Racial differences in prediction of time to prostate cancer diagnosis in a prospective screening cohort of high-risk men: effect of TMPRSS2 Met160Val.
BACKGROUND
To evaluate the TMPRSS2-ERG gene polymorphism with respect to self-identified race or ethnicity (SIRE), time to prostate cancer (PCA) diagnosis, and screening parameters in the Prostate Cancer Risk Assessment Program, a prospective screening program for high-risk men.


METHODS
A total of 631 men aged between 35 and 69 years were studied. 'High-risk' was defined as ≥ one first degree or two second degree relatives with PCA, any African American (AA) man regardless of familial PCA, and men with BRCA1/2 mutations. Men with elevated prostate-specific antigen (PSA) concentrations or other indications for PCA underwent biopsy. Men were followed from time of study entry to PCA diagnosis. Cox models were used to evaluate time to PCA diagnosis by genotype.


RESULTS
Genotype distribution differed significantly by SIRE (CT/TT vs CC, P < 0.0001). Among 183 Caucasian men with at least one follow-up visit, PCA was more than doubled in men carrying CT/TT vs CC genotypes (hazard ratio = 2.55, 95% CI = 1.14-5.70) after controlling for age and PSA. No association was seen among AA men by TMPRSS2 genotype.


CONCLUSIONS
The T-allele of the Met160Val variant in TMPRSS2, which has been associated with the TMPRSS2-ERG fusion, may be informative of time to PCA diagnosis for a subset of high-risk Caucasian men who are undergoing regular PCA screening. This variant, along with other genetic markers, warrant further study for personalizing PCA screening.
Giri
Veda N
VN
Cancer Prevention and Control Program, Department of Clinical Genetics, Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA. Veda.Giri@fccc.edu
Ruth
Karen
K
Hughes
Lucinda
L
Uzzo
Robert G
RG
Chen
David Y T
DY
Boorjian
Stephen A
SA
Viterbo
Rosalia
R
Rebbeck
Timothy R
TR
D000328:Adult; D000368:Aged; D001706:Biopsy; D055088:Early Detection of Cancer / Q000379:methods*; D004812:Epidemiologic Methods; D005006:Ethnicity; D005787:Gene Frequency; D005820:Genetic Testing; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011467:Prostate / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000208:ethnology* / Q000235:genetics
D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D017430:Prostate-Specific Antigen