Abstract
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.
Highlights
Lung cancer is one of the most common cancers and is the leading cause of death worldwide [1]
We investigate the association of 5 transporter genes (OCT2, AQP2, AQP9, MVP and Transmembrane protein 205 (TMEM205)) single nucleotide polymorphisms (SNPs) with
Our results showed that SNPs rs195854 (OCT2) and rs186941 (OCT2), rs7314734 (AQP2), rs1516400 (AQP9), and rs896412 (TMEM205) might be related with chemotherapy response in lung cancer patients
Summary
Lung cancer is one of the most common cancers and is the leading cause of death worldwide [1]. The chemotherapy resistance has several mechanisms, including reduced platinum compounds accumulation (decrease intake or increase efflux by transporters), detoxification, or increased level of DNA damage repair and so on [3,5]. Several transporters contribute to platinum accumulation in the cancer cells. Transmembrane protein 205 (TMEM205) may decrease the accumulation of platinum compound by increasing efflux [5]. The organic cation transporter 2 (OCT2), encoded by SLC22A2 gene, had a potential role of increasing platinum uptake and sensitivity [10,11,12]. Resistance-related protein (MVP/LRP) can up-regulate sensitivity by increasing cellular cisplatin accumulation and/or by decreasing cisplatin efflux from nuclei in ovarian cancer cells [13]. To sum up, increasing the expression of AQP2, AQP9, OCT2 and MVP/LRP or decreasing the expression of TMEM205 might lead to platinum sensitivity
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