Identification of new genetic risk factors for prostate cancer.
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ABSTRACT:
SUBMITTER: Guy M
PROVIDER: S-EPMC3735221 | biostudies-literature | 2009 Jan
REPOSITORIES: biostudies-literature
Publications
Identification of new genetic risk factors for prostate cancer.
Guy Michelle M Kote-Jarai Zsofia Z Giles Graham G GG Al Olama Ali Amin AA Jugurnauth Sarah K SK Mulholland Shani S Leongamornlert Daniel A DA Edwards Stephen M SM Morrison Jonathan J Field Helen I HI Southey Melissa C MC Severi Gianluca G Donovan Jenny L JL Hamdy Freddie C FC Dearnaley David P DP Muir Kenneth R KR Smith Charmaine C Bagnato Melisa M Ardern-Jones Audrey T AT Hall Amanda L AL O'Brien Lynne T LT Gehr-Swain Beatrice N BN Wilkinson Rosemary A RA Cox Angela A Lewis Sarah S Brown Paul M PM Jhavar Sameer G SG Tymrakiewicz Malgorzata M Lophatananon Artitaya A Bryant Sarah L SL Horwich Alan A Huddart Robert A RA Khoo Vincent S VS Parker Christopher C CC Woodhouse Christopher J CJ Thompson Alan A Christmas Tim T Ogden Chris C Fisher Cyril C Jameson Charles C Cooper Colin S CS English Dallas R DR Hopper John L JL Neal David E DE Easton Douglas F DF Eeles Rosalind A RA
Asian journal of andrology 20081201 1
There is evidence that a substantial part of genetic predisposition to prostate cancer (PCa) may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a study and seven new regions of the genome linked to PCa risk have been identified. Three of these loci contain candidate susceptibility genes: MSMB, LMTK2 and KLK2/3. The MSMB and KLK2/3 genes may be useful for PCa screening, and the LMTK2 gene might provide a potential therapeutic t ...[more]
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Project description:BackgroundMany SNPs influence prostate cancer risk. To what extent genetic risk can be reduced by environmental factors is unknown.MethodsWe evaluated effect modification by environmental factors of the association between susceptibility SNPs and prostate cancer in 1,230 incident prostate cancer cases and 1,361 controls, all white and similar ages, nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Trial. Genetic risk scores were calculated as number of risk alleles for 20 validated SNPs. We estimated the association between higher genetic risk (≥12 SNPs) and prostate cancer within environmental factor strata and tested for interaction.ResultsMen with ≥12 risk alleles had 1.98, 2.04, and 1.91 times the odds of total, advanced, and nonadvanced prostate cancer, respectively. These associations were attenuated with the use of selenium supplements, aspirin, ibuprofen, and higher vegetable intake. For selenium, the attenuation was most striking for advanced prostate cancer: compared with <12 alleles and no selenium, the OR for ≥12 alleles was 2.06 [95% confidence interval (CI), 1.67-2.55] in nonusers and 0.99 (0.38-2.58) in users (Pinteraction = 0.031). Aspirin had the most marked attenuation for nonadvanced prostate cancer: compared with <12 alleles and nonusers, the OR for ≥12 alleles was 2.25 (1.69-3.00) in nonusers and 1.70 (1.25-2.32) in users (Pinteraction = 0.009). This pattern was similar for ibuprofen (Pinteraction = 0.023) and vegetables (Pinteraction = 0.010).ConclusionsThis study suggests that selenium supplements may reduce genetic risk of advanced prostate cancer, whereas aspirin, ibuprofen, and vegetables may reduce genetic risk of nonadvanced prostate cancer.ImpactThe effect of genetic factors on prostate cancer risk may vary by lifestyle interventions.
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