Risk Flashcards
What is PSA?
serine protease 34KD glycoprotein
pre pro PSA to pro PSA
free PSA, bound to ACT, bound to AMG
activated by AR
BRCA study Embrace Eur Urol
Impact study eur urol 2019
2-5 x higher risk of developing prostate cancer and more aggressive BRCA 2 than general population
Impact
More higher risk PC in BRCA 2 carriers vs mom carriers
Lifetime risk diagnosis ethnicity
white
black
asian
1/8 to 1/9 white
1/4 black men - afra caribbean relative incidence 1.6 compared to white men
1/13 Asian
Lifetime risk dying ethnicity
1/24 white man
1/12 black
post morten studies prostate cancer
50 year olds
80 year olds
30% 50 year olds
70% of 80 year olds
median age diagnosis
66 yo
% prostate cancer occuring in over 75
% diagnosed in over 65
71%
75%
% hereditary prostate cancer
9%
definition hereditary prostate cancer
3+ affected relative or 2+ with early onset disease less than 55 yo
gene mutations associated
single defect chronosome 1q
8p
13q-BRCA 2
relative risk with 1st degree relative
one 1st degree
two 1st degree
hereditary
2x
4x
5x
relative risk with 1st degree relative
one 1st degree
two 1st degree
hereditary
2x
4x
5x
REDUCE study
lower risk of low grade PCA with obesity, higher risk of high grade PCA
lower circulating androgens - causing lower PSA
higher free IGF-1 levels
no association LDL HDL cholesterol levels
statins do not protect against PCa
prostate cancer and obesity
lower risk of low grade PCA with obesity, higher risk of high grade PCA
lower circulating androgens - causing lower PSA
higher free IGF-1 levels
no association LDL HDL cholesterol levels
statins do not protect against PCa
relationship vitamin D with prostate cancer
u shaped relationship
polymorphisms of vit d recetpros
testosterone risk with PCa
no extra risk when given to hypogonadal men
5ARi and prostate cancer evidence
PCPT trial Thompson NEJM
proposed lower incidence of Pca but higher risk of high grade PCA
gene fusions in PCA
most commonly involves fusion of TMPRSS2 to members of ETS family
promotes genes under androgenic control
other genes implicated in PCa 4
cell cycle genes
DNA repair genes
tumour suppressor genes
hormonal response genes
REDUCE
2010
reduction of dutasteride of prostate cancer events
RRR 22% of prostate cancer
higher incidence of high grade prostate cancer
PCPT trial
thompson NEJM 2003
finasteride vs placebo 7 years
25% RRR incidence prostate cancer 24% vs 18%
higher incidence high grade prostate cancer 6.4% vs 5.1%
SELECT trial vitamin E
Klein 2011
vitamin E increased incidence prostate cancer
combination treatment had no effect
