Androgen receptor CAG repeat polymorphism and risk of TMPRSS2:ERG-positive prostate cancer.

TitleAndrogen receptor CAG repeat polymorphism and risk of TMPRSS2:ERG-positive prostate cancer.
Publication TypeJournal Article
Year of Publication2014
AuthorsYoo S, Pettersson A, Jordahl KM, Lis RT, Lindstrom S, Meisner A, Nuttall EJ, Stack EC, Stampfer MJ, Kraft P, Brown M, Loda M, Giovannucci EL, Kantoff PW, Mucci LA
JournalCancer Epidemiol Biomarkers Prev
Volume23
Issue10
Pagination2027-31
Date Published2014 Oct
ISSN1538-7755
KeywordsAdult, Aged, Aged, 80 and over, Case-Control Studies, Genetic Predisposition to Disease, Genotype, Humans, Male, Middle Aged, Oncogene Proteins, Fusion, Prostatic Neoplasms, Receptors, Androgen, Trinucleotide Repeats
Abstract

BACKGROUND: The androgen receptor (AR) is an essential gene in prostate cancer pathogenesis and progression. Genetic variation in AR exists, including a polymorphic CAG repeat sequence that is inversely associated with transcriptional activity. Experimental data suggest that heightened AR activity facilitates formation of TMPRSS2:ERG, a gene fusion present in approximately 50% of tumors of patients with prostate cancer.

METHODS: We undertook a nested case-control study to investigate the hypothesis that shorter CAG repeat length would be associated with prostate cancer risk defined by TMPRSS2:ERG status. The study included 291 men with prostate cancer (147 ERG-positive) and 1,221 cancer-free controls. ORs and 95% confidence intervals (CI) were calculated using logistic regression.

RESULTS: Median CAG repeat length (interquartile range) among controls was 22 (20-24). Men with shorter CAG repeats had an increased risk of ERG-positive (OR, 1.07 per 1 repeat decrease; 95% CI, 1.00-1.14), but not ERG-negative prostate cancer (OR, 0.99 per 1 repeat decrease; 95% CI, 0.93-1.05).

CONCLUSIONS: These data suggest that shorter CAG repeats are specifically associated with development of TMPRSS2:ERG-positive prostate cancer.

IMPACT: Our results provide supportive evidence that androgen signaling underlies the development of prostate tumors that harbor TMPRSS2:ERG. Moreover, these results suggest that TMPRSS2:ERG may represent a unique molecular subtype of prostate cancer with an etiology distinct from TMPRSS2:ERG-negative disease.

DOI10.1158/1055-9965.EPI-14-0020
Alternate JournalCancer Epidemiol Biomarkers Prev
PubMed ID24925673
Grant ListNCICA136578 / / PHS HHS / United States
CA141298 / CA / NCI NIH HHS / United States
UM1CA167552 / CA / NCI NIH HHS / United States
CA097193 / CA / NCI NIH HHS / United States
P50CA090381-08 / CA / NCI NIH HHS / United States
U01CA098233 / CA / NCI NIH HHS / United States
Related Faculty: 
Massimo Loda, M.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700