Prostate Cancer: Epidemiology and Pathogenesis: Difference between revisions
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== Pathogenesis == | == Pathogenesis == | ||
* '''<span style="color:#ff0000">Risk factors (5 ( | * '''<span style="color:#ff0000">Risk factors (5 (only hereditary risk factors mentioned in 2023 AUA Early Detection of Prostate Cancer Guidelines):</span>''' | ||
*# '''<span style="color:#ff0000"> | *# '''<span style="color:#ff0000">Hereditary (3):</span>''' | ||
*# | *##'''<span style="color:#ff0000">Germline mutations</span>''' | ||
*#* | *##* '''<span style="color:#ff0000">Frequency of germline mutations in genes mediating DNA-repair processes by population:[https://www.nejm.org/doi/full/10.1056/NEJMoa1603144]</span>''' | ||
*#* | *##**'''Metastatic prostate cancer: 12%''' | ||
*#''' | *##**'''Localized prostate cancer: 5%''' | ||
*#* ''' | *##**'''General population: 2.7%''' | ||
*#** | *##*'''<span style="color:#ff0000">BReast CAncer Genes (BRCA)</span>''' | ||
*#** | *##** '''BRCA1 and BRCA2 variants have increased risks of both prostate cancer incidence and progression.''' | ||
*#**''' | *##*** More likely to present with higher grade, locally advanced, and metastatic disease, and have worse cancer-specific survival and metastasis-free survival after prostatectomy | ||
*#*''' | *##*** 2-6x increased lifetime risk | ||
*#** '''BRCA1 | *##*** Increased risk of metastasis and prostate cancer-specific mortality[https://pubmed.ncbi.nlm.nih.gov/25454609/] | ||
*#*** | *##*** '''Stronger association between BRCA2, compared to BRCA1, with both incidence and aggressive cancer''' | ||
*#* | *##*** '''Systematic PSA screening is indicated''' | ||
*# | *##** '''<span style="color:#ff0000">Hereditary breast and ovarian cancer syndrome</span>''' | ||
*#** | *##*** '''Most commonly associated with mutations in either the BRCA1 or BRCA2 gene''' | ||
*##*** '''<span style="color:#ff0000">Associated cancers (5):[https://www.ncbi.nlm.nih.gov/books/NBK1247/]</span>''' | |||
*#** '''<span style="color:#ff0000"> | *##**# '''<span style="color:#ff0000">Breast (male and female)</span>''' | ||
*#** | *##**# '''<span style="color:#ff0000">Ovarian</span>''' | ||
*#** | *##**# '''<span style="color:#ff0000">Prostate</span>''' | ||
*#* | *##**# '''<span style="color:#ff0000">Pancreatic</span>''' | ||
*#** | *##**# '''<span style="color:#ff0000">Melanoma</span>''' | ||
*#** | *##* '''<span style="color:#ff0000">Lynch syndrome</span>[https://cebp.aacrjournals.org/content/23/3/437]''' | ||
*#** | *##** '''Also known as hereditary non-polyposis colorectal cancer (HNPCC)''' | ||
*##** '''Due to inherited mutations in genes (MLH1, MSH2, MSH6, PMS2, and EPCAM) that affect DNA mismatch repair''' | |||
*#* '''<span style="color:#ff0000"> | *##** '''<span style="color:#ff0000">Associated cancers (10)</span>[https://www.ncbi.nlm.nih.gov/books/NBK431096/]''' | ||
*#** ''' | *##**#'''<span style="color:#ff0000">Colorectal</span>''' | ||
*#** ''' | *##**#'''<span style="color:#ff0000">Gastric</span>''' | ||
*##**#'''<span style="color:#ff0000">Ovarian</span>''' | |||
*#**#'''<span style="color:#ff0000"> | *##**#'''<span style="color:#ff0000">Small bowel</span>''' | ||
*#**#'''<span style="color:#ff0000"> | *##**# '''<span style="color:#ff0000">Upper tract urothelial carcinoma</span>''' | ||
*#**#'''<span style="color:#ff0000"> | *##**#'''<span style="color:#ff0000">Biliary tract</span>''' | ||
*#**#'''<span style="color:#ff0000"> | *##**# '''<span style="color:#ff0000">Pancreatic</span>''' | ||
*#**# '''<span style="color:#ff0000"> | *##**# '''<span style="color:#ff0000">Brain cancers (glioblastoma)</span>''' | ||
*#* | *##**#'''<span style="color:#ff0000">Sebaceous gland adenomas</span>''' | ||
*#** | *##**#'''<span style="color:#ff0000">Keratoacanthomas</span>''' | ||
*#** | *##* '''<span style="color:#ff0000">Other mutations</span>''' | ||
*# | *##** '''<span style="color:#ff0000">ATM, MLH1, MSH2, MSH6, PMS2, HOXB13, NBS1, and CHEK2</span>''' | ||
*#* | *##*** '''<span style="color:#ff0000">These mutations need further study to evaluate their role in prostate cancer incidence and aggressiveness</span>''' | ||
*#* | *##'''<span style="color:#ff0000">Family history</span>''' | ||
*#** | *##* '''≈15% of prostate cancer patients have the familial or hereditary form''' | ||
*#*** | *##* Risk varies according to the number of affected family numbers, their degree of relatedness, and the age at which they were affected | ||
*##** Father affected: relative risk (RR) 2.2x | |||
*#* ''' | *##** Brother affected: RR 3.4x | ||
*#* | *##**First-degree family member affected, age <65 at diagnosis: RR 3.3x | ||
*##** >2 first-degree relatives affected: RR 5.1x | |||
*#* | *##** Second-degree relative affected: RR 1.7x | ||
*#* | *##* '''<span style="color:#ff0000">Criteria for "strong" family history (2):</span>''' | ||
*##*#'''<span style="color:#ff0000">≥1 brother or father OR ≥2 male relatives with one of the following (3):</span>''' | |||
*# | *##*##'''<span style="color:#ff0000">Diagnosed with prostate cancer at age <60 years</span>''' | ||
*# | *##*##'''<span style="color:#ff0000">Any of whom died of prostate cancer</span>''' | ||
*#*#''' | *##*##'''<span style="color:#ff0000">Any of whom had metastatic prostate cancer.</span>''' | ||
*##*#'''<span style="color:#ff0000">Family history of other cancers with ≥2 cancers in hereditary breast and ovarian cancer syndrome or Lynch syndrome spectrum.</span>''' | |||
*##*#* '''See associated cancers above''' | |||
*#* | *##* '''<span style="color:#ff0000">Patients with a "strong" family history should ideally be genotyped</span>[https://pubmed.ncbi.nlm.nih.gov/37096582/]''' | ||
*#* | *##** '''Genotype is to ascertain whether there is presence of a pathogenic variant (e.g., BRCA1/2, Lynch Syndrome, ATM, CHEK2) or one or more of a growing set of identified germline DNA damage-repair mutations found in patients with metastatic prostate cancer diagnoses.''' | ||
*# | *##'''<span style="color:#ff0000">Ethnicity</span>''' | ||
*##* '''<span style="color:#ff0000">Incidence in Blacks > Whites</span> > Hispanics > Asian-Americans''' | |||
*##**Estimated incidence in Blacks is 1.7x higher than Whites and 2x higher than Hispanics[https://pubmed.ncbi.nlm.nih.gov/36633525/] | |||
*##* Males of Asian descent living in the US have a lower incidence compared to white Americans, but their risk is higher than that of Asians living in Asia, suggesting a dietary, lifestyle, environmental factor | |||
*#'''<span style="color:#ff0000">Age</span>''' | *#'''<span style="color:#ff0000">Age</span>''' | ||
*#*Prevalence of prostate cancer from autopsy series in males aged[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485977/][https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682465/] | *#*Prevalence of prostate cancer from autopsy series in males aged[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485977/][https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682465/] | ||
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*#** 70-79: 36% of Caucasians and 51% of African-Americans | *#** 70-79: 36% of Caucasians and 51% of African-Americans | ||
*#** >79: 59% | *#** >79: 59% | ||
*# '''<span style="color:#ff0000">Inflammation</span>''' | *# '''<span style="color:#ff0000">External (1):</span>''' | ||
*#* Likely contributes to development and progression of early-stage disease | *##'''<span style="color:#ff0000">Inflammation</span>''' | ||
*#* Potential triggers for inflammation include dietary carcinogens (especially from cooked meats), '''estrogens''', and infectious agents | *##* Likely contributes to development and progression of early-stage disease | ||
*#* Studies assessing the association between infection and prostate cancer have shown mixed results; some data suggest that history of STIs and prostatitis is associated with increased risk of prostate cancer | *##* Potential triggers for inflammation include dietary carcinogens (especially from cooked meats), '''estrogens''', and infectious agents | ||
*##* Studies assessing the association between infection and prostate cancer have shown mixed results; some data suggest that history of STIs and prostatitis is associated with increased risk of prostate cancer | |||
** '''Polymorphisms''' in both synthetic and metabolic genes, including the '''androgen receptor (AR), the 5-alpha reductase type 2 isoenzyme''', and genes involved in testosterone biosynthesis, have been reported to affect risk | ** '''Polymorphisms''' in both synthetic and metabolic genes, including the '''androgen receptor (AR), the 5-alpha reductase type 2 isoenzyme''', and genes involved in testosterone biosynthesis, have been reported to affect risk | ||
** '''Insulin-like growth factor''' axis is important in prostate cancer risk and progression | ** '''Insulin-like growth factor''' axis is important in prostate cancer risk and progression | ||