Association between DNA repair gene polymorphisms and p53 alterations in Japanese patients with muscle-invasive bladder cancer.
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).


CONCLUSIONS
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.
Sakano
Shigeru
S
Department of Urology, Yamaguchi University School of Medicine, Ube, Japan.
Matsumoto
Hiroaki
H
Yamamoto
Yoshiaki
Y
Kawai
Yoshihisa
Y
Eguchi
Satoshi
S
Ohmi
Chietaka
C
Matsuyama
Hideyasu
H
Naito
Katsusuke
K
D000368:Aged; D000369:Aged, 80 and over; D022981:Allelic Imbalance; D044466:Asian People / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D004720:Endonucleases / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009130:Muscle, Smooth / Q000473:pathology*; D009154:Mutation; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics; D000099250:DNA Excision Repair Protein ERCC-5
D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein; D000099250:DNA Excision Repair Protein ERCC-5; C495901:TP53 protein, human; C110901:X-ray repair cross complementing protein 3; C086984:XPC protein, human; C497292:ERCC2 protein, human