title: DNA repair polymorphisms modify bladder cancer risk: a multi-factor analytic strategy.
abstract: OBJECTIVE
  A number of common non-synonymous single nucleotide polymorphisms (SNPs) in DNA repair genes have been reported to modify bladder cancer risk. These include: APE1-Asn148Gln, XRCC1-Arg399Gln and XRCC1-Arg194Trp in the BER pathway, XPD-Gln751Lys in the NER pathway and XRCC3-Thr241Met in the DSB repair pathway.
  
  
  METHODS
  To examine the independent and interacting effects of these SNPs in a large study group, we analyzed these genotypes in 1,029 cases and 1,281 controls enrolled in two case-control studies of incident bladder cancer, one conducted in New Hampshire, USA and the other in Turin, Italy.
  
  
  RESULTS
  The odds ratio among current smokers with the variant XRCC3-241 (TT) genotype was 1.7 (95% CI 1.0-2.7) compared to wild-type. We evaluated gene-environment and gene-gene interactions using four analytic approaches: logistic regression, Multifactor Dimensionality Reduction (MDR), hierarchical interaction graphs, classification and regression trees (CART), and logic regression analyses. All five methods supported a gene-gene interaction between XRCC1-399/XRCC3-241 (p = 0.001) (adjusted OR for XRCC1-399 GG, XRCC3-241 TT vs. wild-type 2.0 (95% CI 1.4-3.0)). Three methods predicted an interaction between XRCC1-399/XPD-751 (p = 0.008) (adjusted OR for XRCC1-399 GA or AA, XRCC3-241 AA vs. wild-type 1.4 (95% CI 1.1-2.0)).
  
  
  CONCLUSIONS
  These results support the hypothesis that common polymorphisms in DNA repair genes modify bladder cancer risk and highlight the value of using multiple complementary analytic approaches to identify multi-factor interactions.
authors: Department of Community and Family Medicine, Section of Biostatistics and Epidemiology, Dartmouth Medical School, Lebanon, NH 03756, USA. Angeline.Andrew@dartmouth.edu
authors: Angeline S
authors: AS
authors: Andrew
authors: Margaret R
authors: MR
authors: Karagas
authors: Heather H
authors: HH
authors: Nelson
authors: Simonetta
authors: S
authors: Guarrera
authors: Silvia
authors: S
authors: Polidoro
authors: Sara
authors: S
authors: Gamberini
authors: Carlotta
authors: C
authors: Sacerdote
authors: Jason H
authors: JH
authors: Moore
authors: Karl T
authors: KT
authors: Kelsey
authors: Eugene
authors: E
authors: Demidenko
authors: Paolo
authors: P
authors: Vineis
authors: Giuseppe
authors: G
authors: Matullo
mesh_terms: D000328:Adult; D000368:Aged; D004260:DNA Repair / Q000235:genetics*; D005163:Factor Analysis, Statistical; D006801:Humans; D007258:Informed Consent; D007407:Interviews as Topic; D007558:Italy; D008875:Middle Aged; D008957:Models, Genetic; D009513:New Hampshire / Q000453:epidemiology; D011110:Polymorphism, Genetic; D012042:Registries; D012044:Regression Analysis; D012307:Risk Factors; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology / Q000235:genetics*