Influence of Smoking on MLH1 gene Polymorphism: Insights into Colorectal Cancer Incidence

Background: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. The MutL Homolog 1 (MLH1) gene plays a critical role in DNA mismatch repair (MMR). Evidence suggests cigarette smoking increases CRC risk, potentially interacting with genetic factors. Materials and Methods: This case-control study involved 50 Iraqi CRC patients and 50 age- and gender-matched healthy controls. The PCR-RFLP technique was employed for genotyping the -93G/A (rs1800734) polymorphism. Statistical analysis included Chi-square, Fisher's Exact Test, and logistic regression adjusted for confounders. Hardy-Weinberg Equilibrium (HWE) was assessed in controls. Results: The frequency of the rs1800734 variant was significantly higher in CRC patients. The A-allele was more prevalent in the CRC group (41%) than controls (14%) (OR=4.27, 95%CI=1.7-14.53, p=0.003). The AA genotype was identified in 6 patients (all non-smokers) and was absent in controls and smoking subgroups. Logistic regression confirmed smoking exposure as an independent risk factor. Conclusion: The MLH1 promoter polymorphism -93G/A contributes to CRC susceptibility among Iraqi patients. Smoking remains a significant risk factor, potentially interacting with genetic predisposition. However, the absence of AA genotype in smokers suggests a complex gene-environment interaction requiring further investigation.