Bladder Cancer Predisposition: A Multigenic Approach to DNA-Repair and Cell-Cycle–Control Genes

The candidate-gene approach in association studies of polygenic diseases has often yielded conflicting results. In this hospital-based case-control study with 696 white patients newly diagnosed with bladder cancer and 629 unaffected white controls, we applied a multigenic approach to examine the ass...

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Bibliographic Details
Published in:American journal of human genetics 2006-03, Vol.78 (3), p.464-479
Main Authors: Wu, Xifeng, Gu, Jian, Grossman, H. Barton, Amos, Christopher I., Etzel, Carol, Huang, Maosheng, Zhang, Qing, Millikan, Randal E., Lerner, Seth, Dinney, Colin P., Spitz, Margaret R.
Format: Article
Language:English
Subjects:
Aged
Biological and medical sciences
Bladder cancer
Cell culture
Cell Cycle - genetics
Cigarettes
Defense mechanisms
DNA repair
DNA Repair - genetics
Effects
Female
Free radicals
Gene Frequency
General aspects. Genetic counseling
Genes
Genetic Predisposition to Disease
Humans
Male
Medical genetics
Medical sciences
Middle Aged
Molecular Epidemiology
Nephrology. Urinary tract diseases
Polymorphism, Single Nucleotide
Risk Factors
Sample size
Smoking
Statistical analysis
Statistical methods
Tobacco smoke
Tumors of the urinary system
Urinary Bladder Neoplasms - epidemiology
Urinary Bladder Neoplasms - genetics
Urinary system involvement in other diseases. Miscellaneous
Urinary tract. Prostate gland
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Summary:The candidate-gene approach in association studies of polygenic diseases has often yielded conflicting results. In this hospital-based case-control study with 696 white patients newly diagnosed with bladder cancer and 629 unaffected white controls, we applied a multigenic approach to examine the associations with bladder cancer risk of a comprehensive panel of 44 selected polymorphisms in two pathways, DNA repair and cell-cycle control, and to evaluate higher-order gene-gene interactions, using classification and regression tree (CART) analysis. Individually, only XPD Asp312Asn, RAG1 Lys820Arg, and a p53 intronic SNP exhibited statistically significant main effects. However, we found a significant gene-dosage effect for increasing numbers of potential high-risk alleles in DNA-repair and cell-cycle pathways separately and combined. For the nucleotide-excision repair pathway, compared with the referent group (fewer than four adverse alleles), individuals with four (odds ratio [OR] = 1.52, 95% CI 1.05–2.20), five to six (OR = 1.81, 95% CI 1.31–2.50), and seven or more adverse alleles (OR = 2.50, 95% CI 1.69–3.70) had increasingly elevated risks of bladder cancer ( P for trend
ISSN:0002-9297
1537-6605
DOI:10.1086/500848