The Associations Between The Klotho Gene G-395A Polymorphisms And The Risk Of Bladder Cancer

Background:Bladder cancer is the first common urothelial carcinoma in China. Almost all patients with distant metastatic bladder cancer die within1to2years despite treatment with the most effective regimens available. Bladder cancer is typically treated with various combinations of systemic chemotherapy. Standard treatment for bladder cancer has been methotrexate, vinblastine, doxorubicin and cisplatin. Gemcitabine was found to have efficacy similar to that of M-VAC but with lower toxicity. It is needed to improve the results of current bladder cancer treatment nontoxic agents. Then the efficacy of cytotoxic chemotherapy for bladder cancer might be augmented. Oxaliplatin is the group of agents that hold promise. The individual inhibitory effects of oxaliplatin is significantulu enhaced, especially the substances are used in combination. We are interested in these biological effects of gemcitabine and oxaliplatin. Its potential role against bladder cancer was evaluated in our research.Objects:Bladder cancer signaling pathways, ncluding the adaptor protein encoded by the KLOTHO genes, play a central role in the development of Bladder cancer. Recently, the KLOTHO genes variants have been descfbed association with susceptibility to infiammatofy diseases. The aim ofthis study was to investigate the association between Klotho gene polymorphisms and the risk of bladder cancer..Methods:A case control collection from162healthy subjects,180bladder cancer patients were included eight tag single nucleotide polymorphisms (SNPs) of the Klotho gene and two additional SNPs that have previously showed association with susceptibility to other diseases were genotyped by direct sequencing. The differences of allele, genotype and haplotype frequencies were evaluated between two groupsResults:The minor allele frequencies of both were significantly increased in Bladder cancer patients compared with both healthy subjects and Bladder cancer patients. Haplotype consisting of these two associated SNPs strerlgmened the association with Bladder cancer susceptibility. The frequency of haplotype AG in the Bladder cancer samples was significantly higher than that in the healthy subjects. Carders of the haplotype AG (G-395A)had a lower risk for Bladder cancer compared with healthy control group. These associations remained significant after adiuatment for covariates in multiple logistic regression analysis andformultiple comparisonsConclusions:These results indicated that genetic variants in the KLOTHO gene might be associated with susceptibility to older bladder cancer patients (≥60years) in the study population However, the association needs to be replicated in independent studies.