|Grant Number:||3R01CA079596-10S1 Interpret this number|
|Primary Investigator:||Cooney, Kathleen|
|Organization:||University Of Michigan At Ann Arbor|
|Project Title:||Genetic Analysis of Hereditary Prostate Cancer Families|
DESCRIPTION (provided by applicant): The recognition that prostate cancer clusters within families has led many research teams including our own to collect families with multiple cases of prostate cancer for linkage studies. Unfortunately, despite the collection and analysis of a large number of such families, the major genes that contribute to inherit prostate cancer susceptibility have been difficult to fully characterize. At least eight loci have been proposed and further studies are now required to determine the most clinically important prostate cancer predisposition genes. The University of Michigan Prostate Cancer Genetics Project (PCGP) was established in 1995 as a family based study of inherited prostate cancer susceptibility. A genome wide linkage scans was recently completed using 176 multiplex PCGP families, which has implicated several new genomic regions for additional study. The strongest evidence for prostate cancer linkage was on chromosome 17 adjacent to the BRCA1 gene. Mutations in the BRCA1 gene have been shown to increase the risk of breast and ovarian cancer in women as well as prostate cancer in men, however BRCA1 mutations have not been previously identified in prostate cancer families. To further characterize the role of BRCA1 in hereditary prostate cancer and to define other prostate cancer susceptibility genes and their associated clinical syndromes, the following three Specific Aims are proposed: 1) To evaluate the role of the breast cancer gene BRCA1 as a prostate cancer susceptibility gene in PCGP families, 2) to localize and characterize candidate prostate cancer susceptibility genes in PCGP families, 3) To identify prostate cancer susceptibility genes that specifically influences the risk of developing clinically aggressive prostate cancer. Completion of these aims will improve our understanding of the genes that predispose men to prostate cancer as well as the clinical syndromes associated with specific gene mutations. Ultimately, this information may have clinical utility to identify those men at highest risk of prostate cancer who may benefit from early detection and/or chemoprevention strategies.
HOXB13 is a susceptibility gene for prostate cancer: results from the International Consortium for Prostate Cancer Genetics (ICPCG).
Authors: Xu J, Lange EM, Lu L, Zheng SL, Wang Z, Thibodeau SN, Cannon-Albright LA, Teerlink CC, Camp NJ, Johnson AM, Zuhlke KA, Stanford JL, Ostrander EA, Wiley KE, Isaacs SD, Walsh PC, Maier C, Luedeke M, Vogel W, Schleutker J, Wahlfors T, Tammela T, Schaid D, McDonnell SK, DeRycke MS, Cancel-Tassin G, Cussenot O, Wiklund F, Grönberg H, Eeles R, Easton D, Kote-Jarai Z, Whittemore AS, Hsieh CL, Giles GG, Hopper JL, Severi G, Catalona WJ, Mandal D, Ledet E, Foulkes WD, Hamel N, Mahle L, Moller P, Powell I, Bailey-Wilson JE, Carpten JD, Seminara D, Cooney KA, Isaacs WB, International Consortium for Prostate Cancer Genetics
Source: Hum Genet, 2013 Jan;132(1), p. 5-14.
EPub date: 2012 Oct 12.
Identification of a novel NBN truncating mutation in a family with hereditary prostate cancer.
Authors: Zuhlke KA, Johnson AM, Okoth LA, Stoffel EM, Robbins CM, Tembe WA, Salinas CA, Zheng SL, Xu J, Carpten JD, Lange EM, Isaacs WB, Cooney KA
Source: Fam Cancer, 2012 Dec;11(4), p. 595-600.
Germline mutations in HOXB13 and prostate-cancer risk.
Authors: Ewing CM, Ray AM, Lange EM, Zuhlke KA, Robbins CM, Tembe WD, Wiley KE, Isaacs SD, Johng D, Wang Y, Bizon C, Yan G, Gielzak M, Partin AW, Shanmugam V, Izatt T, Sinari S, Craig DW, Zheng SL, Walsh PC, Montie JE, Xu J, Carpten JD, Isaacs WB, Cooney KA
Source: N Engl J Med, 2012 Jan 12;366(2), p. 141-9.
Early onset prostate cancer has a significant genetic component.
Authors: Lange EM, Salinas CA, Zuhlke KA, Ray AM, Wang Y, Lu Y, Ho LA, Luo J, Cooney KA
Source: Prostate, 2012 Feb 1;72(2), p. 147-56.
EPub date: 2011 May 2.
Hereditary prostate cancer as a feature of Lynch syndrome.
Authors: Bauer CM, Ray AM, Halstead-Nussloch BA, Dekker RG, Raymond VM, Gruber SB, Cooney KA
Source: Fam Cancer, 2011 Mar;10(1), p. 37-42.
Evidence for an association between prostate cancer and chromosome 8q24 and 10q11 genetic variants in African American men: the Flint Men's Health Study.
Authors: Wang Y, Ray AM, Johnson EK, Zuhlke KA, Cooney KA, Lange EM
Source: Prostate, 2011 Feb 15;71(3), p. 225-31.
EPub date: 2010 Aug 17.
Genetic variation in adiponectin (ADIPOQ) and the type 1 receptor (ADIPOR1), obesity and prostate cancer in African Americans.
Authors: Beebe-Dimmer JL, Zuhlke KA, Ray AM, Lange EM, Cooney KA
Source: Prostate Cancer Prostatic Dis, 2010 Dec;13(4), p. 362-8.
EPub date: 2010 Aug 10.
Absence of truncating BRIP1 mutations in chromosome 17q-linked hereditary prostate cancer families.
Authors: Ray AM, Zuhlke KA, Johnson GR, Levin AM, Douglas JA, Lange EM, Cooney KA
Source: Br J Cancer, 2009 Dec 15;101(12), p. 2043-7.
EPub date: 2009 Nov 24.
Genome-wide linkage scan for prostate cancer susceptibility from the University of Michigan Prostate Cancer Genetics Project: suggestive evidence for linkage at 16q23.
Authors: Lange EM, Beebe-Dimmer JL, Ray AM, Zuhlke KA, Ellis J, Wang Y, Walters S, Cooney KA
Source: Prostate, 2009 Mar 1;69(4), p. 385-91.
Semiparametric Bayesian modeling of random genetic effects in family-based association studies.
Authors: Zhang L, Mukherjee B, Hu B, Moreno V, Cooney KA
Source: Stat Med, 2009 Jan 15;28(1), p. 113-39.
Family-based samples can play an important role in genetic association studies.
Authors: Lange EM, Sun J, Lange LA, Zheng SL, Duggan D, Carpten JD, Gronberg H, Isaacs WB, Xu J, Chang BL
Source: Cancer Epidemiol Biomarkers Prev, 2008 Sep;17(9), p. 2208-14.
Chromosome 17q12 variants contribute to risk of early-onset prostate cancer.
Authors: Levin AM, Machiela MJ, Zuhlke KA, Ray AM, Cooney KA, Douglas JA
Source: Cancer Res, 2008 Aug 15;68(16), p. 6492-5.
Identification and characterization of novel SNPs in CHEK2 in Ashkenazi Jewish men with prostate cancer.
Authors: Tischkowitz MD, Yilmaz A, Chen LQ, Karyadi DM, Novak D, Kirchhoff T, Hamel N, Tavtigian SV, Kolb S, Bismar TA, Aloyz R, Nelson PS, Hood L, Narod SA, White KA, Ostrander EA, Isaacs WB, Offit K, Cooney KA, Stanford JL, Foulkes WD
Source: Cancer Lett, 2008 Oct 18;270(1), p. 173-80.
EPub date: 2008 Jun 20.
Chromosome 8q24 markers: risk of early-onset and familial prostate cancer.
Authors: Beebe-Dimmer JL, Levin AM, Ray AM, Zuhlke KA, Machiela MJ, Halstead-Nussloch BA, Johnson GR, Cooney KA, Douglas JA
Source: Int J Cancer, 2008 Jun 15;122(12), p. 2876-9.
Analysis of the gene coding for the BRCA2-interacting protein PALB2 in hereditary prostate cancer.
Authors: Tischkowitz M, Sabbaghian N, Ray AM, Lange EM, Foulkes WD, Cooney KA
Source: Prostate, 2008 May 1;68(6), p. 675-8.
Genetic polymorphisms in CYP17, CYP3A4, CYP19A1, SRD5A2, IGF-1, and IGFBP-3 and prostate cancer risk in African-American men: the Flint Men's Health Study.
Authors: Sarma AV, Dunn RL, Lange LA, Ray A, Wang Y, Lange EM, Cooney KA
Source: Prostate, 2008 Feb 15;68(3), p. 296-305.
Sequence variation in alpha-methylacyl-CoA racemase and risk of early-onset and familial prostate cancer.
Authors: Levin AM, Zuhlke KA, Ray AM, Cooney KA, Douglas JA
Source: Prostate, 2007 Oct 1;67(14), p. 1507-13.
Common variation in the BRCA1 gene and prostate cancer risk.
Authors: Douglas JA, Levin AM, Zuhlke KA, Ray AM, Johnson GR, Lange EM, Wood DP, Cooney KA
Source: Cancer Epidemiol Biomarkers Prev, 2007 Jul;16(7), p. 1510-6.
EPub date: 2007 Jun 21.
Association between germline variation in the FHIT gene and prostate cancer in Caucasians and African Americans.
Authors: Levin AM, Ray AM, Zuhlke KA, Douglas JA, Cooney KA
Source: Cancer Epidemiol Biomarkers Prev, 2007 Jun;16(6), p. 1294-7.
Multiple regions within 8q24 independently affect risk for prostate cancer.
Authors: 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
Source: Nat Genet, 2007 May;39(5), p. 638-44.
EPub date: 2007 Apr 1.
Fine-mapping the putative chromosome 17q21-22 prostate cancer susceptibility gene to a 10 cM region based on linkage analysis.
Authors: Lange EM, Robbins CM, Gillanders EM, Zheng SL, Xu J, Wang Y, White KA, Chang BL, Ho LA, Trent JM, Carpten JD, Isaacs WB, Cooney KA
Source: Hum Genet, 2007 Mar;121(1), p. 49-55.
EPub date: 2006 Nov 21.
Association between family history of prostate and breast cancer among African-American men with prostate cancer.
Authors: Beebe-Dimmer JL, Drake EA, Dunn RL, Bock CH, Montie JE, Cooney KA
Source: Urology, 2006 Nov;68(5), p. 1072-6.
EPub date: 2006 Nov 7.
Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men.
Authors: 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
Source: Proc Natl Acad Sci U S A, 2006 Sep 19;103(38), p. 14068-73.
EPub date: 2006 Aug 31.
Prohibitin mutations are uncommon in prostate cancer families linked to chromosome 17q.
Authors: White KA, Lange EM, Ray AM, Wojno KJ, Cooney KA
Source: Prostate Cancer Prostatic Dis, 2006;9(3), p. 298-302.
EPub date: 2006 May 30.
Genome-wide linkage scan for prostate cancer aggressiveness loci using families from the University of Michigan Prostate Cancer Genetics Project.
Authors: Slager SL, Zarfas KE, Brown WM, Lange EM, McDonnell SK, Wojno KJ, Cooney KA
Source: Prostate, 2006 Feb 1;66(2), p. 173-9.
Identifying susceptibility genes for prostate cancer--a family-based association study of polymorphisms in CYP17, CYP19, CYP11A1, and LH-beta.
Authors: Douglas JA, Zuhlke KA, Beebe-Dimmer J, Levin AM, Gruber SB, Wood DP, Cooney KA
Source: Cancer Epidemiol Biomarkers Prev, 2005 Aug;14(8), p. 2035-9.
Decreasing age at prostate cancer diagnosis over successive generations in prostate cancer families.
Authors: Bock CH, Peyser PA, Montie JE, Cooney KA
Source: Prostate, 2005 Jun 15;64(1), p. 60-6.