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Table of Contents
Vol. 65, No. 2, 2008
Issue release date: November 2007
Section title: Original Paper
Free Access
Hum Hered 2008;65:105–118

DNA Repair Polymorphisms Modify Bladder Cancer Risk: A Multi-factor Analytic Strategy

Andrew A.S.a · Karagas M.R.a · Nelson H.H.e · Guarrera S.c · Polidoro S.c · Gamberini S.c · Sacerdote C.c · Moore J.H.b · Kelsey K.T.f · Demidenko E.a · Vineis P.c, g · Matullo G.c, d
aDepartment of Community and Family Medicine, Section of Biostatistics and Epidemiology, and bDepartment of Genetics, Computational Genetics Laboratory, Dartmouth Medical School, Lebanon, N.H., USA; cI.S.I Foundation and dDepartment of Genetics, Biology and Biochemistry, Torino, Italy; Departments of eEnvironmental Health and fGenetics and Complex Diseases, Harvard School of Public Health, Boston, Mass., gImperial College London, St Mary’s Campus, London, UK
email Corresponding Author

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

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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

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: March 11, 2007
Accepted: June 08, 2007
Published online: September 26, 2007
Issue release date: November 2007

Number of Print Pages: 14
Number of Figures: 3
Number of Tables: 5

ISSN: 0001-5652 (Print)
eISSN: 1423-0062 (Online)

For additional information: http://www.karger.com/HHE

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