Prostate cancer

Prostate cancer constitutes a major health problem in Western countries. It is the most frequently diagnosed cancer among men and the second leading cause of male cancer deaths. The identification of key molecular alterations in prostate-cancer cells implicates carcinogen defenses (GSTP1), growth-factor-signaling pathways (NKX3.1, PTEN, and p27), and androgens (AR) as critical determinants of the phenotype of prostate-cancer cells. Glutathione S-transferases (GSTP1) are detoxifying enzymes. Cells of prostatic intraepithelial neoplasia, devoid of GSTP1, undergo genomic damage mediated by carcinogens. NKX3.1, PTEN, and p27 regulate the growth and survival of prostate cells in the normal prostate. Inadequate levels of PTEN and NKX3.1 lead to a reduction in p27 levels and to increased proliferation and decreased apoptosis. Androgen receptor (AR) is a transcription factor that is normally activated by its androgen ligand. During androgen withdrawal therapy, the AR signal transduction pathway also could be activated by amplification of the AR gene, by AR gene mutations, or by altered activity of AR coactivators. Through these mechanisms, tumor cells lead to the emergence of androgen-independent prostate cancer.

Cancer

AR (amplification, mutation) [HSA:367] [KO:K08557]
CDKN1B (allelic loss) [HSA:1027] [KO:K06624]
NKX3.1 (allelic loss) (decreased expression) [HSA:4824] [KO:K09348]
PTEN (allelic loss) [HSA:5728] [KO:K01110]
GSTP1 (hypermethylation) [HSA:2950] [KO:K00799]
TMPRSS2-ERG (translocation) [HSA:2078] [KO:K09435]
TMPRSS2-ETV1 (translocation) [HSA:2115] [KO:K09431]
TMPRSS2-ETV4 (translocation) [HSA:2118] [KO:K15592]
TMPRSS2-ETV5 (translocation) [HSA:2119] [KO:K15593]
SLC45A3-ETV1 (translocation) [HSA:2115] [KO:K09431]
SLC45A3-ELK4 (translocation) [HSA:2005] [KO:K04376]
DDX5-ETV4 (translocation) [HSA:2118] [KO:K15592]

Cadmium and cadmium compounds [CPD:C01413]
Chimney sweeping

Estradiol valerate [DR:D01413]
Docetaxel [DR:D07866]
Docetaxel [DR:D02165]
Cabazitaxel acetonate [DR:D10452]
Estramustine phosphate sodium [DR:D02398]
Leuprolide acetate [DR:D00989]
Goserelin acetate [DR:D00573]
Triptorelin pamoate [DR:D06248]
Histrelin acetate [DR:D02116]
Flutamide [DR:D00586]
Nilutamide [DR:D00965]
Bicalutamide [DR:D00961]
Enzalutamide [DR:D10218]
Apalutamide [DR:D11040]
Degarelix acetate [DR:D09400]
Abiraterone acetate [DR:D09701]
Radium-223 dichloride [DR:D10398]
Estrogens, esterified [DR:D04071]

ICD-O: 8140/3, Tumor type: Adenocarcinoma (acinar)
ICD-O: 8148/2, Tumor type: Prostatic intraepithelial neoplasia, glade III (PIN III)

PMID:12878745 (gene, tumor type)

Nelson WG, De Marzo AM, Isaacs WB.

Prostate cancer.

N Engl J Med 349:366-81 (2003)
DOI:10.1056/NEJMra021562

PMID:17384581 (gene, tumor type)

De Marzo AM, Platz EA, Sutcliffe S, Xu J, Gronberg H, Drake CG, Nakai Y, Isaacs WB, Nelson WG.

Inflammation in prostate carcinogenesis.

Nat Rev Cancer 7:256-69 (2007)
DOI:10.1038/nrc2090

PMID:11018010 (tumor type)

Abate-Shen C, Shen MM.

Molecular genetics of prostate cancer.

Genes Dev 14:2410-34 (2000)
DOI:10.1101/gad.819500

PMID:15149739

Porkka KP, Visakorpi T.

Molecular mechanisms of prostate cancer.

Eur Urol 45:683-91 (2004)
DOI:10.1016/j.eururo.2004.01.012

PMID:19406209

Brenner JC, Chinnaiyan AM

Translocations in epithelial cancers.

Biochim Biophys Acta 1796:201-15 (2009)
DOI:10.1016/j.bbcan.2009.04.005

PMID:15660110 (carcinogen)

Luch A.

Nature and nurture - lessons from chemical carcinogenesis.

Nat Rev Cancer 5:113-25 (2005)
DOI:10.1038/nrc1546

PMID:9498904 (carcinogen)

Boffetta P, Jourenkova N, Gustavsson P.

Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons.

Cancer Causes Control 8:444-72 (1997)