The Association of Transporter Genes Polymorphisms and Lung Cancer Chemotherapy Response

Lung cancer is one of the most common cancers and is the leading cause of death worldwide. Platinum-based chemotherapy is the main treatment method in lung cancer patients. Our previous studies indicated that single nucleotide polymorphisms (SNPs) in some transporter genes played important role in platinum-based chemotherapy efficacy. The aim of this study was to investigate the association of SNPs in transporter genes and platinum-based chemotherapy efficacy. The main polymorphisms on transporters OCT2, LRP, AQP2, AQP9 and TMEM205 genes were genotyped in 338 lung cancer patients. The rs195854 in genotypic model, rs896412 in genotypic and recessive models for all subjects showed significant association with chemotherapy response. In stratification analysis, TMEM205 rs896412, OCT2 rs1869641 and rs195854, AQP9 rs1516400 and AQP2 rs7314734 showed significant relation to chemotherapy response. In conclusion, the genetic polymorphisms in OCT2, AQP2, AQP9 and TMEM205 may contribute to chemotherapy response in lung cancer patients.肺癌是全球范围内最常见的恶性肿瘤之一，亦是全球癌症相关死亡的首要原因。以铂类为基础的化疗是肺癌患者的主要治疗手段。我们前期的研究表明，部分转运蛋白基因中的单核苷酸多态性（Single Nucleotide Polymorphisms, SNPs）可对铂类化疗的疗效发挥重要作用。本研究旨在探讨转运蛋白基因中的SNPs与铂类化疗疗效之间的关联。本研究对338例肺癌患者体内转运蛋白基因OCT2、LRP、AQP2、AQP9及TMEM205的主要多态性位点进行了基因分型。在全部研究对象中，rs195854在基因型模型下、rs896412在基因型及隐性遗传模型下均与化疗应答存在显著关联。在分层分析中，TMEM205 rs896412、OCT2 rs1869641与rs195854、AQP9 rs1516400及AQP2 rs7314734均与化疗应答呈现显著相关性。综上，OCT2、AQP2、AQP9及TMEM205基因的遗传多态性可能与肺癌患者的化疗应答相关。