Structural, functional analysis and association of MSH6 rs1800932, rs1042821 polymorphisms with clinical outcome in North Indian lung cancer patients treated with platinum-based doublet chemotherapy.

Abstract

In this study, we have done structural and functional analysis of rs1800932 rs1042821 polymorphisms and tried to estimate any association of these polymorphisms with clinical outcomes in north Indian lung cancer patients. Genotyping of 500 lung cancer patients was completed utilizing PCR-RFLP (Polymerase chain reaction- Restriction fragment length polymorphism). MedCalc statistical software was used to calculate adjusted and unadjusted odds ratios. Various computational tools like SIFT PROVEAN are used for functional analysis. Structural analysis was completed via MODELLER and CHIMERA. In our study, patients suffering from small cell lung cancer (SCLC) and harboring heterozygous genotype (AG) for MSH6 (rs1800932) polymorphism have reported a significant increase in median survival time (MST) (20.6vs. 7.6 months, p=0.03). Furthermore, for MSH6 rs1042821 polymorphism, patients undergoing docetaxel and carbo/cisplatin combination chemotherapeutic regimen and carrying heterogeneous genotype (CT) reported a significant increase in MST (16.6vs.8.36 months, p=0.03) and a corresponding decrease in hazard ratio 0.42 (95% CI= 0.18-1.03). Structural and Functional analysis of rs1042821 polymorphism revealed that it is present in the non-coding region of MSH6 protein and is significantly associated with increased overall survival. These results suggest that MSH6 rs1800932 rs1042821 polymorphisms are involved in increasing the overall survival of lung cancer patients, further confirmed by computational analysis.