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Prostate cancer, hereditary, 2(HPC2)

MedGen UID:
761328
•Concept ID:
C3539120
•
Neoplastic Process
Synonym: HPC2
 
Gene (location): ELAC2 (17p12)
 
Monarch Initiative: MONDO:0013872
OMIM®: 614731

Definition

Prostate cancer is a common disease that affects men, usually in middle age or later. In this disorder, certain cells in the prostate become abnormal, multiply without control or order, and form a tumor. The prostate is a gland that surrounds the male urethra and helps produce semen, the fluid that carries sperm.

Early prostate cancer usually does not cause pain, and most affected men exhibit no noticeable symptoms. Men are often diagnosed as the result of health screenings, such as a blood test for a substance called prostate specific antigen (PSA) or a medical exam called a digital rectal exam (DRE). As the tumor grows larger, signs and symptoms can include difficulty starting or stopping the flow of urine, a feeling of not being able to empty the bladder completely, blood in the urine or semen, or pain with ejaculation. However, these changes can also occur with many other genitourinary conditions. Having one or more of these symptoms does not necessarily mean that a man has prostate cancer.

The severity and outcome of prostate cancer varies widely. Early-stage prostate cancer can usually be treated successfully, and some older men have prostate tumors that grow so slowly that they may never cause health problems during their lifetime, even without treatment. In other men, however, the cancer is much more aggressive; in these cases, prostate cancer can be life-threatening.

Some cancerous tumors can invade surrounding tissue and spread to other parts of the body. Tumors that begin at one site and then spread to other areas of the body are called metastatic cancers. The signs and symptoms of metastatic cancer depend on where the disease has spread. If prostate cancer spreads, cancerous cells most often appear in the lymph nodes, bones, lungs, liver, or brain.

A small percentage of prostate cancers are hereditary and occur in families. These hereditary cancers are associated with inherited gene variants. Hereditary prostate cancers tend to develop earlier in life than non-inherited (sporadic) cases. [from MedlinePlus Genetics]

Professional guidelines

PubMed

NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2024.
Daly MB, Pal T, Maxwell KN, Churpek J, Kohlmann W, AlHilli Z, Arun B, Buys SS, Cheng H, Domchek SM, Friedman S, Giri V, Goggins M, Hagemann A, Hendrix A, Hutton ML, Karlan BY, Kassem N, Khan S, Khoury K, Kurian AW, Laronga C, Mak JS, Mansour J, McDonnell K, Menendez CS, Merajver SD, Norquist BS, Offit K, Rash D, Reiser G, Senter-Jamieson L, Shannon KM, Visvanathan K, Welborn J, Wick MJ, Wood M, Yurgelun MB, Dwyer MA, Darlow SD
J Natl Compr Canc Netw 2023 Oct;21(10):1000-1010. doi: 10.6004/jnccn.2023.0051. PMID: 37856201
Management of individuals with germline pathogenic/likely pathogenic variants in CHEK2: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG).
Hanson H, Astiazaran-Symonds E, Amendola LM, Balmaña J, Foulkes WD, James P, Klugman S, Ngeow J, Schmutzler R, Voian N, Wick MJ, Pal T, Tischkowitz M, Stewart DR; ACMG Professional Practices and Guidelines Committee. Electronic address: documents@acmg.net
Genet Med 2023 Oct;25(10):100870. Epub 2023 Jul 25 doi: 10.1016/j.gim.2023.100870. PMID: 37490054Free PMC Article
Genetic Counseling for Men with Prostate Cancer.
Hyatt C, McDougall C, Miller-Samuel S, Russo J
Urol Clin North Am 2021 Aug;48(3):323-337. Epub 2021 Jun 16 doi: 10.1016/j.ucl.2021.03.004. PMID: 34210488

Recent clinical studies

Therapy

BRCA1, BRCA2, and Associated Cancer Risks and Management for Male Patients: A Review.
Cheng HH, Shevach JW, Castro E, Couch FJ, Domchek SM, Eeles RA, Giri VN, Hall MJ, King MC, Lin DW, Loeb S, Morgan TM, Offit K, Pritchard CC, Schaeffer EM, Szymaniak BM, Vassy JL, Katona BW, Maxwell KN
JAMA Oncol 2024 Sep 1;10(9):1272-1281. doi: 10.1001/jamaoncol.2024.2185. PMID: 39052257
Molecular basis and therapeutic targets in prostate cancer: A comprehensive review.
Militaru FC, Militaru V, Crisan N, Bocsan IC, Udrea AA, Catana A, Kutasi E, Militaru MS
Biomol Biomed 2023 Sep 4;23(5):760-771. doi: 10.17305/bb.2023.8782. PMID: 37021836Free PMC Article
Preclinical In Vivo Validation of the RAD51 Test for Identification of Homologous Recombination-Deficient Tumors and Patient Stratification.
Pellegrino B, Herencia-Ropero A, Llop-Guevara A, Pedretti F, Moles-Fernández A, Viaplana C, Villacampa G, Guzmán M, Rodríguez O, Grueso J, Jiménez J, Arenas EJ, Degasperi A, Dias JML, Forment JV, O'Connor MJ, Déas O, Cairo S, Zhou Y, Musolino A, Caldas C, Nik-Zainal S, Clarke RB, Nuciforo P, Díez O, Serres-Créixams X, Peg V, Espinosa-Bravo M, Macarulla T, Oaknin A, Mateo J, Arribas J, Dienstmann R, Bellet M, Oliveira M, Saura C, Gutiérrez-Enríquez S, Balmaña J, Serra V
Cancer Res 2022 Apr 15;82(8):1646-1657. doi: 10.1158/0008-5472.CAN-21-2409. PMID: 35425960Free PMC Article
Hereditary prostate cancer - Primetime for genetic testing?
Heidegger I, Tsaur I, Borgmann H, Surcel C, Kretschmer A, Mathieu R, Visschere P, Valerio M, van den Bergh RCN, Ost P, Tilki D, Gandaglia G, Ploussard G; EAU-YAU Prostate Cancer Working Party
Cancer Treat Rev 2019 Dec;81:101927. Epub 2019 Nov 11 doi: 10.1016/j.ctrv.2019.101927. PMID: 31783313
DNA Repair in Prostate Cancer: Biology and Clinical Implications.
Mateo J, Boysen G, Barbieri CE, Bryant HE, Castro E, Nelson PS, Olmos D, Pritchard CC, Rubin MA, de Bono JS
Eur Urol 2017 Mar;71(3):417-425. Epub 2016 Aug 31 doi: 10.1016/j.eururo.2016.08.037. PMID: 27590317

Prognosis

Hereditary breast and ovarian cancer: from genes to molecular targeted therapies.
Ponti G, De Angelis C, Ponti R, Pongetti L, Losi L, Sticchi A, Tomasi A, Ozben T
Crit Rev Clin Lab Sci 2023 Dec;60(8):640-650. Epub 2023 Jul 16 doi: 10.1080/10408363.2023.2234488. PMID: 37455374
Hereditary Prostate Cancer: Genes Related, Target Therapy and Prevention.
Vietri MT, D'Elia G, Caliendo G, Resse M, Casamassimi A, Passariello L, Albanese L, Cioffi M, Molinari AM
Int J Mol Sci 2021 Apr 4;22(7) doi: 10.3390/ijms22073753. PMID: 33916521Free PMC Article
Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database.
Dominguez-Valentin M, Sampson JR, Seppälä TT, Ten Broeke SW, Plazzer JP, Nakken S, Engel C, Aretz S, Jenkins MA, Sunde L, Bernstein I, Capella G, Balaguer F, Thomas H, Evans DG, Burn J, Greenblatt M, Hovig E, de Vos Tot Nederveen Cappel WH, Sijmons RH, Bertario L, Tibiletti MG, Cavestro GM, Lindblom A, Della Valle A, Lopez-Köstner F, Gluck N, Katz LH, Heinimann K, Vaccaro CA, Büttner R, Görgens H, Holinski-Feder E, Morak M, Holzapfel S, Hüneburg R, Knebel Doeberitz MV, Loeffler M, Rahner N, Schackert HK, Steinke-Lange V, Schmiegel W, Vangala D, Pylvänäinen K, Renkonen-Sinisalo L, Hopper JL, Win AK, Haile RW, Lindor NM, Gallinger S, Le Marchand L, Newcomb PA, Figueiredo JC, Thibodeau SN, Wadt K, Therkildsen C, Okkels H, Ketabi Z, Moreira L, Sánchez A, Serra-Burriel M, Pineda M, Navarro M, Blanco I, Green K, Lalloo F, Crosbie EJ, Hill J, Denton OG, Frayling IM, Rødland EA, Vasen H, Mints M, Neffa F, Esperon P, Alvarez K, Kariv R, Rosner G, Pinero TA, Gonzalez ML, Kalfayan P, Tjandra D, Winship IM, Macrae F, Möslein G, Mecklin JP, Nielsen M, Møller P
Genet Med 2020 Jan;22(1):15-25. Epub 2019 Jul 24 doi: 10.1038/s41436-019-0596-9. PMID: 31337882Free PMC Article
Microsatellite Instability Is Associated With the Presence of Lynch Syndrome Pan-Cancer.
Latham A, Srinivasan P, Kemel Y, Shia J, Bandlamudi C, Mandelker D, Middha S, Hechtman J, Zehir A, Dubard-Gault M, Tran C, Stewart C, Sheehan M, Penson A, DeLair D, Yaeger R, Vijai J, Mukherjee S, Galle J, Dickson MA, Janjigian Y, O'Reilly EM, Segal N, Saltz LB, Reidy-Lagunes D, Varghese AM, Bajorin D, Carlo MI, Cadoo K, Walsh MF, Weiser M, Aguilar JG, Klimstra DS, Diaz LA Jr, Baselga J, Zhang L, Ladanyi M, Hyman DM, Solit DB, Robson ME, Taylor BS, Offit K, Berger MF, Stadler ZK
J Clin Oncol 2019 Feb 1;37(4):286-295. Epub 2018 Oct 30 doi: 10.1200/JCO.18.00283. PMID: 30376427Free PMC Article
Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.
Schumacher FR, Al Olama AA, Berndt SI, Benlloch S, Ahmed M, Saunders EJ, Dadaev T, Leongamornlert D, Anokian E, Cieza-Borrella C, Goh C, Brook MN, Sheng X, Fachal L, Dennis J, Tyrer J, Muir K, Lophatananon A, Stevens VL, Gapstur SM, Carter BD, Tangen CM, Goodman PJ, Thompson IM Jr, Batra J, Chambers S, Moya L, Clements J, Horvath L, Tilley W, Risbridger GP, Gronberg H, Aly M, Nordström T, Pharoah P, Pashayan N, Schleutker J, Tammela TLJ, Sipeky C, Auvinen A, Albanes D, Weinstein S, Wolk A, Håkansson N, West CML, Dunning AM, Burnet N, Mucci LA, Giovannucci E, Andriole GL, Cussenot O, Cancel-Tassin G, Koutros S, Beane Freeman LE, Sorensen KD, Orntoft TF, Borre M, Maehle L, Grindedal EM, Neal DE, Donovan JL, Hamdy FC, Martin RM, Travis RC, Key TJ, Hamilton RJ, Fleshner NE, Finelli A, Ingles SA, Stern MC, Rosenstein BS, Kerns SL, Ostrer H, Lu YJ, Zhang HW, Feng N, Mao X, Guo X, Wang G, Sun Z, Giles GG, Southey MC, MacInnis RJ, FitzGerald LM, Kibel AS, Drake BF, Vega A, Gómez-Caamaño A, Szulkin R, Eklund M, Kogevinas M, Llorca J, Castaño-Vinyals G, Penney KL, Stampfer M, Park JY, Sellers TA, Lin HY, Stanford JL, Cybulski C, Wokolorczyk D, Lubinski J, Ostrander EA, Geybels MS, Nordestgaard BG, Nielsen SF, Weischer M, Bisbjerg R, Røder MA, Iversen P, Brenner H, Cuk K, Holleczek B, Maier C, Luedeke M, Schnoeller T, Kim J, Logothetis CJ, John EM, Teixeira MR, Paulo P, Cardoso M, Neuhausen SL, Steele L, Ding YC, De Ruyck K, De Meerleer G, Ost P, Razack A, Lim J, Teo SH, Lin DW, Newcomb LF, Lessel D, Gamulin M, Kulis T, Kaneva R, Usmani N, Singhal S, Slavov C, Mitev V, Parliament M, Claessens F, Joniau S, Van den Broeck T, Larkin S, Townsend PA, Aukim-Hastie C, Gago-Dominguez M, Castelao JE, Martinez ME, Roobol MJ, Jenster G, van Schaik RHN, Menegaux F, Truong T, Koudou YA, Xu J, Khaw KT, Cannon-Albright L, Pandha H, Michael A, Thibodeau SN, McDonnell SK, Schaid DJ, Lindstrom S, Turman C, Ma J, Hunter DJ, Riboli E, Siddiq A, Canzian F, Kolonel LN, Le Marchand L, Hoover RN, Machiela MJ, Cui Z, Kraft P, Amos CI, Conti DV, Easton DF, Wiklund F, Chanock SJ, Henderson BE, Kote-Jarai Z, Haiman CA, Eeles RA; Profile Study; Australian Prostate Cancer BioResource (APCB); IMPACT Study; Canary PASS Investigators; Breast and Prostate Cancer Cohort Consortium (BPC3); PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium; Cancer of the Prostate in Sweden (CAPS); Prostate Cancer Genome-wide Association Study of Uncommon Susceptibility Loci (PEGASUS); Genetic Associations and Mechanisms in Oncology (GAME-ON)/Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) Consortium
Nat Genet 2018 Jul;50(7):928-936. Epub 2018 Jun 11 doi: 10.1038/s41588-018-0142-8. PMID: 29892016Free PMC Article

Clinical prediction guides

Hereditary breast and ovarian cancer: from genes to molecular targeted therapies.
Ponti G, De Angelis C, Ponti R, Pongetti L, Losi L, Sticchi A, Tomasi A, Ozben T
Crit Rev Clin Lab Sci 2023 Dec;60(8):640-650. Epub 2023 Jul 16 doi: 10.1080/10408363.2023.2234488. PMID: 37455374
Hereditary Prostate Cancer: Genes Related, Target Therapy and Prevention.
Vietri MT, D'Elia G, Caliendo G, Resse M, Casamassimi A, Passariello L, Albanese L, Cioffi M, Molinari AM
Int J Mol Sci 2021 Apr 4;22(7) doi: 10.3390/ijms22073753. PMID: 33916521Free PMC Article
Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database.
Dominguez-Valentin M, Sampson JR, Seppälä TT, Ten Broeke SW, Plazzer JP, Nakken S, Engel C, Aretz S, Jenkins MA, Sunde L, Bernstein I, Capella G, Balaguer F, Thomas H, Evans DG, Burn J, Greenblatt M, Hovig E, de Vos Tot Nederveen Cappel WH, Sijmons RH, Bertario L, Tibiletti MG, Cavestro GM, Lindblom A, Della Valle A, Lopez-Köstner F, Gluck N, Katz LH, Heinimann K, Vaccaro CA, Büttner R, Görgens H, Holinski-Feder E, Morak M, Holzapfel S, Hüneburg R, Knebel Doeberitz MV, Loeffler M, Rahner N, Schackert HK, Steinke-Lange V, Schmiegel W, Vangala D, Pylvänäinen K, Renkonen-Sinisalo L, Hopper JL, Win AK, Haile RW, Lindor NM, Gallinger S, Le Marchand L, Newcomb PA, Figueiredo JC, Thibodeau SN, Wadt K, Therkildsen C, Okkels H, Ketabi Z, Moreira L, Sánchez A, Serra-Burriel M, Pineda M, Navarro M, Blanco I, Green K, Lalloo F, Crosbie EJ, Hill J, Denton OG, Frayling IM, Rødland EA, Vasen H, Mints M, Neffa F, Esperon P, Alvarez K, Kariv R, Rosner G, Pinero TA, Gonzalez ML, Kalfayan P, Tjandra D, Winship IM, Macrae F, Möslein G, Mecklin JP, Nielsen M, Møller P
Genet Med 2020 Jan;22(1):15-25. Epub 2019 Jul 24 doi: 10.1038/s41436-019-0596-9. PMID: 31337882Free PMC Article
Microsatellite Instability Is Associated With the Presence of Lynch Syndrome Pan-Cancer.
Latham A, Srinivasan P, Kemel Y, Shia J, Bandlamudi C, Mandelker D, Middha S, Hechtman J, Zehir A, Dubard-Gault M, Tran C, Stewart C, Sheehan M, Penson A, DeLair D, Yaeger R, Vijai J, Mukherjee S, Galle J, Dickson MA, Janjigian Y, O'Reilly EM, Segal N, Saltz LB, Reidy-Lagunes D, Varghese AM, Bajorin D, Carlo MI, Cadoo K, Walsh MF, Weiser M, Aguilar JG, Klimstra DS, Diaz LA Jr, Baselga J, Zhang L, Ladanyi M, Hyman DM, Solit DB, Robson ME, Taylor BS, Offit K, Berger MF, Stadler ZK
J Clin Oncol 2019 Feb 1;37(4):286-295. Epub 2018 Oct 30 doi: 10.1200/JCO.18.00283. PMID: 30376427Free PMC Article
Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.
Schumacher FR, Al Olama AA, Berndt SI, Benlloch S, Ahmed M, Saunders EJ, Dadaev T, Leongamornlert D, Anokian E, Cieza-Borrella C, Goh C, Brook MN, Sheng X, Fachal L, Dennis J, Tyrer J, Muir K, Lophatananon A, Stevens VL, Gapstur SM, Carter BD, Tangen CM, Goodman PJ, Thompson IM Jr, Batra J, Chambers S, Moya L, Clements J, Horvath L, Tilley W, Risbridger GP, Gronberg H, Aly M, Nordström T, Pharoah P, Pashayan N, Schleutker J, Tammela TLJ, Sipeky C, Auvinen A, Albanes D, Weinstein S, Wolk A, Håkansson N, West CML, Dunning AM, Burnet N, Mucci LA, Giovannucci E, Andriole GL, Cussenot O, Cancel-Tassin G, Koutros S, Beane Freeman LE, Sorensen KD, Orntoft TF, Borre M, Maehle L, Grindedal EM, Neal DE, Donovan JL, Hamdy FC, Martin RM, Travis RC, Key TJ, Hamilton RJ, Fleshner NE, Finelli A, Ingles SA, Stern MC, Rosenstein BS, Kerns SL, Ostrer H, Lu YJ, Zhang HW, Feng N, Mao X, Guo X, Wang G, Sun Z, Giles GG, Southey MC, MacInnis RJ, FitzGerald LM, Kibel AS, Drake BF, Vega A, Gómez-Caamaño A, Szulkin R, Eklund M, Kogevinas M, Llorca J, Castaño-Vinyals G, Penney KL, Stampfer M, Park JY, Sellers TA, Lin HY, Stanford JL, Cybulski C, Wokolorczyk D, Lubinski J, Ostrander EA, Geybels MS, Nordestgaard BG, Nielsen SF, Weischer M, Bisbjerg R, Røder MA, Iversen P, Brenner H, Cuk K, Holleczek B, Maier C, Luedeke M, Schnoeller T, Kim J, Logothetis CJ, John EM, Teixeira MR, Paulo P, Cardoso M, Neuhausen SL, Steele L, Ding YC, De Ruyck K, De Meerleer G, Ost P, Razack A, Lim J, Teo SH, Lin DW, Newcomb LF, Lessel D, Gamulin M, Kulis T, Kaneva R, Usmani N, Singhal S, Slavov C, Mitev V, Parliament M, Claessens F, Joniau S, Van den Broeck T, Larkin S, Townsend PA, Aukim-Hastie C, Gago-Dominguez M, Castelao JE, Martinez ME, Roobol MJ, Jenster G, van Schaik RHN, Menegaux F, Truong T, Koudou YA, Xu J, Khaw KT, Cannon-Albright L, Pandha H, Michael A, Thibodeau SN, McDonnell SK, Schaid DJ, Lindstrom S, Turman C, Ma J, Hunter DJ, Riboli E, Siddiq A, Canzian F, Kolonel LN, Le Marchand L, Hoover RN, Machiela MJ, Cui Z, Kraft P, Amos CI, Conti DV, Easton DF, Wiklund F, Chanock SJ, Henderson BE, Kote-Jarai Z, Haiman CA, Eeles RA; Profile Study; Australian Prostate Cancer BioResource (APCB); IMPACT Study; Canary PASS Investigators; Breast and Prostate Cancer Cohort Consortium (BPC3); PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium; Cancer of the Prostate in Sweden (CAPS); Prostate Cancer Genome-wide Association Study of Uncommon Susceptibility Loci (PEGASUS); Genetic Associations and Mechanisms in Oncology (GAME-ON)/Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) Consortium
Nat Genet 2018 Jul;50(7):928-936. Epub 2018 Jun 11 doi: 10.1038/s41588-018-0142-8. PMID: 29892016Free PMC Article

Recent systematic reviews

Germline mutations in prostate cancer: a systematic review of the evidence for personalized medicine.
Marino F, Totaro A, Gandi C, Bientinesi R, Moretto S, Gavi F, Pierconti F, Iacovelli R, Bassi P, Sacco E
Prostate Cancer Prostatic Dis 2023 Dec;26(4):655-664. Epub 2022 Nov 24 doi: 10.1038/s41391-022-00609-3. PMID: 36434163
BRCA Genes and Related Cancers: A Meta-Analysis from Epidemiological Cohort Studies.
Lee YC, Lee YL, Li CY
Medicina (Kaunas) 2021 Aug 30;57(9) doi: 10.3390/medicina57090905. PMID: 34577828Free PMC Article
Homeobox B13 G84E Mutation and Prostate Cancer Risk.
Nyberg T, Govindasami K, Leslie G, Dadaev T, Bancroft E, Ni Raghallaigh H, Brook MN, Hussain N, Keating D, Lee A, McMahon R, Morgan A, Mullen A, Osborne A, Rageevakumar R; UK Genetic Prostate Cancer Study Collaborators, Kote-Jarai Z, Eeles R, Antoniou AC
Eur Urol 2019 May;75(5):834-845. Epub 2018 Dec 8 doi: 10.1016/j.eururo.2018.11.015. PMID: 30527799Free PMC Article
Risk of prostate cancer in Lynch syndrome: a systematic review and meta-analysis.
Ryan S, Jenkins MA, Win AK
Cancer Epidemiol Biomarkers Prev 2014 Mar;23(3):437-49. Epub 2014 Jan 14 doi: 10.1158/1055-9965.EPI-13-1165. PMID: 24425144
A systematic review of replication studies of prostate cancer susceptibility genetic variants in high-risk men originally identified from genome-wide association studies.
Ishak MB, Giri VN
Cancer Epidemiol Biomarkers Prev 2011 Aug;20(8):1599-610. Epub 2011 Jun 29 doi: 10.1158/1055-9965.EPI-11-0312. PMID: 21715604

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