Title: DNA repair polymorphisms modify bladder cancer risk: a multi-factor analytic strategy.
Authors: Andrew, Angeline S; Karagas, Margaret R; Nelson, Heather H; Guarrera, Simonetta; Polidoro, Silvia; Gamberini, Sara; Sacerdote, Carlotta; Moore, Jason H; Kelsey, Karl T; Demidenko, Eugene; Vineis, Paolo; Matullo, Giuseppe
Published In Hum Hered, (2008)
Abstract: 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.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.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)).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.
PubMed ID: 17898541
MeSH Terms: Adult; Aged; DNA Repair/genetics*; Factor Analysis, Statistical; Humans; Informed Consent; Interviews as Topic; Italy; Middle Aged; Models, Genetic; New Hampshire/epidemiology; Polymorphism, Genetic*; Registries; Regression Analysis; Risk Factors; Urinary Bladder Neoplasms/epidemiology; Urinary Bladder Neoplasms/genetics*