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| Naji, M. |
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| Motta, Antonella |
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| Mohamed, Tarek |
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| Ertürk, Emre |
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| Petrov, R. H. | Madrid |
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| Azam, Siraj |
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| Ali, M. A. |
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| Rančić, M. |
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| Azevedo, Nuno Monteiro |
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Singh, Navneet
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article
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
Abstract
<jats:title>Abstract</jats:title><jats:p>The present study investigated the relationship between <jats:italic>MLH1, MSH2, MSH3</jats:italic>, and <jats:italic>MSH6</jats:italic> 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 <jats:italic>MSH2 IVS1</jats:italic> + <jats:italic>9G</jats:italic> > <jats:italic>C</jats:italic> polymorphism variant type genotype reported a 1.4‐fold increased risk of anemia (AOR = 1.4; 95% CI = 0.98–1.99; <jats:italic>p</jats:italic> = 0.04) and decreased risk of developing gastrointestinal toxicity (diarrhea) (AOR = 0.53; 95% CI = 0.28–1.01; <jats:italic>p</jats:italic> = 0.04). Further, we also reported a 10‐fold increased risk of developing severe grade anorexia in combined genotype (<jats:italic>GC</jats:italic> + <jats:italic>CC</jats:italic>) (AOR = 9.18; 95% CI = 0.98–86.1; <jats:italic>p</jats:italic> = 0.05). For <jats:italic>MSH2 T</jats:italic> > <jats:italic>C/‐6</jats:italic> 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; <jats:italic>p</jats:italic> = 0.005) and neutropenia respectively (AOR = 2.23; 95% CI = 1.07–4.66; <jats:italic>p</jats:italic> = 0.03). For <jats:italic>MSH3 G</jats:italic> > <jats:italic>A</jats:italic> polymorphism, heterozygous (<jats:italic>GA</jats:italic>) and combined genotype (<jats:italic>GA</jats:italic> + <jats:italic>AA</jats:italic>) reported a 7‐fold and 6‐fold increased risk of developing anemia (AOR = 7.23; 95% CI = 1.51–34.6; <jats:italic>p</jats:italic> = 0.01, AOR = 6.39; 95% CI = 1.53–26.6; <jats:italic>p</jats:italic> = 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.</jats:p>