期刊
PROSTATE
卷 71, 期 4, 页码 394-402出版社
WILEY
DOI: 10.1002/pros.21253
关键词
cumulative; adverse features; prostate cancer detection
资金
- Urologic Research Foundation (URF), Northwestern University SPORE [P50, CA90386-05S2]
- Northwestern University Robert H. Lurie Comprehensive Cancer Center [P30, Ca60553]
- deCODE Genetics
BACKGROUND. Several reports suggest that a combination of risk alleles may be associated with prostate cancer (CaP) risk and tumor features. However, their ability to detect CaP and tumor characteristics in patients with a normal PSA (< 4 ng/ml) and non-suspicious digital rectal examination (DRE) remains to be determined. METHODS. We examined 203 men of European ancestry with clinical stage Tic CaP diagnosed at a normal PSA and 611 healthy volunteer controls. The genotypes for 17 different risk alleles were compared between CaP cases and controls. Additional analyses were used to compare the pathologic features between carriers and non-carriers (defined using best-fit genetic model) of these variants. RESULTS. All risk alleles were present at an increased frequency in cases with normal PSA values and DRE compared to controls. Amongst CaP patients, carriers of an increasing number of genetic risk factors (i.e., alleles and positive family history) were at a significantly increased risk of CaP (P-trend < 0.001). Specifically, men with > 10 genetic risk factors had an 11.2-fold risk (95% CI 4.3-29.2) of having the disease compared to men with <= 5 variants. There also was a higher frequency of many the variants amongst men with adverse pathologic features. CONCLUSIONS. A substantial proportion of biopsy-detectable CaP occurs in men with normal PSA levels and negative DRE. In this population, CaP risk alleles and family history are significantly associated with CaP risk and may help predict aggressive disease. Future studies are warranted to determine the utility of incorporating these variants into CaP screening programs. Prostate 71: 394-402, 2011. (C) 2010 Wiley-Liss, Inc.
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