Sharma Parul, Singh Navneet, Sharma Siddharth
Department of Biotechnology, Thapar Institute of Engineering & Technology, Patiala, India.
Department of Pulmonary medicine, Post Graduate Institute of Medical Education & Research, Chandigarh, India.
J Clin Pharm Ther. 2022 Dec;47(12):2049-2067. doi: 10.1111/jcpt.13748. Epub 2022 Jul 27.
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 (G A), SLCO1B1 (A G, T C), and SLCO1B3 (A G).
Our results showed that mutant genotype for SLC19A1 G 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 G A. SCLC patients G A polymorphism showed increased survival in patients with mutant genotype (p = 0.04). In SLCO1B3, A G patients carrying heterozygous alleles and administered with platinum and docetaxel showed inferior survival (p = 0.006). In T 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.
溶质载体(SLC)转运蛋白是已知的药物处置介质,可促进底物和各种化疗药物进入细胞。SLC19A1、SLCO1B1和SLCO1B3基因的多态性会影响癌症患者的预后,但对于其在亚洲肺癌患者中的作用知之甚少。因此,本研究旨在调查印度北部肺癌患者中SLC19A1、SLCO1B1和SLCO1B3基因的多态性。
纳入经组织学和细胞学确诊的肺癌患者。通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)评估SLC基因多态性,以检测SLC19A1(G>A)、SLCO1B1(A>G、T>C)和SLCO1B3(A>G)的变异情况。
我们的结果显示,与野生型基因型相比,SLC19A1 G>A多态性的突变型基因型具有更长的中位生存时间(MST)。对于SLC19A1 G>A,携带突变型基因型的腺癌(ADCC)患者比野生型基因型患者具有更好的生存率。小细胞肺癌(SCLC)患者的G>A多态性显示,突变型基因型患者的生存率有所提高(p = 0.04)。在SLCO1B3中,携带杂合等位基因并接受铂类和多西他赛治疗的A>G患者生存率较低(p = 0.006)。在T>C变异中,携带基因型的患者发生贫血的几率降低(p = 0.04)。携带SLC19A1和SLCO1B3变异的患者血小板减少症和肾毒性的发生率较低。
我们的研究结果表明,溶质载体基因多态性可调节接受铂类双联化疗的肺癌患者的总生存期,并且这些多态性对相关不良事件/毒性具有调节作用。