Oligogenic segregation analysis of hereditary prostate cancer pedigrees: Evidence for multiple loci affecting age at onset

• Published in: International journal of cancer Vol. 105; no. 5; pp. 630 - 635
• Main Authors: Conlon, Erin M., Goode, Ellen L., Gibbs, Mark, Stanford, Janet L., Badzioch, Michael, Janer, Marta, Kolb, Suzanne, Hood, Lee, Ostrander, Elain A., Jarvik, Gail P., Wijsman, Ellen M.
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 10.07.2003; Wiley-Liss
• Subjects: Adenocarcinoma - diagnosis; Adenocarcinoma - epidemiology; Adenocarcinoma - genetics; Adult; Age of Onset; Aged; Antigens, Neoplasm - blood; ascertainment; Bayes Theorem; Bayesian; Biological and medical sciences; Biomarkers, Tumor - blood; Brain Neoplasms - epidemiology; Brain Neoplasms - genetics; Chromosome Segregation; Cohort Studies; genetic heterogeneity; Genetic Predisposition to Disease; Genotype; Humans; Male; Markov chain Monte Carlo; Markov Chains; Medical sciences; Middle Aged; Neoplastic Syndromes, Hereditary - epidemiology; Neoplastic Syndromes, Hereditary - genetics; Nephrology. Urinary tract diseases; Neuroectodermal Tumors, Primitive - epidemiology; Neuroectodermal Tumors, Primitive - genetics; Pedigree; Prostate-Specific Antigen - blood; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - epidemiology; Prostatic Neoplasms - genetics; Quantitative Trait Loci; quantitative traits; Tumors of the urinary system; United States - epidemiology; Urinary tract. Prostate gland; United States; Bayes estimation; Human; Urinary system disease; Prostate disease; Malignant tumor; Hereditary; Genetic disease; Quantitative trait loci; Statistical method; Segregation analysis; Heterogeneity; MCMC algorithm; Age of onset; Genetics; Male genital diseases; Prostate
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.11128

Previous studies have suggested strong evidence for a hereditary component to prostate cancer (PC) susceptibility. Here, we analyze 3,796 individuals in 263 PC families recruited as part of the ongoing Prostate Cancer Genetic Research Study (PROGRESS). We use Markov chain Monte Carlo (MCMC) oligogenic segregation analysis to estimate the number of quantitative trait loci (QTLs) and their contribution to the variance in age at onset of hereditary PC (HPC). We estimate 2 covariate effects: diagnosis of PC before and after prostate‐specific antigen (PSA) test availability, and presence/absence of at least 1 blood relative with primary neuroepithelial brain cancer (BC). We find evidence that 2 to 3 QTLs contribute to the variance in age at onset of HPC. The 2 QTLs with the largest contribution to the total variance are both effectively dominant loci. We find that the covariate for diagnosis before and after PSA test availability is important. Our findings for the number of QTLs contributing to HPC and the variance contribution of these QTLs will be instructive in mapping and identifying these genes. © 2003 Wiley‐Liss, Inc.