Objectives: 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.
© 2007 S. Karger AG, Basel
- DNA repair
- Bladder cancer
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Dr. Angeline S. Andrew
Dartmouth Medical School
Section of Biostatistics and Epidemiology , 7927 Rubin 860
One Medical Center Drive, Lebanon, NH 03756
Tel. +1 603 653 9019, Fax +1 603 653 9093, E-Mail Angeline.Andrew@dartmouth.edu
Received: March 11, 2007
Accepted after revision: June 8, 2007
Published online: September 26, 2007
Number of Print Pages : 14
Number of Figures : 3, Number of Tables : 5, Number of References : 53
Human Heredity (International Journal of Human and Medical Genetics)
Vol. 65, No. 2, Year 2008 (Cover Date: November 2007)
Journal Editor: Devoto, M. (Philadelphia, Pa.)
ISSN: 0001–5652 (print), 1423–0062 (Online)
For additional information: http://www.karger.com/HHE
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