Advertisement

Human Genetics

, 126:637 | Cite as

Results from a prostate cancer admixture mapping study in African-American men

  • Cathryn Hufford BockEmail author
  • Ann G. Schwartz
  • Julie J. Ruterbusch
  • Albert M. Levin
  • Christine Neslund-Dudas
  • Susan J. Land
  • Angela S. Wenzlaff
  • David Reich
  • Paul McKeigue
  • Wei Chen
  • Elisabeth I. Heath
  • Isaac J. Powell
  • Rick A. Kittles
  • Benjamin A. Rybicki
Original Investigation

Abstract

There are considerable racial disparities in prostate cancer risk, with a 60% higher incidence rate among African-American (AA) men compared with European-American (EA) men, and a 2.4-fold higher mortality rate in AA men than in EA men. Recently, studies have implicated several African-ancestry associated prostate cancer susceptibility loci on chromosome 8q24. In the current study, we performed admixture mapping in AA men from two independent case–control studies of prostate cancer to confirm the 8q24 ancestry association and also identify other genomic regions that may harbor prostate cancer susceptibility genes. A total of 482 cases and 261 controls were genotyped for 1,509 ancestry informative markers across the genome. The mean estimated individual admixture proportions were 20% European and 80% African. The most significant observed increase in European ancestry occurred at rs2141360 on chromosome 7q31 in both the case-only (P = 0.0000035) and case–control analyses. The most significant observed increase in African ancestry across the genome occurred at a locus on chromosome 5q35 identified by SNPs rs7729084 (case-only analysis P = 0.002), and rs12474977 (case–control analysis P = 0.004), which are separated by 646 kb and were adjacent to one another on the panel. On chromosome 8, rs4367565 was associated with the greatest excess African ancestry in both the case-only and case–control analyses (case-only and case–control P = 0.02), confirming previously reported African-ancestry associations with chromosome 8q24. In conclusion, we confirmed ancestry associations on 8q24, and identified additional ancestry-associated regions potentially harboring prostate cancer susceptibility loci.

Keywords

Prostate Cancer Risk African Ancestry Prostate Cancer Case Aggressive Prostate Cancer Admixture Mapping 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This project was supported by the U.S. Department of Defense W81XWH 06-1-0181, NIH/NIEHS 5 R01 ES11126-03, NCI 1U54CA091431-010001, Wayne State University Research Enhancement Program, and the Barbara Ann Karmanos Cancer Institute.

References

  1. Casey G, Neville PJ, Liu X, Plummer SJ, Cicek MS, Krumroy LM, Curran AP, McGreevy MR, Catalona WJ, Klein EA, Witte JS (2006) Podocalyxin variants and risk of prostate cancer and tumor aggressiveness. Hum Mol Genet 15:735–741CrossRefPubMedGoogle Scholar
  2. Cerhan JR, Parker AS, Putnam SD, Chiu BC, Lynch CF, Cohen MB, Torner JC, Cantor KP (1999) Family history and prostate cancer risk in a population-based cohort of Iowa men. Cancer Epidemiol Biomarkers Prev 8:53–60PubMedGoogle Scholar
  3. Easton DF, Schaid DJ, Whittemore AS, Isaacs WJ (2003) Where are the prostate cancer genes? A summary of eight genome-wide searches. Prostate 57:261–269CrossRefPubMedGoogle Scholar
  4. Freedman ML, Haiman CA, Patterson N, McDonald GJ, Tandon A, Waliszewska A, Penney K, Steen RG, Ardlie K, John EM, Oakley-Girvan I, Whittemore AS, Cooney KA, Ingles SA, Altshuler D, Henderson BE, Reich D (2006) Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men. Proc Natl Acad Sci USA 103:14068–14073CrossRefPubMedGoogle Scholar
  5. Ghoussaini M, Song H, Koessler T, Al Olama AA, Kote-Jarai Z, Driver KE, Pooley KA, Ramus SJ, Kjaer SK, Hogdall E, DiCioccio RA, Whittemore AS, Gayther SA, Giles GG, Guy M, Edwards SM, Morrison J, Donovan JL, Hamdy FC, Dearnaley DP, Ardern-Jones AT, Hall AL, O’Brien LT, Gehr-Swain BN, Wilkinson RA, Brown PM, Hopper JL, Neal DE, Pharoah PD, Ponder BA, Eeles RA, Easton DF, Dunning AM (2008) Multiple loci with different cancer specificities within the 8q24 gene desert. J Natl Cancer Inst 100:962–966CrossRefPubMedGoogle Scholar
  6. Goddard KA, Witte JS, Suarez BK, Catalona WJ, Olson JM (2001) Model-free linkage analysis with covariates confirms linkage of prostate cancer to chromosomes 1 and 4. Am J Hum Genet 68:1197–1206CrossRefPubMedGoogle Scholar
  7. Gudmundsson J, Sulem P, Manolescu A, Amundadottir LT, Gudbjartsson D, Helgason A, Rafnar T, Bergthorsson JT, Agnarsson BA, Baker A, Sigurdsson A, Benediktsdottir KR, Jakobsdottir M, Xu J, Blondal T, Kostic J, Sun J, Ghosh S, Stacey SN, Mouy M, Saemundsdottir J, Backman VM, Kristjansson K, Tres A, Partin AW, Albers-Akkers MT, Godino-Ivan Marcos J, Walsh PC, Swinkels DW, Navarrete S, Isaacs SD, Aben KK, Graif T, Cashy J, Ruiz-Echarri M, Wiley KE, Suarez BK, Witjes JA, Frigge M, Ober C, Jonsson E, Einarsson GV, Mayordomo JI, Kiemeney LA, Isaacs WB, Catalona WJ, Barkardottir RB, Gulcher JR, Thorsteinsdottir U, Kong A, Stefansson K (2007) Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24. Nat Genet 39:631–637CrossRefPubMedGoogle Scholar
  8. Haiman CA, Patterson N, Freedman ML, Myers SR, Pike MC, Waliszewska A, Neubauer J, Tandon A, Schirmer C, McDonald GJ, Greenway SC, Stram DO, Le Marchand L, Kolonel LN, Frasco M, Wong D, Pooler LC, Ardlie K, Oakley-Girvan I, Whittemore AS, Cooney KA, John EM, Ingles SA, Altshuler D, Henderson BE, Reich D (2007) Multiple regions within 8q24 independently affect risk for prostate cancer. Nat Genet 39:638–644CrossRefPubMedGoogle Scholar
  9. Hoggart CJ, Parra EJ, Shriver MD, Bonilla C, Kittles RA, Clayton DG, McKeigue PM (2003) Control of confounding of genetic associations in stratified populations. Am J Hum Genet 72:1492–1504CrossRefPubMedGoogle Scholar
  10. Hoggart CJ, Shriver MD, Kittles RA, Clayton DG, McKeigue PM (2004) Design and analysis of admixture mapping studies. Am J Hum Genet 74:965–978CrossRefPubMedGoogle Scholar
  11. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ (2008) Cancer statistics, 2008. CA Cancer J Clin 58:71–96CrossRefPubMedGoogle Scholar
  12. Neville PJ, Conti DV, Paris PL, Levin H, Catalona WJ, Suarez BK, Witte JS, Casey G (2002) Prostate cancer aggressiveness locus on chromosome 7q32–q33 identified by linkage and allelic imbalance studies. Neoplasia (New York) 4:424–431Google Scholar
  13. Paiss T, Worner S, Kurtz F, Haeussler J, Hautmann RE, Gschwend JE, Herkommer K, Vogel W (2003) Linkage of aggressive prostate cancer to chromosome 7q31–33 in German prostate cancer families. Eur J Hum Genet 11:17–22CrossRefPubMedGoogle Scholar
  14. Reich D, Patterson N, De Jager PL, McDonald GJ, Waliszewska A, Tandon A, Lincoln RR, DeLoa C, Fruhan SA, Cabre P, Bera O, Semana G, Kelly MA, Francis DA, Ardlie K, Khan O, Cree BA, Hauser SL, Oksenberg JR, Hafler DA (2005) A whole-genome admixture scan finds a candidate locus for multiple sclerosis susceptibility. Nat Genet 37:1113–1118CrossRefPubMedGoogle Scholar
  15. Robbins C, Torres JB, Hooker S, Bonilla C, Hernandez W, Candreva A, Ahaghotu C, Kittles R, Carpten J (2007) Confirmation study of prostate cancer risk variants at 8q24 in African Americans identifies a novel risk locus. Genome Res 17:1717–1722CrossRefPubMedGoogle Scholar
  16. Rybicki BA, Neslund-Dudas C, Nock NL, Schultz LR, Eklund L, Rosbolt J, Bock CH, Monaghan KG (2006) Prostate cancer risk from occupational exposure to polycyclic aromatic hydrocarbons interacting with the GSTP1 Ile105Val polymorphism. Cancer Detect Prev 30:412–422CrossRefPubMedGoogle Scholar
  17. Schaid DJ (2004) The complex genetic epidemiology of prostate cancer. Hum Mol Genet 13(1): R103–R121Google Scholar
  18. Schaid DJ, Stanford JL, McDonnell SK, Suuriniemi M, McIntosh L, Karyadi DM, Carlson EE, Deutsch K, Janer M, Hood L, Ostrander EA (2007) Genome-wide linkage scan of prostate cancer Gleason score and confirmation of chromosome 19q. Hum Genet 121:729–735CrossRefPubMedGoogle Scholar
  19. Schumacher FR, Feigelson HS, Cox DG, Haiman CA, Albanes D, Buring J, Calle EE, Chanock SJ, Colditz GA, Diver WR, Dunning AM, Freedman ML, Gaziano JM, Giovannucci E, Hankinson SE, Hayes RB, Henderson BE, Hoover RN, Kaaks R, Key T, Kolonel LN, Kraft P, Le Marchand L, Ma J, Pike MC, Riboli E, Stampfer MJ, Stram DO, Thomas G, Thun MJ, Travis R, Virtamo J, Andriole G, Gelmann E, Willett WC, Hunter DJ (2007) A common 8q24 variant in prostate and breast cancer from a large nested case-control study. Cancer Res 67:2951–2956CrossRefPubMedGoogle Scholar
  20. Slager SL, Zarfas KE, Brown WM, Lange EM, McDonnell SK, Wojno KJ, Cooney KA (2006) Genome-wide linkage scan for prostate cancer aggressiveness loci using families from the University of Michigan Prostate Cancer Genetics Project. Prostate 66:173–179CrossRefPubMedGoogle Scholar
  21. Smith MW, Patterson N, Lautenberger JA, Truelove AL, McDonald GJ, Waliszewska A, Kessing BD, Malasky MJ, Scafe C, Le E, De Jager PL, Mignault AA, Yi Z, De The G, Essex M, Sankale JL, Moore JH, Poku K, Phair JP, Goedert JJ, Vlahov D, Williams SM, Tishkoff SA, Winkler CA, De La Vega FM, Woodage T, Sninsky JJ, Hafler DA, Altshuler D, Gilbert DA, O’Brien SJ, Reich D (2004) A high-density admixture map for disease gene discovery in African Americans. Am J Hum Genet 74:1001–1013CrossRefPubMedGoogle Scholar
  22. Suuriniemi M, Agalliu I, Schaid DJ, Johanneson B, McDonnell SK, Iwasaki L, Stanford JL, Ostrander EA (2007) Confirmation of a positive association between prostate cancer risk and a locus at chromosome 8q24. Cancer Epidemiol Biomarkers Prev 16:809–814CrossRefPubMedGoogle Scholar
  23. Wang L, McDonnell SK, Slusser JP, Hebbring SJ, Cunningham JM, Jacobsen SJ, Cerhan JR, Blute ML, Schaid DJ, Thibodeau SN (2007) Two common chromosome 8q24 variants are associated with increased risk for prostate cancer. Cancer Res 67:2944–2950CrossRefPubMedGoogle Scholar
  24. Witte JS, Goddard KAB, Conti DV, Elston RC, Lin JL, Suarez BK, Broman KW, Burmester JK, Weber JL, Catalona WJ (2000) Genomewide scan for prostate cancer-aggressiveness loci. Am J Hum Genet 67:92–99CrossRefPubMedGoogle Scholar
  25. Witte JS, Suarez BK, Thiel B, Lin J, Yu A, Banerjee TK, Burmester JK, Casey G, Catalona WJ (2003) Genome-wide scan of brothers: replication and fine mapping of prostate cancer susceptibility and aggressiveness loci. Prostate 57:298–308CrossRefPubMedGoogle Scholar
  26. Yajnik V, Paulding C, Sordella R, McClatchey AI, Saito M, Wahrer DC, Reynolds P, Bell DW, Lake R, van den Heuvel S, Settleman J, Haber DA (2003) DOCK4, a GTPase activator, is disrupted during tumorigenesis. Cell 112:673–684CrossRefPubMedGoogle Scholar
  27. Yeager M, Orr N, Hayes RB, Jacobs KB, Kraft P, Wacholder S, Minichiello MJ, Fearnhead P, Yu K, Chatterjee N, Wang Z, Welch R, Staats BJ, Calle EE, Feigelson HS, Thun MJ, Rodriguez C, Albanes D, Virtamo J, Weinstein S, Schumacher FR, Giovannucci E, Willett WC, Cancel-Tassin G, Cussenot O, Valeri A, Andriole GL, Gelmann EP, Tucker M, Gerhard DS, Fraumeni JF Jr, Hoover R, Hunter DJ, Chanock SJ, Thomas G (2007) Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat Genet 39:645–649CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Cathryn Hufford Bock
    • 1
    • 2
    Email author
  • Ann G. Schwartz
    • 1
    • 2
  • Julie J. Ruterbusch
    • 2
  • Albert M. Levin
    • 3
  • Christine Neslund-Dudas
    • 3
  • Susan J. Land
    • 1
  • Angela S. Wenzlaff
    • 2
  • David Reich
    • 4
    • 5
  • Paul McKeigue
    • 6
  • Wei Chen
    • 1
    • 2
  • Elisabeth I. Heath
    • 1
    • 2
  • Isaac J. Powell
    • 1
    • 2
  • Rick A. Kittles
    • 7
  • Benjamin A. Rybicki
    • 2
    • 3
  1. 1.Wayne State University School of MedicineDetroitUSA
  2. 2.Karmanos Cancer InstituteDetroitUSA
  3. 3.Henry Ford Health SystemDetroitUSA
  4. 4.Harvard Medical SchoolBostonUSA
  5. 5.Broad Institute of Harvard and MITCambridgeUSA
  6. 6.Western General HospitalUniversity of EdinburghEdinburghUK
  7. 7.University of ChicagoChicagoUSA

Personalised recommendations