HSD3B and Gene-Gene Interactions in a Pathway-Based Analysis of Genetic Susceptibility to Bladder Cancer
Year: 2012
Type: article
Study design: Observational Study
Abstract: Bladder cancer is the 4(th) most common cancer among men in the U.S. We analyzed variant genotypes hypothesized to modify major biological processes involved in bladder carcinogenesis, including hormone regulation, apoptosis, DNA repair, immune surveillance, metabolism, proliferation, and telomere maintenance. Logistic regression was used to assess the relationship between genetic variation affecting these processes and susceptibility in 563 genotyped urothelial cell carcinoma cases and 863 controls enrolled in a case-control study of incident bladder cancer conducted in New Hampshire, U.S. We evaluated gene-gene interactions using Multifactor Dimensionality Reduction (MDR) and Statistical Epistasis Network analysis. The 3'UTR flanking variant form of the hormone regulation gene HSD3B2 was associated with increased bladder cancer risk in the New Hampshire population (adjusted OR 1.85 95%CI 1.31-2.62). This finding was successfully replicated in the Texas Bladder Cancer Study with 957 controls, 497 cases (adjusted OR 3.66 95%CI 1.06-12.63). The effect of this prevalent SNP was stronger among males (OR 2.13 95%CI 1.40-3.25) than females (OR 1.56 95%CI 0.83-2.95), (SNP-gender interaction P = 0.048). We also identified a SNP-SNP interaction between T-cell activation related genes GATA3 and CD81 (interaction P = 0.0003). The fact that bladder cancer incidence is 3-4 times higher in males suggests the involvement of hormone levels. This biologic process-based analysis suggests candidate susceptibility markers and supports the theory that disrupted hormone regulation plays a role in bladder carcinogenesis.
Source: PLoS ONE
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
Funders: Dartmouth College, National Institutes of Health, University of Texas MD Anderson Cancer Center, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Environmental Health Sciences, U.S. National Library of Medicine, National Center for Research Resources
Awards: G1017177392, Bladder Cancer Prognostic Indicators, G1069150658, G1244673131, G1318433929, Comprehensive Assessment of Bladder Cancer Genetic Susceptibility, Molecular Epidemiology of Non-Melanoma Skin Cancer, G1697600358, G2272055386, G2298142304, G2299545052, G2526732409, G2535011669, Sources and Protracted Effects of Early Life Exposure to Arsenic and Mercury, G3073125414, G3084366702, G3118768502, G3131429433, G3329380511, G3330469080, G3940568135, SUPERFUND TOXIC SUBSTANCES--EXPOSURE AND DISEASE, Non-Melanoma Skin Cancer in New Hampshire, G4693112801, Harvard Chan School NIEHS Center for Environmental Health, Genome-Wide Association Analysis of Bladder Cancer, Machine Learning Prediction of Cancer Susceptibility, SPORE in Genitourinary Cancer, G6220864578, Quantitative Biology Research Institute, G676614207, DNA Repair and Bladder Cancer, G723185991, G7338041232, G734933981, Markers of Genetic Susceptibility to Bladder Cancer, Quantitative Biology Research Institute, G853500361, The Boston Collaborative Oral Cancer Study, G9000068125, G9000127527, G9000142562, G9000283202, Cancer Center Support Grant, Cancer Center Support Grant, Cellular and Molecular Mechanisms of Lung Disease, Telomere length, telomere maintenance gene polymorphisms, and bladder cancer risk
OpenAlex ID: W2086482109