Year: 2007
Type: article
Study design: Observational Study
Abstract: 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.
Source: Human Heredity
DOI: 10.1159/000108942
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Awards: G1017177392, Bladder Cancer Prognostic Indicators, G1069150658, G1318433929, Molecular Epidemiology of Non-Melanoma Skin Cancer, G2298142304, G2299545052, G2526732409, Sources and Protracted Effects of Early Life Exposure to Arsenic and Mercury, G3084366702, G3118768502, SUPERFUND TOXIC SUBSTANCES--EXPOSURE AND DISEASE, Non-Melanoma Skin Cancer in New Hampshire, Harvard Chan School NIEHS Center for Environmental Health, G6220864578, DNA Repair and Bladder Cancer, G723185991, G9000127527, G9000283202, Cancer Center Support Grant, Cellular and Molecular Mechanisms of Lung Disease
OpenAlex ID: W2037827636