Aspirin and NSAID use in association with molecular subtypes of prostate cancer defined by TMPRSS2:ERG fusion status.
BACKGROUND
The TMPRSS2:ERG (T2E) gene fusion is the most common rearrangement in prostate cancer (PCa). It is unknown if these molecular subtypes have a different etiology. We evaluated aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) in association with T2E fusion status.


METHODS
Subjects were from a population-based case-control study of PCa. T2E fusion status for prostatectomy cases (n=346) was determined by fluorescence in situ hybridization. Medication use was determined from questionnaires. Logistic regression, controlling for age, race, PCa family history and PSA screening, was used to evaluate the association of T2E fusion status according to medication use.


RESULTS
T2E fusion was present in 171 (49%) cases, with younger cases more likely to be fusion positive (P<0.01). Current aspirin use was associated with a 37% risk reduction of T2E-positive tumors (adjusted odds ratio (OR) 0.63, 95% confidence interval 0.43-0.93). Aspirin use was not associated with T2E negative PCa (adjusted OR 0.99, 0.69-1.42). There were no associations between PCa fusion status and use of nonaspirin NSAIDs or acetaminophen.


CONCLUSIONS
Aspirin was associated with a significant reduction in the relative risk of T2E fusion positive, but not T2E negative, PCa. As inflammation and androgen pathways are implicated in prostate carcinogenesis, additional studies of anti-inflammatory medications in relation to these PCa subtypes are warranted.
Department of Urology, University of Washington School of Medicine, Seattle, WA, USA.|Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
J L
JL
Wright
Department of Urology, University of Washington School of Medicine, Seattle, WA, USA.
L
L
Chéry
Department of Urology, University of Washington School of Medicine, Seattle, WA, USA.
S
S
Holt
Department of Urology, University of Washington School of Medicine, Seattle, WA, USA.|Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
D W
DW
Lin
Department of Urology, University of Ulm, Ulm, Germany.|Institute of Human Genetics, University of Ulm, Ulm, Germany.
M
M
Luedeke
Department of Urology, University of Ulm, Ulm, Germany.|Institute of Human Genetics, University of Ulm, Ulm, Germany.
A E
AE
Rinckleb
Department of Urology, University of Ulm, Ulm, Germany.|Institute of Human Genetics, University of Ulm, Ulm, Germany.
C
C
Maier
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Department of Epidemiology, University of Washington School of Public Health, Seattle, WA, USA.
J L
JL
Stanford
D000328:Adult; D000368:Aged; D000728:Androgens / Q000235:genetics / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D001241:Aspirin / Q000008:administration & dosage*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000145:classification / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
D000728:Androgens; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D001241:Aspirin