Polymorphisms in solute carrier genes (SLC19A1, SLCO1B1, and SLCO1B3) predicts survival and toxicity in North Indian lung cancer patients undergoing platinum-based doublet chemotherapy.

Abstract

Solute Carrier (SLC) transporters are known mediators of drug disposition that facilitate the influx of substrates and various chemotherapeutic agents into cells. Polymorphisms in the SLC19A1, SLCO1B1, and SLCO1B3 gene influence the prognosis in the cancer patients, but little is known about their role in lung cancer in Asians. So, the current study aims to investigate the polymorphisms in SLC19A1, SLCO1B1, and SLCO1B3 genes in Northern Indian lung cancer patients. Patients with lung cancer who had a confirmed histology and cytology diagnosis were enrolled in the study. SLC polymorphisms were assessed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) for variations in SLC19A1 (G80 A), SLCO1B1 (A388 G, T521 C), and SLCO1B3 (A1683-5676 G). Our results showed that mutant genotype for SLC19A1 G80 A polymorphism had higher median survival time (MST) compared to wild genotype. ADCC patients with mutant genotype showed better survival compared to wild genotype for SLC19A1 G80 A. SCLC patients G80 A polymorphism showed increased survival in patients with mutant genotype (p=0.04). In SLCO1B3, A1683-5676 G patients carrying heterozygous alleles and administered with platinum and docetaxel showed inferior survival (p=0.006). In T521 C variant, patients with carrier genotype had reduced chances of developing anaemia (p=0.04). Patients with SLC19A1 and SLCO1B3 variants showed lower incidence of thrombocytopenia and nephrotoxicity. Our findings imply that Solute Carrier gene polymorphisms modulate the overall survival in lung cancer patients undergoing platin-based doublet chemotherapy, also these polymorphisms have a modifying impact on the associated adverse events/toxicity.