OBJECTIVE: • To assess whether the carrier status of 35 risk alleles for prostate cancer (CaP) is associated with having unfavourable pathological features in the radical prostatectomy specimen in men with clinically low risk CaP who fulfil commonly accepted criteria as candidates for active surveillance. PATIENTS AND METHODS: • We studied men of European ancestry with CaP who fulfilled the commonly accepted clinical criteria for active surveillance (T1c, prostate-specific antigen <10 ng/mL, biopsy Gleason ≤6, three or fewer positive cores, ≤50% tumour involvement/core) but instead underwent early radical prostatectomy. • We genotyped these men for 35 CaP risk alleles. We defined 'unfavourable' pathological characteristics to be Gleason ≥7 and/or ≥ pT2b in their radical prostatectomy specimen. RESULTS: • In all, 263 men (median age 60 [46-72] years) fulfilled our selection criteria for active surveillance, and 58 of 263 (22.1%) were found to have 'unfavourable' pathological characteristics. • The frequencies of three CaP risk alleles (rs1447295 [8q24], P= 0.004; rs1571801 [9q33.2], P= 0.03; rs11228565 [11q13], P= 0.02) were significantly higher in men with 'unfavourable' pathological characteristics. • Two other risk alleles were proportionately more frequent (rs10934853 [3q21], P= 0.06; rs1859962 [17q24], P= 0.07) but did not achieve nominal statistical significance. • Carriers of any one of the significantly over-represented risk alleles had twice the likelihood of unfavourable tumour features (P= 0.03), and carriers of any two had a sevenfold increased likelihood (P= 0.001). • Receiver-operator curve analysis demonstrated an area under the curve of 0.66, suggesting that the number of single nucleotide polymorphisms carried provided discrimination between men with 'favourable' and 'unfavourable' tumour features in their prostatectomy specimen. CONCLUSION: • In potential candidates for active surveillance, certain CaP risk alleles are more prevalent in patients with 'unfavourable' pathological characteristics in their radical prostatectomy specimen.
OBJECTIVE: • To assess whether the carrier status of 35 risk alleles for prostate cancer (CaP) is associated with having unfavourable pathological features in the radical prostatectomy specimen in men with clinically low risk CaP who fulfil commonly accepted criteria as candidates for active surveillance. PATIENTS AND METHODS: • We studied men of European ancestry with CaP who fulfilled the commonly accepted clinical criteria for active surveillance (T1c, prostate-specific antigen <10 ng/mL, biopsy Gleason ≤6, three or fewer positive cores, ≤50% tumour involvement/core) but instead underwent early radical prostatectomy. • We genotyped these men for 35 CaP risk alleles. We defined 'unfavourable' pathological characteristics to be Gleason ≥7 and/or ≥ pT2b in their radical prostatectomy specimen. RESULTS: • In all, 263 men (median age 60 [46-72] years) fulfilled our selection criteria for active surveillance, and 58 of 263 (22.1%) were found to have 'unfavourable' pathological characteristics. • The frequencies of three CaP risk alleles (rs1447295 [8q24], P= 0.004; rs1571801 [9q33.2], P= 0.03; rs11228565 [11q13], P= 0.02) were significantly higher in men with 'unfavourable' pathological characteristics. • Two other risk alleles were proportionately more frequent (rs10934853 [3q21], P= 0.06; rs1859962 [17q24], P= 0.07) but did not achieve nominal statistical significance. • Carriers of any one of the significantly over-represented risk alleles had twice the likelihood of unfavourable tumour features (P= 0.03), and carriers of any two had a sevenfold increased likelihood (P= 0.001). • Receiver-operator curve analysis demonstrated an area under the curve of 0.66, suggesting that the number of single nucleotide polymorphisms carried provided discrimination between men with 'favourable' and 'unfavourable' tumour features in their prostatectomy specimen. CONCLUSION: • In potential candidates for active surveillance, certain CaP risk alleles are more prevalent in patients with 'unfavourable' pathological characteristics in their radical prostatectomy specimen.
Authors: Laufey T Amundadottir; Patrick Sulem; Julius Gudmundsson; Agnar Helgason; Adam Baker; Bjarni A Agnarsson; Asgeir Sigurdsson; Kristrun R Benediktsdottir; Jean-Baptiste Cazier; Jesus Sainz; Margret Jakobsdottir; Jelena Kostic; Droplaug N Magnusdottir; Shyamali Ghosh; Kari Agnarsson; Birgitta Birgisdottir; Louise Le Roux; Adalheidur Olafsdottir; Thorarinn Blondal; Margret Andresdottir; Olafia Svandis Gretarsdottir; Jon T Bergthorsson; Daniel Gudbjartsson; Arnaldur Gylfason; Gudmar Thorleifsson; Andrei Manolescu; Kristleifur Kristjansson; Gudmundur Geirsson; Helgi Isaksson; Julie Douglas; Jan-Erik Johansson; Katarina Bälter; Fredrik Wiklund; James E Montie; Xiaoying Yu; Brian K Suarez; Carole Ober; Kathleen A Cooney; Henrik Gronberg; William J Catalona; Gudmundur V Einarsson; Rosa B Barkardottir; Jeffrey R Gulcher; Augustine Kong; Unnur Thorsteinsdottir; Kari Stefansson Journal: Nat Genet Date: 2006-05-07 Impact factor: 38.330
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Authors: P Lichtenstein; N V Holm; P K Verkasalo; A Iliadou; J Kaprio; M Koskenvuo; E Pukkala; A Skytthe; K Hemminki Journal: N Engl J Med Date: 2000-07-13 Impact factor: 91.245
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