Association between DNA Repair Gene Polymorphisms and p53 Alterations in Japanese Patients with Muscle-Invasive Bladder Cancer
Shigeru Sakano Hiroaki Matsumoto Yoshiaki Yamamoto Yoshihisa Kawai Satoshi Eguchi Chietaka Ohmi Hideyasu Matsuyama Katsusuke NaitoSakano S. · Matsumoto H. · Yamamoto Y. · Kawai Y. · Eguchi S. · Ohmi C. · Matsuyama H. · Naito K.
Department of Urology, Yamaguchi University School of Medicine, Ube, Japan
Objective: DNA repair enzymes play a vital role in protecting the genome from carcinogens, several of which can cause mutations in the TP53 gene in bladder cancer. Some single nucleotide polymorphisms (SNPs) in DNA repair genes reportedly modulate the repair capacity. This study aimed to clarify the effect of these functional SNPs on the alteration of p53 in muscle-invasive bladder cancer. Methods: We investigated the association between SNPs in xeroderma pigmentosum complementation groups C (XPC), D and G and X-ray repair cross-complementing group 1 and 3 genes, and p53 expression and allelic imbalance at the TP53 locus in Japanese patients with muscle-invasive bladder cancer. p53 expression and the allelic imbalance were evaluated using immunohistochemistry and a microsatellite marker, respectively. Results: Positive p53 expression was significantly less frequent in patients with the CC genotype of the XPC gene than in those with the AA or AC genotype (p = 0.0005). C alleles of the XPC gene were also less frequent in patients with positive p53 expression (p = 0.01). Conclusion: Our results suggested that the XPC polymorphism might affect p53 alteration and the molecular pathway defined by the p53 alteration in the development of muscle-invasive bladder cancer.
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