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Cancer Epidemiol Biomarkers Prev. 2014 Oct;23(10):2027-31. doi: 10.1158/1055-9965.EPI-14-0020. Epub 2014 Jun 12.

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

Author information

1
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
2
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts. lmucci@hsph.harvard.edu apetters@hsph.harvard.edu.
3
Department of Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts. Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts.
4
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts. Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
5
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts. Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts.
6
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
7
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
8
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts. Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. lmucci@hsph.harvard.edu apetters@hsph.harvard.edu.

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.

PMID:
24925673
PMCID:
PMC4184923
DOI:
10.1158/1055-9965.EPI-14-0020
[Indexed for MEDLINE]
Free PMC Article

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