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
Abstract
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.