Contribution of Genetic Polymorphisms of Inflammation Response Genes on Sporadic Colorectal Cancer Predisposition Risk in Malaysian Patients – A Case Control Study

Abstract

AIM: To investigate the frequencies and association of polymorphic genotypes of IL-8 -251 T>A, TNF-α -308<br />G>A, ICAM-1 K469E, ICAM-1 R241G, IL-6 -174 G>C, and PPAR-γ 34 C>G in modulating susceptibility risk in<br />Malaysian colorectal cancer (CRC) patients. Methods: In this case-control study, peripheral blood samples of 560<br />study subjects (280 CRC patients and 280 controls) were collected, DNA extracted and genotyped using PCR-RFLP<br />and Allele Specific PCR. The association between polymorphic genotype and CRC susceptibility risk was determined<br />using Logistic Regression analysis deriving Odds ratio (OR) and 95% CI. Results: On comparing the frequencies of<br />genotypes of all single nucleotide polymorphisms ( SNPs ) in patients and controls, the homozygous variant genotypes<br />IL-8 -251 AA and TNF-α -308 AA and variant A alleles were significantly higher in CRC patients. Investigation on<br />the association of the variant alleles and genotypes singly, with susceptibility risk showed the homozygous variant A<br />alleles and genotypes IL-8 -251 AA and TNF-α -308 AA to be at higher risk for CRC predisposition. Analysis based<br />on age, gender and smoking habits showed that the polymorphisms IL8 -251 T>A and TNF – α 308 G>A contribute<br />to a significantly higher risk among male and female who are more than 50 years and for smokers in this population.<br />Conclusion: We observed an association between variant allele and genotypes of IL-8-251 T>A and TNF-α-308<br />G>A polymorphisms and CRC susceptibility risk in Malaysian patients. These two SNPs in inflammatory response<br />genes which undoubtedly contribute to individual risks to CRC susceptibility may be considered as potential genetic<br />predisposition factors for CRC in Malaysian population.