Polymorphisms in human telomerase reverse transcriptase (hTERT) gene, gene- gene and gene-smoking interaction with susceptibility to gastric cancer in Chinese Han population

Abstract

AimsTo investigate the association of telomerase reverse transcriptase (TERT) gene polymorphisms and additional gene-gene and gene- environment interaction with gastric cancer (GC) risk.ResultsGC 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 MethodsA 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.ConclusionsWe 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.

Genetic polymorphisms in human telomerase reverse transcriptase (hTERT) gene polymorphisms do not associated with breast cancer in patients in a turkish population: hospital-based case-control study

“…Hashemi et al sug-gested that the hTERT rs2736098 variant influence the risk of BC in an Iranian population in southeast Iran (20). Zhang et al 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 gastric cancer risk (21). Both of these two studies disagree with our findings.…”

Association between functional TERT promoter polymorphism rs2853669 and cervical cancer risk in South Indian women

“…Meta-analysis results. Based on the inclusion criteria, a total of 17 studies from 14 previously published articles (15,(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) along with the present study results were analyzed for the association between the TERT rs2583669 polymorphism and cancer susceptibility; this included 9,537 cancer cases and 12,370 controls (Table V). By pooling all the previous studies, a statistically significant association between the TERT rs2583669 polymorphism and cancer risk was identified (dominant model: Pooled OR=1.09; 95% CI, 1.03-1.16; P=0.004; Fig.…”

SNP interactions of PGC with its neighbor lncRNAs enhance the susceptibility to gastric cancer/atrophic gastritis and influence the expression of involved molecules

“…The carcinogenic effect of tobacco smoke on various organs is well recognized, and it accounts for about 50% increase in GC risk . Previously, lots of studies have investigated the interaction between other genes and smoking on GC, including TNF, Exo1, CYP1A1, IL‐10, ERCC8, GSTP1, and hTERT . They all suggest genetic effects of gene polymorphisms on gastric carcinogenesis can be exacerbated by cigarette smoking.…”

“…21,22 Previously, lots of studies have investigated the interaction between other genes and smoking on GC, including TNF, Exo1, CYP1A1, IL-10, ERCC8, GSTP1, and hTERT. [23][24][25][26][27][28][29] They all suggest genetic effects of gene polymorphisms on gastric carcinogenesis can be exacerbated by cigarette smoking. Here, the interactions of PGC rs9471643 and lnc-C6orf-132-1 rs7749023/ rs7747696 on AG risk could also be affected by smoking, although the mechanism has not been understood.…”