Genome-wide linkage analysis for aggressive prostate cancer in Utah high-risk pedigrees

• Published in: The Prostate Vol. 67; no. 6; pp. 605 - 613
• Main Authors: Christensen, G.B., Camp, N.J., Farnham, J.M., Cannon-Albright, L.A.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.05.2007; Wiley-Liss
• Subjects: Aged; aggressive; Biological and medical sciences; DNA, Neoplasm - analysis; Genetic Linkage; Genetic Predisposition to Disease; Genome, Human; Genotype; Gynecology. Andrology. Obstetrics; Humans; Lod Score; Male; Male genital diseases; Medical sciences; Microsatellite Repeats; Middle Aged; Nephrology. Urinary tract diseases; Pedigree; prostate cancer; Prostatic Neoplasms - epidemiology; Prostatic Neoplasms - genetics; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Utah - epidemiology; United States; North America; Utah; America; Andrology; High risk; Nephrology; Urinary system disease; Prostate disease; Family study; Gynecology; Malignant tumor; Pedigree; Genetic linkage; Genetics; aggressive; Genome; Male genital diseases; Prostate cancer; High malignancy
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.20554

BACKGROUND It has been proposed that studying alternative phenotypes, such as tumor aggressiveness, may be a solution for overcoming the apparent heterogeneity that has hindered the identification of prostate cancer (PC) genes. We present the results of a genome‐scan for predisposition to aggressive PC using the Utah high‐risk pedigree resource. METHODS We identified 259 subjects with aggressive PC in 57 extended and nuclear families. Parametric and non‐parametric multipoint linkage statistics were calculated for a genome‐wide set of 401 microsatellite markers using the MCLINK software package. Stratification analyses by the number of affected subjects per pedigree (<5, ≥5) and the average age at diagnosis of affected subjects (<70 years, ≥70 years) were also performed. RESULTS No significant results were observed at the genome‐wide level, but suggestive evidence for linkage was observed on chromosomes 9q (HLOD = 2.04) and 14q (HLOD = 2.08); several pedigrees showed individual evidence for linkage at each locus (LOD > 0.58). The subset of pedigrees with earlier age at onset demonstrated nominal linkage evidence on chromosomes 3q (HLOD = 1.79), 8q (HLOD = 1.67), and 20q (HLOD=1.82). The late‐onset subset showed suggestive linkage on chromosome 6p (HLOD = 2.37) and the subset of pedigrees with fewer than five affected subjects showed suggestive linkage on chromosome 10p (HLOD = 1.99). CONCLUSIONS Linkage evidence observed on chromosomes 6p, 8q, and 20q support previously reported PC aggressiveness loci. While these results are encouraging, further research is necessary to identify the gene or genes responsible for PC aggressiveness and surmount the overarching problem of PC heterogeneity. Prostate 67: 605–613, 2007. © 2007 Wiley‐Liss, Inc.