Genetic polymorphisms in the DNA repair genes XPD and XRCC1, p53 gene mutations and bladder cancer risk

Abstract

Abstract. Previous studies have suggested that certain genetic polymorphisms, specifically the Xeroderma pigmentosum group D (XPD) gene codon 751 and the X-ray repair crosscomplementing group 1 (XRCC1) gene codon 399 polymorphisms, were associated with an increased risk of lung cancer, and, in some studies, with a greater risk for mutations in the p53 tumor suppressor gene in lung tumors. To evaluate whether these gene polymorphisms may be associated with an increased risk for bladder cancer or in association with p53 mutation status in bladder tumors, we screened for polymorphisms at XPD codons 751 and XRCC1 codon 399 in DNA isolated from blood of 194 bladder cancer patients and 313 healthy controls and for mutations in exons 4 to 8 of the p53 gene in bladder tumor DNA from 174 bladder cancer patients. There was a significantly higher prevalence of the XPD 751 Gln allele among the bladder cancer group, compared with the control group. No association was found between bladder cancer risk and the XRCC1 399 polymorphism. p53 mutations were found in 20.1% (35/174) patients. There was no difference in p53 mutation status among individuals with different genotypes. These results suggest that individuals who have the XPD 751 Gln allele may be at an increased risk for bladder cancer, although this may not lead to an increased risk for mutations in the p53 gene.

The effect of tobacco, XPC, ERCC2 and ERCC5 genetic variants in bladder cancer development

“…Our observation of no association of the XPD Lys751Gln genotypes with the risk of Bladder cancer is compatible with the findings from Shen et al [ 13 ] and Gangwar et al [ 30 ] who reported no association of the ERCC2 codon 751 polymorphism with bladder cancer risk. However, Gao et al[ 16 ] and Li et al [ 17 ] suggest that individuals who have the ERCC2 751Gln allele may be at an increased risk for bladder cancer. Authors explain this association by the fact that ERCC2 gene mutations can diminish the activity of TFIIH complexes giving rise to repair defects, transcription defects, and abnormal responses to apoptosis [ 31 ].…”

Genetic Polymorphisms Involved in Bladder Cancer: A Global Review

“…In X-ray repair cross-complementing protein 1 (XRCC1), rs1799782 and rs25489 are widely associated with an increased risk for BC, especially in Asian and Indian populations [146][147][148][149][150][151][152]. Rs915927 in the same gene increases tumor susceptibility in the Italian population [153] while rs25487 gave contradictory results in different studies [147][148][149][154][155][156][157][158][159]. Rs3218373, rs3218536, and rs6464268 in XRCC2 present a protective effect towards BC in the Italian population [160].…”

XRCC1 and XPD Polymorphisms: Clinical Outcomes and Risk of Prostate Cancer in Bangladeshi Population

“…The XPD protein, an essential subunit of the transcription factor IIH (TFIIH) complex, unwinds DNA in damaged regions [22]. An XPD variant at position 751 in exon 23 (at position 35931 on exon 23, base A to C, rs13181) causing a lysine-to-glutamine transition has been associated with non-small cell lung cancer [23], breast cancer [24], bladder cancer [25], and colorectal cancer [26]. However, several studies failed to identify an increased PCa risk with XPD Lys751Gln polymorphism, namely in the Indian population [27], the Taiwanese population [28], and the South Australian population [29].…”