Prostate cancer risk alleles significantly improve disease detection and are associated with aggressive features in patients with a "normal" prostate specific antigen and digital rectal examination

Brian T. Helfand, Donghui Kan, Parth Modi, William J. Catalona

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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 T1c 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 â5 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 " 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.

Original languageEnglish (US)
Pages (from-to)394-402
Number of pages9
JournalProstate
Volume71
Issue number4
DOIs
StatePublished - Mar 1 2011

Keywords

  • adverse features
  • cumulative
  • prostate cancer detection

ASJC Scopus subject areas

  • Oncology
  • Urology

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