ABSTRACT
AIM: To investigate the frequencies and association of polymorphic genotypes of IL-8 -251 T>A, TNF-α -308 G>A, ICAM-1 K469E, ICAM-1 R241G, IL-6 -174 G>C, and PPAR-γ 34 C>G in modulating susceptibility risk in Malaysian colorectal cancer (CRC) patients. Methods: In this case-control study, peripheral blood samples of 560 study subjects (280 CRC patients and 280 controls) were collected, DNA extracted and genotyped using PCR-RFLP and Allele Specific PCR. The association between polymorphic genotype and CRC susceptibility risk was determined using Logistic Regression analysis deriving Odds ratio (OR) and 95% CI. Results: On comparing the frequencies of genotypes of all single nucleotide polymorphisms ( SNPs ) in patients and controls, the homozygous variant genotypes IL-8 -251 AA and TNF-α -308 AA and variant A alleles were significantly higher in CRC patients. Investigation on the association of the variant alleles and genotypes singly, with susceptibility risk showed the homozygous variant A alleles and genotypes IL-8 -251 AA and TNF-α -308 AA to be at higher risk for CRC predisposition. Analysis based on age, gender and smoking habits showed that the polymorphisms IL8 -251 T>A and TNF α 308 G>A contribute to a significantly higher risk among male and female who are more than 50 years and for smokers in this population. Conclusion: We observed an association between variant allele and genotypes of IL-8-251 T>A and TNF-α-308 G>A polymorphisms and CRC susceptibility risk in Malaysian patients. These two SNPs in inflammatory response genes which undoubtedly contribute to individual risks to CRC susceptibility may be considered as potential genetic predisposition factors for CRC in Malaysian population.
Subject(s)
Biomarkers, Tumor/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Genetic Predisposition to Disease , Inflammation/genetics , Inflammation/pathology , Polymorphism, Single Nucleotide , Case-Control Studies , Female , Follow-Up Studies , Genotype , Humans , Inflammation Mediators , Intercellular Adhesion Molecule-1/genetics , Interleukin-6/genetics , Interleukin-8/genetics , Male , Middle Aged , PPAR gamma/genetics , Prognosis , Promoter Regions, Genetic , Risk Factors , Tumor Necrosis Factor-alpha/geneticsABSTRACT
AIM: To investigate the allele and genotype frequencies and associated risk of interleukin (IL)-8 -251T>A polymorphism on colorectal cancer (CRC) susceptibility risk. METHODS: Peripheral blood samples of 255 normal controls and 255 clinically and histopathologically confirmed CRC patients were genotyped for IL-8 -251T>A polymorphism employing allele-specific polymerase chain reaction. The relative association of variant allele and genotypes with CRC susceptibility risk was determined by calculating the odds ratios (ORs). Corresponding χ² tests on the CRC patients and controls were carried out and 95% confidence intervals (CIs) were determined using Fisher's exact test. The allele frequencies and its risk association were calculated using FAMHAP, haplotype association analysis software. RESULTS: On comparing the frequencies of genotypes of patients and controls, the homozygous variant AA was significantly higher in CRC patients (P = 0.002) compared to controls. Investigation on the association of the polymorphic genotypes with CRC susceptibility risk, showed that the homozygous variant IL-8 -251AA had a significantly increased risk with OR 3.600 (95% CI: 1.550-8.481, P = 0.001). In the case of allele frequencies, variant allele A of IL-8 -251 showed a significantly increased risk of CRC predisposition with OR 1.32 (95% CI: 1.03-1.69, P = 0.003). CONCLUSION: Variant allele and genotype of IL-8 (-251T>A) was significantly associated with CRC susceptibility risk and could be considered as a high-risk variant for CRC predisposition.
Subject(s)
Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Interleukin-8/genetics , Polymorphism, Genetic , Adult , Aged , Alleles , Case-Control Studies , Colorectal Neoplasms/ethnology , Female , Gene Frequency , Genetic Predisposition to Disease , Genetic Variation , Genotype , Haplotypes , Humans , Malaysia , Male , Middle Aged , Models, Statistical , Odds Ratio , Risk , SoftwareABSTRACT
BACKGROUND: Colorectal cancer (CRC) results from the interaction between environmental exposures and genetic predisposition factors. AIMS: A case control study was designed and to investigate the genotype frequencies of P53Arg72Pro polymorphism in Malaysian CRC patients and healthy controls and to determine the associated risk of this polymorphism with CRC predisposition. METHODS: In this case-control study, peripheral blood samples of 202 sporadic CRC patients and 201 normal controls were collected, DNA extracted and genotyped using the polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) technique. RESULTS: Genotype analysis showed the frequency of homozygous variant (Pro/Pro) genotype (21%) to be significantly higher in cases compared to controls (13%), (p=0.013). On examining the association between variant genotypes and CRC risk, the Pro/Pro homozygous variant genotype showed significantly higher risk association with CRC susceptibility (OR: 2.047, CI: 1.063-4.044, p=0.033). When stratified according to age, we observed that, individuals aged above 50 years and carriers of pro/pro genotype had significantly higher risk with OR: 3.642, CI: 1.166-11.378, p=0.026. CONCLUSIONS: Our results suggest that the codon 72 SNP which results in amino acid substitution of Arginine to Proline in cell cycle regulatory gene P53, is associated with sporadic CRC risk and carriers of Pro/Pro genotype and more than 50 years old may have high susceptibility.