Prostate cancer is the most common malignancy found in men, incidence is highest among American Blacks and lowest in East Asian populations. Prostate specific Antigen (PSA) is an important marker in the diagnosis and monitoring of
prostate cancer, and the percentage free PSA has been shown to have prognostic significance in some studies.
Androgens, which exert their effects via the androgen receptor (AR), are essential for the normal prostate. They are also required by prostate cancer cells. Therefore, androgen ablation and antiandrogen therapy are important in the
treatment of the disease, though most patients go on to develop androgen-independent prostate cancer. Androgen receptor mutations are observed in late stage prostate cancer.
Caveolin-1 is overexpressed in about a quarter of human prostate cancers (Yang, 1999) . Caveolin expression is thought to induce androgen sensitivity in androgen-insensitive prostate cancer cells.
Mutations in a diverse range of other genes have been implicated in prostate cancer including PTEN, KAI1, SRD5A2, and IL6. Most of these relate to disease
progression.
Hereditary prostate cancer accounts for about 9% of cases. A prostate cancer susceptibility locus (HPC1) on chromosome 1q24-25 was identified by Smith (1996). However, subsequent studies suggest that
mutations in HPC1 are uncommon and are restricted to people with early onset disease. A second gene (HPC2 on chromosome 1q42.2-q43 was proposed by Berthon (1998), though again subsequent linkage studies indicate this gene could only
account for a small proportion of cases. Other specific gene(s) associated with hereditary prostate cancer have yet to be identified.
Jenster G. The role of the androgen receptor in the development and progression of prostate cancer. Semin Oncol. 1999; 26(4):407-21. [Review] Related articles (PubMed)
Daliani D, Papandreou CN. Markers of androgen-independent progression of prostatic carcinoma. Semin Oncol. 1999; 26(4):399-406. [Review] Related articles (PubMed)
Bangma CH, et al. Metastasis-related genes in prostate cancer. Semin Oncol. 1999; 26(4):422-7. [Review] Related articles (PubMed)
Brothman AR, et al. Chromosomal clues to the development of prostate tumors. Prostate 1999 Mar 1;38(4):303-12 Related articles (PubMed)
Medline Search: prostate cancer AND genetics (PubMed)
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 Familial Prostate Cancer
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Hereditary prostate cancer accounts for about 9% of cases. A prostate cancer susceptibility locus (HPC1) on chromosome 1q24-25 was idenified by Smith (1996). However, McIndoe (1997) found no evidence of HPC1 mutation in 49 high-risk
families. Also in a study of "small" families [3-5 affected members], Dunsmuir (1998) found less than 8% of cases had allelic loss in HPC1. Other studies suggest that mutations in HPC1 are uncommon and are restricted to people with early onset disease.
Other candidate genes have been proposed. HPCX at chromosome Xq27-28 was identified by a large international linkage study of 360 families (Xu, 1998). Another locus - HPC2 (PCAP) on chromosome 1q42.2-q43
was proposed by Berthon (1998), though a subsequent linkage study (Gibbs, 1999) indicated this gene could only account for a small proportion of cases.
Other specific gene(s) associated with familial prostate cancer have yet to be identified.
Gibbs M, et al. Analysis of Chromosome 1q42.2-43 in 152 Families with High Risk of Prostate Cancer. Am J Hum Genet 1999; 64(4):1087-1095 Related articles (PubMed)
Berthon P, et al. Predisposing gene for early-onset prostate cancer, localized on chromosome 1q42.2-43. Am J Hum Genet 1998; 62(6):1416-24 Related articles (PubMed)
Ekman P Genetic and environmental factors in prostate cancer genesis: identifying high-risk cohorts. [Review] Eur Urol 1999;35(5-6):362-9 Related articles (PubMed)
Dunsmuir WD, et al. Allelic imbalance in familial and sporadic prostate cancer at the putative human prostate cancer susceptibility locus, HPC1. CRC/BPG UK Familial Prostate Cancer Study Collaborators. Cancer Research Campaign/British Prostate Group. Br J Cancer 1998;78(11):1430-3 Related articles (PubMed)
Gronberg H, et al. In Swedish families with hereditary prostate cancer, linkage to the HPC1 locus on chromosome 1q24-25 is restricted to families with early-onset prostate cancer. Am J Hum Genet. 1999;65(1):134-40 Related articles (PubMed)
McIndoe RA, et al. Linkage analysis of 49 high-risk families does not support a common familial prostate cancer-susceptibility gene at 1q24-25. Am J Hum Genet 1997; 61(2):347-53 Related articles (PubMed)
Carter BS, et al. Mendelian inheritance of familial prostate cancer. Proc Natl Acad Sci USA 1992; 89(8):3367-71 Related articles (PubMed)
Medline Search: familial prostate cancer (PubMed)
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| del(8p22) in Prostate Cancer
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Arbieva ZH, et al. High-Resolution Physical Map and Transcript Identification of a Prostate Cancer Deletion Interval on 8p22. Genome Res 2000;10(2):244-257 Related articles (PubMed)
Bova GS, et al. Physical mapping of chromosome 8p22 markers and their homozygous deletion in a metastatic prostate cancer. Genomics. 1996; 35(1):46-54. Related articles (PubMed)
Medline Search: prostate cancer AND chromosome 8 (PubMed)
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 Prostate Cancer Genetics
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Chromosme 8
| Chromosome Y Abnormalities in Prostate Cancer
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Perinchery G, et al. Deletion of Y-chromosome specific genes in human prostate cancer. J Urol 2000;163(4):1339-42 Related articles (PubMed)
Lau YF, Zhang J Expression analysis of thirty one Y chromosome genes in human prostate cancer. Mol Carcinog 2000;27(4):308-21 Related articles (PubMed)
Medline Search: prostate cancer AND chromosome Y (PubMed)
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Prostate Cancer Genetics
Prostate Cancer : Clinical and Epidemiological Information
Chromosme Y
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