Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Cancer Prone Disease Section Review Hereditary prostate cancer Johanna Schleutker Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland (JS) Published in Atlas Database: June 2008 Online updated version : http://AtlasGeneticsOncology.org/Kprones/HeredProstateCancerID10055.html DOI: 10.4267/2042/44502 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2009 Atlas of Genetics and Cytogenetics in Oncology and Haematology increases with increasing number of affected relatives and their decreasing age at diagnosis. The incidence and absolute risk of prostate cancer varies among different ethnic backgrounds. However, increase in relative risk for males with a positive family history of the disease is essentially the same in all studied populations. In epidemiological studies increased risk of breast cancer, ovarian cancer, gastric cancer and liver cancer, Hodgkin's disease, leukaemia and melanoma have been detected in relatives of prostate cancer patients. Identity Alias: Familial prostate cancer Note: Form of prostate cancer with a familial background, OMIM: 176807, 601518. Inheritance: The inherited form is predicted to account for 5-9% of prostate cancers. Multiple forms of inheritance have been suggested based on segregation analyses: autosomal dominant (rare, high-penetrant gene, mostly linked to disease onset at a younger age), autosomal recessive, X-linked (mostly linked to lateonset cases), multi-factorial and co-dominant. Treatment Curative treatment is possible for localized prostate cancer. Men with strong positive family history should be offered risk assessment and regular follow-ups. Early detection is possible through PSA (prostate specific antigen) testing and DRE (digital rectal examination). In rare families where known mutations are segregating, genetic testing may be possible. Clinics Note Hereditary/familial prostate cancer is a heterogeneous disease entity with complex genetics. Phenotype and clinics The definition of hereditary prostate cancer (HPC) is based on the family history (pedigree). The suggested criteria include 1) nuclear family with three (or more) cases of prostate cancer, 2) prostate cancer in three successive generations, or 3) at least two men diagnosed with the disease before the age of 55 years. Familial aggregation of cases that don't fulfill the HPC criteria are defined as familial prostate cancer. The onset of HPC is on average 6 years earlier than of sporadic prostate cancer but the clinical course is otherwise no different. Prognosis Prognosis is more dependent on extent of the disease at diagnosis than on the genetic susceptibility. PSA testing is as efficient in HPC families as in the general population. Genes involved and proteins Note There is strong evidence from epidemiological and family studies in support of genetic predisposition to prostate cancer. Despite this, no major susceptibility gene has been identified. It is commonly accepted that predisposition may be mediated through multiple common low-to-moderate-penetrance risk alleles. Only few rare (high-risk) mutations in candidate genes have Neoplastic risk There is a greater risk of prostate cancer for brothers and sons of men with the disease. The relative risk of prostate cancer is about two-fold in first-degree relatives of affected men and the risk Atlas Genet Cytogenet Oncol Haematol. 2009; 13(6) 448 Hereditary prostate cancer Schleutker J Probably involved in tRNA maturation, by removing a 3'-trailer from precursor tRNA. Homology: Mouse, rat. Mutations Germinal: 4 mutations associated with prostate cancer susceptibility, altogether about 20 variants described. Two truncating nonsense mutations mutations have been found in HPC families. In addition, two common missense variants, Ser217Leu and Ala541Thr, have also been associated with familial prostate cancer susceptibility. been found in families fulfilling the HPC definition. Familial prostate cancer is likely a mixture of cases caused by dominant high-risk genes, risk-modulating genes, environmental risk factors and ageing. RNASEL Location 1q25 Note Ribonuclease L (2',5'-oligoisoadenylate synthetasedependent), encodes an antiviral, proapoptotic and interferon-activated RNase. DNA/RNA Description: 6 coding exons spanning 13,337 bases of genomic DNA, mRNA has a size of 4,166 kb. Protein Description: 741 amino acids, 83,533 Da. Expression: Highly expressed in spleen and thymus followed by prostate, testis, uterus, small intestine, colon and peripheral blood leukocytes. Localisation: Cytoplasm and mitochondrion. Function: Endoribonuclease, mediator of interferon action, which play a role in mediating resistance to virus infection and apoptosis. Possibly play a central role in the regulation of mRNA turnover. Homology: Mouse, rat. Mutations Germinal: About 20 mutations/variants described. Met1Ile, Glu265>Stop and Arg462Gln were the first identified risk alleles for HPC. Arg462Gln has three times reduced enzymatic activity. A founder 471delAAAG has been found in Ashkenazi Jews. Glu265>Stop and Asp/Asp genotype of codon 541 have been associated with familial prostate cancer risk in Finnish and Japanese populations, respectively. These mutations are often associated with early age of onset. MSR1 Location 8p22 DNA/RNA Note: Three isoforms. Isoform type 1 has a total length of 67,904; processed length of 1,356 and protein product length of 451. Isoform 2 has a total length of 53,475; processed length of 2,960 and mRNA product length of 2,960. Isoform 3 has a total length of 67,904; processed length of 1,167 and protein product length of 388. The isoforms type 1 and type 2 are functional receptors and are able to mediate the endocytosis of modified low density lipoproteins (LDLs). The isoform type 3 does not internalize modified LDL (acetyl-LDL) despite having the domain shown to mediate this function in the types 1 and 2 isoforms. It has an altered intracellular processing and is trapped within the endoplasmic reticulum, making it unable to perform endocytosis. Description: 9 (8) coding exons spanning 84.914 bases of genomic DNA, mRNA has a size of 1,167-3,761. Protein Note: Macrophage scavenger receptor types I and II. Description: I 451 amino acids, 49,762 Da; II 358 amino acids, 39,584 Da Expression: Widely expressed. Highly expressed in heart, placenta, liver, skeletal muscle, kidney, pancreas, testis and ovary. Weakly expressed in brain, lung, spleen, thymus, prostate, small intestine, colon and leukocytes. Localisation: Membrane; Single-pass type II membrane protein. Function: Membrane glycoproteins implicated in the pathologic deposition of cholesterol in arterial walls during atherogenesis. Two types of receptor subunits exist. These receptors mediate the endocytosis of a diverse group of macromolecules, including modified low density lipoproteins (LDL). Homology: Mouse, rat. Mutations Germinal: Truncating mutations originally found in African-American and European-American men. Arg293X truncating mutation results in a dominant negative mutant of the gene. ELAC2 Location 17p11.2 DNA/RNA Description: 24 coding exons spanning 25,658 bases of genomic DNA, mRNA has a size of 3,026. Protein Note: Zinc phosphodiesterase ELAC protein 2. Description: Protein product of 826 amino acids; 92,219 Da. Expression: Highly expressed in heart, placenta, liver, skeletal muscle, kidney, pancreas, testis and ovary. Weakly expressed in brain, lung, spleen, thymus, prostate, small intestine, colon and leukocytes. Localisation: Nucleus. Function: Zinc phosphodiesterase, which displays some tRNA 3'-processing endonuclease activity. Atlas Genet Cytogenet Oncol Haematol. 2009; 13(6) 449 Hereditary prostate cancer Schleutker J To be noted chromosome 1q42.2-43. Jun;62(6):1416-24 Note In addition to the three strong candidate susceptibility genes (RNASEL, ELAC2 and MSR1), a number of other loci have been identified in genome-wide genetic linkage studies using HPC families. These include for example 1p35-36 (CAPB), 1q42-43 (PCAP), 16q23, 17q22, 20q13 (HPC20) and Xq27-28 (HPCX). However, many of the reported loci have been hard to validate in other populations and therefore the results of the linkage analyses have remained disparate. More recently, using genome-wide SNP analyses, even more susceptibility loci have been localized, including repeatedly detected 3p, 8q24, 10q11, 11q13, 17q and Xp11. In addition, association with familial prostate cancer has been detected with mutations of CHEK2 (22q12.1), BRCA2 (13q12), CDKN1B (12p13.1-p12), PON1 (7q21.3), SRD5A2 (2p23) and PALB2 (16p12.1) although the results are not fully consistent in all populations and ethnic groups studied. Schaid DJ, McDonnell SK, Blute ML, Thibodeau SN. Evidence for autosomal dominant inheritance of prostate cancer. Am J Hum Genet. 1998 Jun;62(6):1425-38 J Hum Genet. 1998 Xu J, Meyers D, Freije D, Isaacs S, Wiley K, Nusskern D, Ewing C, Wilkens E, Bujnovszky P, Bova GS, Walsh P, Isaacs W, Schleutker J, Matikainen M, Tammela T, Visakorpi T, Kallioniemi OP, Berry R, Schaid D, French A, McDonnell S, Schroeder J, Blute M, Thibodeau S, Grönberg H, Emanuelsson M, Damber JE, Bergh A, Jonsson BA, Smith J, Bailey-Wilson J, Carpten J, Stephan D, Gillanders E, Amundson I, Kainu T, Freas-Lutz D, Baffoe-Bonnie A, Van Aucken A, Sood R, Collins F, Brownstein M, Trent J. Evidence for a prostate cancer susceptibility locus on the X chromosome. Nat Genet. 1998 Oct;20(2):175-9 Cerhan JR, Parker AS, Putnam SD, Chiu BC, Lynch CF, Cohen MB, Torner JC, Cantor KP. Family history and prostate cancer risk in a population-based cohort of Iowa men. Cancer Epidemiol Biomarkers Prev. 1999 Jan;8(1):53-60 Gibbs M, Stanford JL, McIndoe RA, Jarvik GP, Kolb S, Goode EL, Chakrabarti L, Schuster EF, Buckley VA, Miller EL, Brandzel S, Li S, Hood L, Ostrander EA. Evidence for a rare prostate cancer-susceptibility locus at chromosome 1p36. Am J Hum Genet. 1999 Mar;64(3):776-87 References Makridakis NM, Ross RK, Pike MC, Crocitto LE, Kolonel LN, Pearce CL, Henderson BE, Reichardt JK. Association of missense substitution in SRD5A2 gene with prostate cancer in African-American and Hispanic men in Los Angeles, USA. Lancet. 1999 Sep 18;354(9183):975-8 Carter BS, Beaty TH, Steinberg GD, Childs B, Walsh PC. Mendelian inheritance of familial prostate cancer. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3367-71 Hayes RB, Liff JM, Pottern LM, Greenberg RS, Schoenberg JB, Schwartz AG, Swanson GM, Silverman DT, Brown LM, Hoover RN. Prostate cancer risk in U.S. blacks and whites with a family history of cancer. Int J Cancer. 1995 Jan 27;60(3):3614 Berry R, Schaid DJ, Smith JR, French AJ, Schroeder JJ, McDonnell SK, Peterson BJ, Wang ZY, Carpten JD, Roberts SG, Tester DJ, Blute ML, Trent JM, Thibodeau SN. Linkage analyses at the chromosome 1 loci 1q24-25 (HPC1), 1q42.243 (PCAP), and 1p36 (CAPB) in families with hereditary prostate cancer. Am J Hum Genet. 2000 Feb;66(2):539-46 Monroe KR, Yu MC, Kolonel LN, Coetzee GA, Wilkens LR, Ross RK, Henderson BE. Evidence of an X-linked or recessive genetic component to prostate cancer risk. Nat Med. 1995 Aug;1(8):827-9 Berry R, Schroeder JJ, French AJ, McDonnell SK, Peterson BJ, Cunningham JM, Thibodeau SN, Schaid DJ. Evidence for a prostate cancer-susceptibility locus on chromosome 20. Am J Hum Genet. 2000 Jul;67(1):82-91 Narod SA, Dupont A, Cusan L, Diamond P, Gomez JL, Suburu R, Labrie F. The impact of family history on early detection of prostate cancer. Nat Med. 1995 Feb;1(2):99-101 Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K. Environmental and heritable factors in the causation of cancer-analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med. 2000 Jul 13;343(2):78-85 Smith JR, Freije D, Carpten JD, Grönberg H, Xu J, Isaacs SD, Brownstein MJ, Bova GS, Guo H, Bujnovszky P, Nusskern DR, Damber JE, Bergh A, Emanuelsson M, Kallioniemi OP, Walker-Daniels J, Bailey-Wilson JE, Beaty TH, Meyers DA, Walsh PC, Collins FS, Trent JM, Isaacs WB. Major susceptibility locus for prostate cancer on chromosome 1 suggested by a genome-wide search. Science. 1996 Nov 22;274(5291):1371-4 Schleutker J, Matikainen M, Smith J, Koivisto P, Baffoe-Bonnie A, Kainu T, Gillanders E, Sankila R, Pukkala E, Carpten J, Stephan D, Tammela T, Brownstein M, Bailey-Wilson J, Trent J, Kallioniemi OP. A genetic epidemiological study of hereditary prostate cancer (HPC) in Finland: frequent HPCX linkage in families with late-onset disease. Clin Cancer Res. 2000 Dec;6(12):4810-5 Grönberg H, Damber L, Damber JE, Iselius L. Segregation analysis of prostate cancer in Sweden: support for dominant inheritance. Am J Epidemiol. 1997 Oct 1;146(7):552-7 Cui J, Staples MP, Hopper JL, English DR, McCredie MR, Giles GG. Segregation analyses of 1,476 population-based Australian families affected by prostate cancer. Am J Hum Genet. 2001 May;68(5):1207-18 Grönberg H, Xu J, Smith JR, Carpten JD, Isaacs SD, Freije D, Bova GS, Danber JE, Bergh A, Walsh PC, Collins FS, Trent JM, Meyers DA, Isaacs WB. Early age at diagnosis in families providing evidence of linkage to the hereditary prostate cancer locus (HPC1) on chromosome 1. Cancer Res. 1997 Nov 1;57(21):4707-9 Matikaine MP, Pukkala E, Schleutker J, Tammela TL, Koivisto P, Sankila R, Kallioniemi OP. Relatives of prostate cancer patients have an increased risk of prostate and stomach cancers: a population-based, cancer registry study in Finland. Cancer Causes Control. 2001 Apr;12(3):223-30 Berthon P, Valeri A, Cohen-Akenine A, Drelon E, Paiss T, Wöhr G, Latil A, Millasseau P, Mellah I, Cohen N, Blanché H, Bellané-Chantelot C, Demenais F, Teillac P, Le Duc A, de Petriconi R, Hautmann R, Chumakov I, Bachner L, Maitland NJ, Lidereau R, Vogel W, Fournier G, Mangin P, Cussenot O. Predisposing gene for early-onset prostate cancer, localized on Atlas Genet Cytogenet Oncol Haematol. 2009; 13(6) Am Tavtigian SV, Simard J, Teng DH, Abtin V, Baumgard M, Beck A, Camp NJ, Carillo AR, Chen Y, Dayananth P, Desrochers M, Dumont M, Farnham JM, Frank D, Frye C, Ghaffari S, Gupte 450 Hereditary prostate cancer Schleutker J JS, Hu R, Iliev D, Janecki T, Kort EN, Laity KE, Leavitt A, Leblanc G, McArthur-Morrison J, Pederson A, Penn B, Peterson KT, Reid JE, Richards S, Schroeder M, Smith R, Snyder SC, Swedlund B, Swensen J, Thomas A, Tranchant M, Woodland AM, Labrie F, Skolnick MH, Neuhausen S, Rommens J, Cannon-Albright LA. A candidate prostate cancer susceptibility gene at chromosome 17p. Nat Genet. 2001 Feb;27(2):172-80 Schleutker J, Lehtimäki T, Salonen JT. New paraoxonase 1 polymorphism I102V and the risk of prostate cancer in Finnish men. J Natl Cancer Inst. 2003 Jun 4;95(11):812-8 Verhage BA, Baffoe-Bonnie AB, Baglietto L, Smith DS, BaileyWilson JE, Beaty TH, Catalona WJ, Kiemeney LA. Autosomal dominant inheritance of prostate cancer: a confirmatory study. Urology. 2001 Jan;57(1):97-101 Seppälä EH, Ikonen T, Mononen N, Autio V, Rökman A, Matikainen MP, Tammela TL, Schleutker J. CHEK2 variants associate with hereditary prostate cancer. Br J Cancer. 2003 Nov 17;89(10):1966-70 Baffoe-Bonnie AB, Kiemeney LA, Beaty TH, Bailey-Wilson JE, Schnell AH, Sigvaldason H, Olafsdóttir G, Tryggvadóttir L, Tulinius H. Segregation analysis of 389 Icelandic pedigrees with Breast and prostate cancer. Genet Epidemiol. 2002 Nov;23(4):349-63 Valeri A, Briollais L, Azzouzi R, Fournier G, Mangin P, Berthon P, Cussenot O, Demenais F. Segregation analysis of prostate cancer in France: evidence for autosomal dominant inheritance and residual brother-brother dependence. Ann Hum Genet. 2003 Mar;67(Pt 2):125-37 Carpten J, Nupponen N, Isaacs S, Sood R, Robbins C, Xu J, Faruque M, Moses T, Ewing C, Gillanders E, Hu P, Bujnovszky P, Makalowska I, Baffoe-Bonnie A, Faith D, Smith J, Stephan D, Wiley K, Brownstein M, Gildea D, Kelly B, Jenkins R, Hostetter G, Matikainen M, Schleutker J, Klinger K, Connors T, Xiang Y, Wang Z, De Marzo A, Papadopoulos N, Kallioniemi OP, Burk R, Meyers D, Grönberg H, Meltzer P, Silverman R, Bailey-Wilson J, Walsh P, Isaacs W, Trent J. Germline mutations in the ribonuclease L gene in families showing linkage with HPC1. Nat Genet. 2002 Feb;30(2):181-4 Chang BL, Zheng SL, Isaacs SD, Wiley KE, Turner A, Li G, Walsh PC, Meyers DA, Isaacs WB, Xu J. A polymorphism in the CDKN1B gene is associated with increased risk of hereditary prostate cancer. Cancer Res. 2004 Mar 15;64(6):1997-9 Nakazato H, Suzuki K, Matsui H, Ohtake N, Nakata S, Yamanaka H. Role of genetic polymorphisms of the RNASEL gene on familial prostate cancer risk in a Japanese population. Br J Cancer. 2003 Aug 18;89(4):691-6 Schaid DJ. The complex genetic epidemiology of prostate cancer. Hum Mol Genet. 2004 Apr 1;13 Spec No 1:R103-21 Baffoe-Bonnie AB, Smith JR, Stephan DA, Schleutker J, Carpten JD, Kainu T, Gillanders EM, Matikainen M, Teslovich TM, Tammela T, Sood R, Balshem AM, Scarborough SD, Xu J, Isaacs WB, Trent JM, Kallioniemi OP, Bailey-Wilson JE. A major locus for hereditary prostate cancer in Finland: localization by linkage disequilibrium of a haplotype in the HPCX region. Hum Genet. 2005 Aug;117(4):307-16 Gong G, Oakley-Girvan I, Wu AH, Kolonel LN, John EM, West DW, Felberg A, Gallagher RP, Whittemore AS. Segregation analysis of prostate cancer in 1,719 white, African-American and Asian-American families in the United States and Canada. Cancer Causes Control. 2002 Jun;13(5):471-82 Hemminki K, Chen B. Familial association of prostate cancer with other cancers in the Swedish Family-Cancer Database. Prostate. 2005 Oct 1;65(2):188-94 Rökman A, Ikonen T, Seppälä EH, Nupponen N, Autio V, Mononen N, Bailey-Wilson J, Trent J, Carpten J, Matikainen MP, Koivisto PA, Tammela TL, Kallioniemi OP, Schleutker J. Germline alterations of the RNASEL gene, a candidate HPC1 gene at 1q25, in patients and families with prostate cancer. Am J Hum Genet. 2002 May;70(5):1299-304 Orr-Urtreger A, Bar-Shira A, Bercovich D, Matarasso N, Rozovsky U, Rosner S, Soloviov S, Rennert G, Kadouri L, Hubert A, Rennert H, Matzkin H. RNASEL mutation screening and association study in Ashkenazi and non-Ashkenazi prostate cancer patients. Cancer Epidemiol Biomarkers Prev. 2006 Mar;15(3):474-9 Xu J, Zheng SL, Komiya A, Mychaleckyj JC, Isaacs SD, Hu JJ, Sterling D, Lange EM, Hawkins GA, Turner A, Ewing CM, Faith DA, Johnson JR, Suzuki H, Bujnovszky P, Wiley KE, DeMarzo AM, Bova GS, Chang B, Hall MC, McCullough DL, Partin AW, Kassabian VS, Carpten JD, Bailey-Wilson JE, Trent JM, Ohar J, Bleecker ER, Walsh PC, Isaacs WB, Meyers DA. Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk. Nat Genet. 2002 Oct;32(2):321-5 Bratt O. What should a urologist know about hereditary predisposition to prostate cancer? BJU Int. 2007 Apr;99(4):743-7; discussion 747-8 Camp NJ, Cannon-Albright LA, Farnham JM, Baffoe-Bonnie AB, George A, Powell I, Bailey-Wilson JE, Carpten JD, Giles GG, Hopper JL, Severi G, English DR, Foulkes WD, Maehle L, Moller P, Eeles R, Easton D, Badzioch MD, Whittemore AS, Oakley-Girvan I, Hsieh CL, Dimitrov L, Xu J, Stanford JL, Johanneson B, Deutsch K, McIntosh L, Ostrander EA, Wiley KE, Isaacs SD, Walsh PC, Thibodeau SN, McDonnell SK, Hebbring S, Schaid DJ, Lange EM, Cooney KA, Tammela TL, Schleutker J, Paiss T, Maier C, Grönberg H, Wiklund F, Emanuelsson M, Isaacs WB. Compelling evidence for a prostate cancer gene at 22q12.3 by the International Consortium for Prostate Cancer Genetics. Hum Mol Genet. 2007 Jun 1;16(11):1271-8 Conlon EM, Goode EL, Gibbs M, Stanford JL, Badzioch M, Janer M, Kolb S, Hood L, Ostrander EA, Jarvik GP, Wijsman EM. Oligogenic segregation analysis of hereditary prostate cancer pedigrees: evidence for multiple loci affecting age at onset. Int J Cancer. 2003 Jul 10;105(5):630-5 Dong X, Wang L, Taniguchi K, Wang X, Cunningham JM, McDonnell SK, Qian C, Marks AF, Slager SL, Peterson BJ, Smith DI, Cheville JC, Blute ML, Jacobsen SJ, Schaid DJ, Tindall DJ, Thibodeau SN, Liu W. Mutations in CHEK2 associated with prostate cancer risk. Am J Hum Genet. 2003 Feb;72(2):270-80 Erkko H, Xia B, Nikkilä J, Schleutker J, Syrjäkoski K, Mannermaa A, Kallioniemi A, Pylkäs K, Karppinen SM, Rapakko K, Miron A, Sheng Q, Li G, Mattila H, Bell DW, Haber DA, Grip M, Reiman M, Jukkola-Vuorinen A, Mustonen A, Kere J, Aaltonen LA, Kosma VM, Kataja V, Soini Y, Drapkin RI, Livingston DM, Winqvist R. A recurrent mutation in PALB2 in Finnish cancer families. Nature. 2007 Mar 15;446(7133):316-9 Edwards SM, Kote-Jarai Z, Meitz J, Hamoudi R, Hope Q, Osin P, Jackson R, Southgate C, Singh R, Falconer A, Dearnaley DP, Ardern-Jones A, Murkin A, Dowe A, Kelly J, Williams S, Oram R, Stevens M, Teare DM, Ponder BA, Gayther SA, Easton DF, Eeles RA. Two percent of men with early-onset prostate cancer harbor germline mutations in the BRCA2 gene. Am J Hum Genet. 2003 Jan;72(1):1-12 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, Marchesani M, Hakkarainen A, Tuomainen TP, Kaikkonen J, Pukkala E, Uimari P, Seppälä E, Matikainen M, Kallioniemi OP, Atlas Genet Cytogenet Oncol Haematol. 2009; 13(6) 451 Hereditary prostate cancer Schleutker J Stacey SN, Mouy M, Saemundsdottir J, Backman VM, Kristjansson K, Tres A, Partin AW, Albers-Akkers MT, GodinoIvan 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. Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24. Nat Genet. 2007 May;39(5):631-7 Gudmundsson J, Sulem P, Rafnar T, Bergthorsson JT, Manolescu A, Gudbjartsson D, Agnarsson BA, Sigurdsson A, Benediktsdottir KR, Blondal T, Jakobsdottir M, Stacey SN, Kostic J, Kristinsson KT, Birgisdottir B, Ghosh S, Magnusdottir DN, Thorlacius S, Thorleifsson G, Zheng SL, Sun J, Chang BL, Elmore JB, Breyer JP, McReynolds KM, Bradley KM, Yaspan BL, Wiklund F, Stattin P, Lindström S, Adami HO, McDonnell SK, Schaid DJ, Cunningham JM, Wang L, Cerhan JR, St Sauver JL, Isaacs SD, Wiley KE, Partin AW, Walsh PC, Polo S, Ruiz-Echarri M, Navarrete S, Fuertes F, Saez B, Godino J, Weijerman PC, Swinkels DW, Aben KK, Witjes JA, Suarez BK, Helfand BT, Frigge ML, Kristjansson K, Ober C, Jonsson E, Einarsson GV, Xu J, Gronberg H, Smith JR, Thibodeau SN, Isaacs WB, Catalona WJ, Mayordomo JI, Kiemeney LA, Barkardottir RB, Gulcher JR, Thorsteinsdottir U, Kong A, Stefansson K. Common sequence variants on 2p15 and Xp11.22 confer susceptibility to prostate cancer. Nat Genet. 2008 Mar;40(3):281-3 Pakkanen S, Baffoe-Bonnie AB, Matikainen MP, Koivisto PA, Tammela TL, Deshmukh S, Ou L, Bailey-Wilson JE, Schleutker J. Segregation analysis of 1,546 prostate cancer families in Finland shows recessive inheritance. Hum Genet. 2007 Apr;121(2):257-67 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. Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat Genet. 2007 May;39(5):645-9 Pearce CL, Van Den Berg DJ, Makridakis N, Reichardt JK, Ross RK, Pike MC, Kolonel LN, Henderson BE. No association between the SRD5A2 gene A49T missense variant and prostate cancer risk: lessons learned. Hum Mol Genet. 2008 Aug 15;17(16):2456-61 Thomas G, Jacobs KB, Yeager M, Kraft P, Wacholder S, Orr N, Yu K, Chatterjee N, Welch R, Hutchinson A, Crenshaw A, Cancel-Tassin G, Staats BJ, Wang Z, Gonzalez-Bosquet J, Fang J, Deng X, Berndt SI, Calle EE, Feigelson HS, Thun MJ, Rodriguez C, Albanes D, Virtamo J, Weinstein S, Schumacher FR, Giovannucci E, Willett WC, Cussenot O, Valeri A, Andriole GL, Crawford ED, Tucker M, Gerhard DS, Fraumeni JF Jr, Hoover R, Hayes RB, Hunter DJ, Chanock SJ. Multiple loci identified in a genome-wide association study of prostate cancer. Nat Genet. 2008 Mar;40(3):310-5 Eeles RA, Kote-Jarai Z, Giles GG, Olama AA, Guy M, Jugurnauth SK, Mulholland S, Leongamornlert DA, Edwards SM, Morrison J, Field HI, Southey MC, Severi G, Donovan JL, Hamdy FC, Dearnaley DP, Muir KR, Smith C, Bagnato M, Ardern-Jones AT, Hall AL, O'Brien LT, Gehr-Swain BN, Wilkinson RA, Cox A, Lewis S, Brown PM, Jhavar SG, Tymrakiewicz M, Lophatananon A, Bryant SL, Horwich A, Huddart RA, Khoo VS, Parker CC, Woodhouse CJ, Thompson A, Christmas T, Ogden C, Fisher C, Jamieson C, Cooper CS, English DR, Hopper JL, Neal DE, Easton DF. Multiple newly identified loci associated with prostate cancer susceptibility. Nat Genet. 2008 Mar;40(3):316-21 Atlas Genet Cytogenet Oncol Haematol. 2009; 13(6) This article should be referenced as such: Schleutker J. Hereditary prostate cancer. Atlas Cytogenet Oncol Haematol. 2009; 13(6):448-452. 452 Genet