Correlation between genetic polymorphisms within IL-1B and TLR4 genes and cancer risk in a Russian population: A case-control study

Abstract

In the last decade, a growing interest has been devoted to the evaluation of the impact of single nucleotide polymorphisms (SNP) on cancer risk. According to the results ofmultiple studies, among the genes that have a considerable influence on cancer risk are those encoding pattern recognition receptors, cytokines, and antioxidant defense enzymes. Nonetheless, the effect of numerous SNPs within these genes on cancer risk has been scarcely investigated. A case-control study of 401 cases and 300 sex- and age-matched controls was performed in order to explore the role of IL1B-1473G/C (rs1143623), SOD1-7958A/G (rs4998557), TLR4-1196C/T (rs4986791), IL10-1082A/G (rs1800896), IL17A-197G/A (rs2275913), and TLR4-896A/G (rs4986790) polymorphisms in the susceptibility to colorectal cancer (n=244), gastric carcinoma (n=72), and ovarian cancer (n=85). The analysis revealed a significant relationship between the presence of heterozygous genotypes for IL1B-1473G/C and TLR4-896A/G polymorphisms and higher risk of rectal cancer (codominant model, OR=1.67; 95% CI, 1.06-2.63; p=0.048 and OR=2.25; 95% CI, 1.26-4.02; p=0.014, respectively). In addition, the variant G/G genotype of the IL10-1082A/G SNP was associated with a 2.5-fold increase in ovarian cancer risk with a borderline significance (codominant model, OR=2.45; 95% CI, 1.14-5.25; p=0.069). Similarly, the carriers of the C/T genotype for the TLR4-1196C/T polymorphism were more susceptible to rectal cancer with a borderline significance (codominant model, OR=1.42; 95% CI, 0.80-2.51 p=0.06). No statistically significant associations were found when stratifying the sample by subgroups of age, sex, and clinicopathological characteristics. Finally, we observed six combinations of haplotypes for the examined SNPs, each of which either profoundly increased or decreased cancer risk. The results from our study provided evidence that IL1B-1473G/C and TLR4-896A/G SNPs are implicated in rectal cancer development in a Russian population. Further research should be addressed to clarify the role of the abovementioned polymorphisms in cancer etiology. © International Society of Oncology and BioMarkers (ISOBM) 2014.