes. Logistic regression, multifactor dimensionality reduction (MDR) and polymorphism interaction analysis (PIA) were used to estimate the SNP-SNP interaction.

Results: The CASP3 polymorphisms were associated with increased stomach cancer risk (rs4647693: ORGA/AA vs. GG =1.58, 95%CI=1.09- 2.30; rs4647610: ORAG vs. AA=1.63, 95%CI=1.13- 2.34; ORGG vs. AA=2.41, 95%CI=1.32-4.43; rs12108497: ORTC vs. TT=1.53, 95%CI=1.07-2.30; ORCC vs. TT=2.30, 95%CI=1.22-4.36). CASP9 variants were not related to stomach cancer. The consistent results from MDR and PIA revealed a robust SNP-SNP interaction between CASP3 rs4647693 and CASP9 rs4646018 (P=0.011 in MDR; 1st ranking score in PIA). The interaction was confirmed as an antagonist one (OR=0.29, 95%CI=0.13-0.64) in logistic model.

Conclusion: Our findings suggest that CASP3 polymorphisms may increase the risk of stomach cancer, and there is an antagonist SNP-SNP interaction between CASP3 rs4647693 and CASP9 rs4646018.