Polymorphisms in human telomerase reverse transcriptase (hTERT) gene, gene- gene and gene-smoking interaction with susceptibility to gastric cancer in Chinese Han population
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Jian Zhang1, Hui Ju1, Jun- Ru Gao1, Xue-Long Jiao1, Yun Lu1
1Department of General Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, People’s Republic of China
Yun Lu, email: [email protected]
Jian Zhang, email: [email protected]
Keywords: gastric cancer, TERT gene, single nucleotide polymorphisms, interaction, haplotype
Received: September 30, 2016 Accepted: January 04, 2017 Published: February 24, 2017
Aims: To investigate the association of telomerase reverse transcriptase (TERT) gene polymorphisms and additional gene-gene and gene- environment interaction with gastric cancer (GC) risk.
Results: GC risk was significantly higher in carriers of G allele of rs2736100 than those with TT genotype (TG+ GG versus TT), adjusted OR (95%CI) =1.68 (1.26-2.17), and higher in carriers of G allele of rs2853669 than those with AA genotype (AG+ GG versus AA), adjusted OR (95%CI) = 1.72 (1.19-2.33). We also found that interaction between rs2736100 and smoking was associated with higher GC risk. Smokers with TG or GG of rs2736100 genotype have elevated GC risk, compared to never- smokers with TT of rs2736100 genotype, OR (95%CI) = 3.12 (1.82 -4.61). Pairwise linkage equilibrium (LD) analysis between SNPs was measured and the D’ value between rs2736100 and rs2736109 was more than 0.8. A haplotype containing the rs2736100- G and rs2736109- A alleles was associated with a statistically increased GC risk (OR= 2.66, 95%CI= 1.28 – 4.12, p<0.0001).
Materials and Methods: A total of 1088 participants (686 males, 402 females) were selected, including 360 GC patients and 728 normal participants. Logistic regression was performed to investigate association between single nucleotide polymorphisms (SNPs) within TERT gene and GC susceptibility. Generalized multifactor dimensionality reduction (GMDR) model was used to screen gene- gene and gene- environment interaction combinations.
Conclusions: We found that G allele of rs2736100 and G allele of rs2853669 in TERT gene, interaction between rs2736100 and smoking, and haplotype containing the rs2736100- G and rs2736109- A alleles were all associated with increased GC risk.
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