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 ) andSLCO1B3 (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 G80Apolymorphism 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.
Keywords: Lung cancer, SLC transporter, survival, platinum-based chemotherapy, polymorphism, Toxicity