Association of MLH1-93G>A polymorphisms toward lung cancer susceptibility and its association with clinical outcome in North Indian patients treated with platinum-based chemotherapy

Abstract

Background: Lung cancer is one of the most prevalent and main causes of malignancy-related deaths worldwide, especially in developed countries. Epidemiological studies have demonstrated that individuals having alterations in a particular gene may have a high risk of developing certain types of cancer. Materials and Methods: In the present study, 500 Indian lung cancer patients and 500 healthy controls were enrolled. Polymerase chain reaction-restriction fragment length polymorphism method was used to identify the genotype of enrolled individuals and MedCalc statistical package was used for carrying out statistical analysis. Results: In this study, we found a reduced risk of developing adenocarcinoma in patients harboring variant (P = 0.0007) and combined type genotype (P = 0.008), whereas an increased risk for small-cell lung carcinoma (SCLC) development for those subject harboring GA genotypes (P = 0.03) was also observed. Further, heterozygous type and combined type genotype of heavy smokers for MLH1 polymorphism reported a 2-fold (P = 0.001) and 1.8-fold increased risk toward lung cancer development, respectively (P = 0.007). In case of females, the subjects harboring a variant allele have a significantly reduced risk for lung cancer development (P = 0.0001). For MLH1 polymorphism, reduced risk of developing tumor to T3 or T4 stage was observed (P = 0.04). Moreover, this is the first study reporting overall survival (OS) association for north Indian lung cancer patients with platinum-based doublet chemotherapy; for docetaxel, a three-fold increase in hazard ratio and corresponding low median standard survival time (8.4 months) for mutant and combined type genotype (P = 0.04) was observed. Conclusions: These results suggest that MLH1-93G>A polymorphism is involved in modulating the risk toward lung cancer. Our study also concluded a negative association of OS in patients undergoing carboplatin/cisplatin and docetaxel chemotherapy.