title: Genetic polymorphisms in 85 DNA repair genes and bladder cancer risk.
abstract: Several defense mechanisms have been developed and maintained during the evolution to protect human cells against damage produced from exogenous or endogenous sources. We examined the associations between bladder cancer and a panel of 652 polymorphisms from 85 genes involved in maintenance of genetic stability [base excision repair, nucleotide excision repair, double-strand break repair (DSBR) and mismatch repair, as well as DNA synthesis and cell cycle regulation pathways] in 201 incident bladder cancer cases and 326 hospital controls. Score statistics were used to test differences in haplotype frequencies between cases and controls in an unconditional logistic regression model. To account for multiple testing, we associated to each P-value the expected proportion of false discoveries (q-value). Haplotype analysis revealed significant associations (P < 0.01) between bladder cancer and two genes (POLB and FANCA) with an associated q-value of 24%. A permutation test was also used to determine whether, in each pathway analyzed, there are more variants whose allelic frequencies are different between cases and controls as compared with what would be expected by chance. Differences were found for cell cycle regulation (P = 0.02) and to a lesser extent for DSBR (P = 0.05) pathways. These results hint to a few potential candidate genes; however, our study was limited by the small sample size and therefore low statistical power to detect associations. It is anticipated that genome-wide association studies will open new perspectives for interpretation of the results of extensive candidate gene studies such as ours.
authors.affiliation: Department of Biostatistics and Epidemiology, Institut Gustave Roussy, Villejuif 94805, France.
authors.forename: Stefan
authors.initials: S
authors.lastname: Michiels
authors.forename: Agnès
authors.initials: A
authors.lastname: Laplanche
authors.forename: Thomas
authors.initials: T
authors.lastname: Boulet
authors.forename: Philippe
authors.initials: P
authors.lastname: Dessen
authors.forename: Bertrand
authors.initials: B
authors.lastname: Guillonneau
authors.forename: Arnaud
authors.initials: A
authors.lastname: Méjean
authors.forename: François
authors.initials: F
authors.lastname: Desgrandchamps
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.forename: Alain
authors.initials: A
authors.lastname: Sarasin
authors.forename: Simone
authors.initials: S
authors.lastname: Benhamou
mesh_terms: D000328:Adult; D000368:Aged; D002453:Cell Cycle / Q000235:genetics; D019951:DNA Polymerase beta / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics; D052217:Fanconi Anemia Complementation Group A Protein / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010297:Paris; D011110:Polymorphism, Genetic; D012016:Reference Values; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D044465:White People / Q000235:genetics
chemical_list: C498471:FANCA protein, human; D052217:Fanconi Anemia Complementation Group A Protein; D019951:DNA Polymerase beta