Correlation between genetic polymorphisms within IL-1B and TLR4 genes and cancer risk in a Russian population: a case-control study.
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 of multiple 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.
Research Institute for Complex Issues of Cardiovascular Diseases under the Siberian Branch of the Russian Academy of Medical Sciences, Kemerovo, Russia.
Anton G
AG
Kutikhin
Arseniy E
AE
Yuzhalin
Alexey N
AN
Volkov
Alexey S
AS
Zhivotovskiy
Elena B
EB
Brusina
D000368:Aged; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000209:etiology / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000209:etiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012004:Rectal Neoplasms / Q000209:etiology / Q000235:genetics; D012306:Risk; D012426:Russia; D013274:Stomach Neoplasms / Q000209:etiology / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics*
D053583:Interleukin-1beta; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4