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Background

Genetic polymorphism within the P1 isoenzyme of the Glutathione-S-Transferase (GST) family is found to modulate and alter the enzyme activity of GSTP1 protein and thus may result in a change of sensitivity to platinum-based chemotherapy. We investigated the relationship between GSTP1 Ile105Val polymorphisms and overall survival, treatment response, and for both hematological and non-hematological toxicity of advanced North Indian lung cancer patients undergoing platinum-based double chemotherapy.

Methods

The polymorphism of GSTP1 Ile105Val in North Indian lung cancer patients was assessed by polymerase chain reaction-restriction fragment length polymorphism. A total of 682 lung cancer patients were enrolled in the study, and it was observed that patients who were carrying both the mutant alleles (Val/Val) for the GSTP1 polymorphism showed a higher trend of median survival time (MST) as compared to the patients bearing the wild type of genotype (Ile/Ile) (MST = 8.30 vs. 7.47, p = 0.56). Based on toxicity profiling, we observed that lung cancer patients with the mutant genotype of GSTP1 (Val/Val) had an increased risk of leukopenia (OR = 2.41; 95% CI = 1.39-4.18, p = 0.001) as compared to subjects carrying both copies of the wild alleles (Ile/Ile). Our data suggested that patients with heterozygous genotype (Ile/Val) had a 2.14-fold increased risk of developing severe anemia (OR = 2.14, 95% CI = 0.97-4.62, p = 0.03). Our data also showed that in small cell lung carcinoma (SCLC) patients' polymorphism of GSTP1 was associated with thrombocytopenia (χ2 test = 7.32, p = 0.02).

Conclusions

Our results suggest that GSTP1 Ile105Val polymorphism could be a predictive biomarker for hematological toxicity, like leukopenia and anemia, but not thrombocytopenia or neutropenia."xsd:string
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http://purl.uniprot.org/citations/34780261http://purl.uniprot.org/core/author"Sharma S."xsd:string
http://purl.uniprot.org/citations/34780261http://purl.uniprot.org/core/author"Singh N."xsd:string
http://purl.uniprot.org/citations/34780261http://purl.uniprot.org/core/author"Walia H.K."xsd:string
http://purl.uniprot.org/citations/34780261http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/34780261http://purl.uniprot.org/core/name"Hum Exp Toxicol"xsd:string
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http://purl.uniprot.org/citations/34780261http://purl.uniprot.org/core/title"GSTP1 Ile105Val polymorphism among North Indian lung cancer patients treated using monotherapy and poly-pharmacy."xsd:string
http://purl.uniprot.org/citations/34780261http://purl.uniprot.org/core/volume"40"xsd:string
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