Genetic polymorphisms in the mismatch repair pathway (MMR) genes contribute to hematological and gastrointestinal toxicity in North Indian lung cancer patients treated with platinum-based chemotherapy.

The present study investigated the relationship between MLH1, MSH2, MSH3, and MSH6 polymorphisms and toxicity due to platinum-based doublet chemotherapy for North Indian lung cancer patients. Polymerase chain reaction-restriction fragment length polymorphism technique was used to assess the polymorphism. For MSH2 IVS1 + 9G > C polymorphism variant type genotype reported a 1.4-fold increased risk of anemia (AOR = 1.4; 95% CI = 0.98-1.99; p = 0.04) and decreased risk of developing gastrointestinal toxicity (diarrhea) (AOR = 0.53; 95% CI = 0.28-1.01; p = 0.04). Further, we also reported a 10-fold increased risk of developing severe grade anorexia in combined genotype (GC + CC) (AOR = 9.18; 95% CI = 0.98-86.1; p = 0.05). For MSH2 T > C/-6 polymorphism, variant type reported a 3-fold and 2-fold increased risk of developing severe grade leukopenia (AOR = 3.37; 95% CI = 1.44-7.88; p = 0.005) and neutropenia respectively (AOR = 2.23; 95% CI = 1.07-4.66; p = 0.03). For MSH3 G > A polymorphism, heterozygous (GA) and combined genotype (GA + AA) reported a 7-fold and 6-fold increased risk of developing anemia (AOR = 7.23; 95% CI = 1.51-34.6; p = 0.01, AOR = 6.39; 95% CI = 1.53-26.6; p = 0.01). Our results suggest that polymorphisms in DNA mismatch repair genes are associated with hematological, and gastrointestinal toxicities and might be considered a predictor for pretreatment evaluation in lung cancer patients.