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      Genetic architecture of prostate cancer in the Ashkenazi Jewish population

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          Abstract

          Background:

          Recently, numerous prostate cancer risk loci have been identified, some of which show association in specific populations. No study has yet investigated whether these single nucleotide polymorphisms (SNPs) are associated with prostate cancer in the Ashkenazi Jewish (AJ) population.

          Methods:

          A total of 29 known prostate cancer risk SNPs were genotyped in 963 prostate cancer cases and 613 controls of AJ ancestry. These data were combined with data from 1241 additional Ashkenazi controls and tested for association with prostate cancer. Correction for multiple testing was performed using the false discovery rate procedure.

          Results:

          Ten of twenty-three SNPs that passed quality control procedures were associated with prostate cancer risk at a false discovery rate of 5%. Of these, nine were originally discovered in studies of individuals of European ancestry. Based on power calculations, the number of significant associations observed is not surprising.

          Conclusion:

          We see no convincing evidence that the genetic architecture of prostate cancer in the AJ population is substantively different from that observed in other populations of European ancestry.

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          Genome-wide association study of prostate cancer identifies a second risk locus at 8q24.

          Meredith Yeager, Nick Orr, Richard Hayes … (2007)
          Recently, common variants on human chromosome 8q24 were found to be associated with prostate cancer risk. While conducting a genome-wide association study in the Cancer Genetic Markers of Susceptibility project with 550,000 SNPs in a nested case-control study (1,172 cases and 1,157 controls of European origin), we identified a new association at 8q24 with an independent effect on prostate cancer susceptibility. The most significant signal is 70 kb centromeric to the previously reported SNP, rs1447295, but shows little evidence of linkage disequilibrium with it. A combined analysis with four additional studies (total: 4,296 cases and 4,299 controls) confirms association with prostate cancer for rs6983267 in the centromeric locus (P = 9.42 x 10(-13); heterozygote odds ratio (OR): 1.26, 95% confidence interval (c.i.): 1.13-1.41; homozygote OR: 1.58, 95% c.i.: 1.40-1.78). Each SNP remained significant in a joint analysis after adjusting for the other (rs1447295 P = 1.41 x 10(-11); rs6983267 P = 6.62 x 10(-10)). These observations, combined with compelling evidence for a recombination hotspot between the two markers, indicate the presence of at least two independent loci within 8q24 that contribute to prostate cancer in men of European ancestry. We estimate that the population attributable risk of the new locus, marked by rs6983267, is higher than the locus marked by rs1447295 (21% versus 9%).
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            Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24.

            Julius Gudmundsson, Patrick Sulem, Andrei Manolescu … (2007)
            Prostate cancer is the most prevalent noncutaneous cancer in males in developed regions, with African American men having among the highest worldwide incidence and mortality rates. Here we report a second genetic variant in the 8q24 region that, in conjunction with another variant we recently discovered, accounts for about 11%-13% of prostate cancer cases in individuals of European descent and 31% of cases in African Americans. We made the current discovery through a genome-wide association scan of 1,453 affected Icelandic individuals and 3,064 controls using the Illumina HumanHap300 BeadChip followed by four replication studies. A key step in the discovery was the construction of a 14-SNP haplotype that efficiently tags a relatively uncommon (2%-4%) susceptibility variant in individuals of European descent that happens to be very common (approximately 42%) in African Americans. The newly identified variant shows a stronger association with affected individuals who have an earlier age at diagnosis.
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              A common variant associated with prostate cancer in European and African populations.

              Laufey T. Amundadottir, Patrick Sulem, Julius Gudmundsson … (2006)
              With the increasing incidence of prostate cancer, identifying common genetic variants that confer risk of the disease is important. Here we report such a variant on chromosome 8q24, a region initially identified through a study of Icelandic families. Allele -8 of the microsatellite DG8S737 was associated with prostate cancer in three case-control series of European ancestry from Iceland, Sweden and the US. The estimated odds ratio (OR) of the allele is 1.62 (P = 2.7 x 10(-11)). About 19% of affected men and 13% of the general population carry at least one copy, yielding a population attributable risk (PAR) of approximately 8%. The association was also replicated in an African American case-control group with a similar OR, in which 41% of affected individuals and 30% of the population are carriers. This leads to a greater estimated PAR (16%) that may contribute to higher incidence of prostate cancer in African American men than in men of European ancestry.
              Article 0 comments Cited 152 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Br J Cancer
                Title: British Journal of Cancer
                Publisher: Nature Publishing Group
                ISSN (Print): 0007-0920
                ISSN (Electronic): 1532-1827
                Publication date (Print): 06 September 2011
                Publication date (Electronic): 09 August 2011
                Volume: 105
                Issue: 6
                Pages: 864-869
                Affiliations
                [1 ]simpleClinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center , New York, NY 10065, USA
                [2 ]simpleProgram in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University; and Research Institute of the McGill University Health Center , Montreal, Quebec H2W 1S6, Canada
                [3 ]simpleDepartment of Psychiatry, Division of Research, The Zucker Hillside Hospital Division of the North Shore – Long Island Jewish Health System , Glen Oaks, NY 11004, USA
                [4 ]simpleThe Institute of Life Sciences, The Hebrew University of Jerusalem , Jerusalem 91904, Israel
                [5 ]simpleProgram in Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center , 1275 York Avenue, Box 337, New York, NY 10065, USA
                Author notes
                [6]

                Current address: NYU Cancer Institute, New York University, New York, NY 10016, USA

                Article
                Publisher Item ID: bjc2011307
                DOI: 10.1038/bjc.2011.307
                PMC ID: 3171013
                PubMed ID: 21829199
                SO-VID: 92781b21-8883-43fe-bd92-51386eddae95
                Copyright © Copyright © 2011 Cancer Research UK
                History
                Date received : 05 April 2011
                Date revision received : 29 June 2011
                Date accepted : 11 July 2011
                Categories
                Subject: Genetics and Genomics

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: association studies,snps,prostate cancer
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: association studies, snps, prostate cancer

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