rs1625649

This candidate gene association study examined 16 DNA repair gene polymorphisms in 94 patients with metastatic colorectal cancer treated with oxaliplatin-based chemotherapy. The MGMT -535G>T polymorphism (rs1625649) was found to be significantly associated with progression-free survival (PFS) (p=0.076 in univariate analysis), with TT genotype showing improved prognosis compared to GG/GT genotypes (HR=3.137, p=0.005 in multivariate analysis). Several other polymorphisms in DNA repair genes were evaluated for associations with chemotherapy response and survival outcomes.

This haplotype-based association study of 500 lung cancer cases and 517 controls examined genetic variation in the MGMT gene (a DNA repair protein) in southeastern Chinese population. Using multifactor dimensionality reduction (MDR) analysis, researchers identified significant gene-environment interactions between MGMT haplotypes (particularly block 5 diplotypes and preblock SNP rs1625649:C>A) and smoking status. Subjects carrying the combined risk genetic and smoking stratum had a 4.10-fold increased lung cancer risk (OR=4.10, 95% CI=3.12-5.37, P=2.09×10^-24), suggesting MGMT variants modulate smoking-related lung cancer susceptibility.