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Association between genetic polymorphisms in SLC19A1, SLCO1B1 and SLCO1B3 genes predicts survival and toxicity in North Indian lung cancer patients undergoing platinum-based doublet chemotherapy
  • Parul Sharma,
  • Navneet Singh,
  • Siddharth Sharma
Parul Sharma
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Navneet Singh
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Siddharth Sharma
Thapar Institute of Engineering and Technology

Corresponding Author:[email protected]

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Abstract Aims: SLC transporters are expressed in lungs and are essential membrane proteins responsible for the transport of wide range of chemotherapeutic drugs. Polymorphisms in SLC19A1, SLCO1B1, and SLCO1B3 gene in North Indian lung cancer patients are investigated. Methods: A total of 610 lung cancer patients undergoing platinum-based chemotherapy were recruited in the study. Polymorphisms of SLC19A1 (G80A), SLCO1B1 (A388G, T521C) and SLCO1B3 (A1683-5676G) in North Indian lung cancer patients were assessed and statistical analysis were carried out. Results: Our data revealed that patients harboring mutant genotype (AA) for SLC19A1 G80A polymorphism had higher MST as compared patients with wild type (GG) genotype (MST=9.33 versus 8.23). ADCC patients with mutant genotype (AA) showed better survival outcomes for SLC19A1 G80A (MST=9.4 versus 8.8, HR=0.6; p=0.04). In SCLC, SLC19A1 G80A polymorphism revealed increased survival in the patients harboring mutant genotype (AA) (MST=9.6 months versus 7.6 months, p=0.04). For SLCO1B3 polymorphism, patients administered with carboplatin/cisplatin and docetaxel showed inferior survival outcomes in subjects carrying heterozygous alleles (AG) (MST=2.9 months versus 9.6 months, p=0.006, HR=14.01). For anemia, SLCO1B1 T521C showed that patients with heterozygous genotype (TC) had a reduced risk of developing anemia (OR=0.44, 95% CI=0.20-0.96; p=0.04). Patients with SLCO1B1 A388G polymorphism harboring AG alleles was associated with a lower incidence of thrombocytopenia (OR=0.41, 95% CI=0.20-0.82; p=0.01). Patients with heterozygous (AG) genotype (OR=0.35, 95% CI=0.17-0.72; p=0.002) for A1683-5676G polymorphism showed lower incidence of nephrotoxicity. Conclusion: Genotyping of SLC polymorphism is crucial for predicting survival and toxicity in lung cancer patients undergoing platinum-based chemotherapy.