DNA repair gene polymorphisms, bulky DNA adducts in white blood cells and bladder cancer in a case-control study

✍ Scribed by Giuseppe Matullo; Simonetta Guarrera; Sonia Carturan; Marco Peluso; Christian Malaveille; Laura Davico; Alberto Piazza; Paolo Vineis

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: French
• Weight: 71 KB
• Volume: 92
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.1228

✦ Synopsis

Individuals differ widely in their ability to repair DNA damage, and DNA-repair deficiency may be involved in modulating cancer risk. In a case-control study of 124 bladder-cancer patients and 85 hospital controls (urological and non-urological), 3 DNA polymorphisms localized in 3 genes of different repair pathways (XRCC1-Arg399Gln, exon 10; XRCC3-Thr241Met, exon 7; XPD-Lys751Gln, exon 23) have been analyzed. Results were correlated with DNA damage measured as 32 P-post-labeling bulky DNA adducts in white blood cells from peripheral blood. Genotyping was performed by PCR-RFLP analysis, and allele frequencies in cases/controls were as follows: XRCC1-399Gln ‫؍‬ 0.34/0.39, XRCC3-241Met ‫؍‬ 0.48/0.35 and XPD-751Gln ‫؍‬ 0.42/0.42. Odds ratios (ORs) were significantly greater than 1 only for the XRCC3 (exon 7) variant, and they were consistent across the 2 control groups. XPD and XRCC1 appear to have no impact on the risk of bladder cancer. Indeed, the effect of XRCC3 was more evident in non-smokers [OR ‫؍‬ 4.8, 95% confidence interval (CI) 1.1-21.2]. XRCC3 apparently interacted with the N-acetyltransferase type 2 (NAT-2) genotype. The effect of XRCC3 was limited to the NAT-2 slow genotype (OR ‫؍‬ 3.4, 95% CI 1.5-7.9), suggesting that XRCC3 might be involved in a common repair pathway of bulky DNA adducts. In addition, the risk of having DNA adduct levels above the median was higher in NAT-2 slow acetylators, homozygotes for the XRCC3-241Met variant allele (OR ‫؍‬ 14.6, 95% CI 1.5-138). However, any discussion of interactions should be considered preliminary because of the small numbers involved. Our results suggest that bladder-cancer risk can be genetically modulated by XRCC3, which may repair DNA cross-link lesions produced by aromatic amines and other environmental chemicals.