polymorphism genotypes, haplotypes, and diplotypes are associated with colorectal cancer predisposition and outcome in Tunisian population.

BACKGROUND AND AIM

As the presence of single nucleotide polymorphisms (SNPs) in the interleukin gene continues to be a major challenge in the development of effective therapies for digestive cancers, this case-control study was conducted to assess the possible influence of genotype, haplotype and diplotype for two SNPs (-1082A/G (rs1800896) and -592A/C (rs1800872)) located in the promoter region of gene on the incidence, severity and prognosis of colorectal cancer (CRC) in Tunisians.

METHODS

gene SNPs were analyzed in 130 CRC cases and 165 healthy subjects (HS) using PCR-SSP.

RESULTS

For the -1082A/G SNP, the comparison of genotype frequencies between cases and HS groups showed that the G allele significantly reduced CRC risk under the recessive model (GG vs. AA + AG: OR [95%CI] = 0.44 [0.21-0.93], p = 0.03). Conversely, a positive association was observed between the codominant model (AG vs. AA + GG) and high susceptibility (OR [95%CI] = 1.65 [1.02-2.63], p = 0.04). After stratification by disease site, the recessive model was also found to reduce susceptibility to colon cancer (OR [95%CI] = 0.18 [0.04-0.72], p = 0 0.01), while the homozygote model (AA vs. GG) was suggested as a risk factor (OR [95%CI] = 5.16 [1.31-23.26], p = 0.02). Furthermore, the codominant model (AG vs. AA + GG) doubled the risk of rectum cancer (OR [95%CI] = 1.98 [1.07-3.70], p = 0.03). For the -592A/C SNP, the codominant model (AC vs. AA + CC) has a protective effect against the development of CRC (OR [95%CI] = 0.59 [0.36-0.94], p = 0.03). The gene haplotype was not associated with CRC risk. A stratified analysis by disease site demonstrated that the presence of Hap3 (-1082G and -592C alleles) specifically reduced the risk of developing colon cancer (OR [95%CI] = 0.51 [0.32-0.80], p = 0.003). Moreover, homozygous Hap3/Hap3 diplotype significantly reduced susceptibility to CRC (OR [95%CI] = 0.35 [0.14-0.85], p = 0.02). Interestingly, this diplotype has not been identified in colon cancer patients. Kaplan-Meier analysis showed that the homozygous Hap2/Hap2 diplotype was significantly associated with decreased overall survival (Log-rank: p = 0.01). This association was also observed in the colon cancer subgroup (Log-rank: p = 0.001).

CONCLUSION

Our findings provide preliminary indications that the -1082A/G and -592/AC SNPs within the gene may exhibit significant associations with the pathogenesis and prognostic outcomes of CRC. However, further investigations are still warranted to validate and establish the veracity of our findings.