Title | Androgen receptor CAG repeat polymorphism and risk of TMPRSS2:ERG-positive prostate cancer. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Yoo 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 |
Journal | Cancer Epidemiol Biomarkers Prev |
Volume | 23 |
Issue | 10 |
Pagination | 2027-31 |
Date Published | 2014 Oct |
ISSN | 1538-7755 |
Keywords | Adult, 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. |
DOI | 10.1158/1055-9965.EPI-14-0020 |
Alternate Journal | Cancer Epidemiol Biomarkers Prev |
PubMed ID | 24925673 |
Grant List | NCICA136578 / / 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.