Prostate Cancer
Risk Factors, Diet & Chemoprevention
Risk Factors
• HEREDITARY: 10% 43% < 55yrs 1st Relative 2 fold increase 2-3 1st relat 5-11 younger increase risk Autosomal dominant
• ANDROGENS:
Contentious
• GENETIC POLYMORPHISMS: 5 a- reductase Type 2: converts to more potent DHT SRD5A2 Longer allele repeats in A men with Cap that not Cytochrome P459 C17a (CYP17) AI is more active allele P4503A4 (CYP3A4) eggressive Cap in white + AA
Androgen Receptor
CAG repeats – length 1/ activity short - CaP
Vit D receptor: inhibits growth + induces differentiation
IGF-1: 3 studies show levels = risk VASECTOMY: Giovannuci 1993 prospect + retrospect risk 1.6 RR Stanford 1999 no risk case control Seattle
DIET
• FAT: mortality rate correlate with fat diet low fat in rats little growth CaP High fat growth CaP Alters Androgen fat testosterone source of free radicals, pro-inflam fatty acid metabolites --- carcinogenic Giovannuci diet fat 1.6 RR advanced CaP Red meat dairy linolenic acid
• CALCIUM: DIET --- risk
Vit D
• Vit D: 2 studies low Vit D north USA CaP ASSOCIATION Ca Ph diet lower Vit D CaP Vit D receptors in cells lower proliferation Mice studies, cells Calcitriol ----- hypercalcaemia
TOMATO
Health Professional Follow-up study CaP risk with tomato -- raw, pizza, baked beans Cooked tomatoes x 16/mth x 15% 36% with tomato sauce not juice Cohen veg but not cooked tomatoes Mop up free radicals anti-oxidant products LYCOPENE Inhibits IGF-1 signalling Cooking alters bioavailability Castration alters metabolism of lycopene 1 per day 5 per week
• SELENIUM: skin cancer study diet suppliment -- CaP 200ug/day Cap 63% Trials for HGPIN, WW, preRRP, -ve bx
• SOY PHYTO-OESTROGENS: ISOFLAVONES Weak oestrogenic effects Genestein Daidzein EGF pathway / angiogenesis Asian diets
• GREEN TEA: polyphenolic anti-oxidants flavenols or catechins EGCG Epidemiol regular drinkers low incidence Inhibit 5 a-reductase AR mRNA PSA from LNCaP cells Inhibits IGF • VITAMIN E: Tocopherols potent anti-oxidants Vit E suppliment Cap 25% risk Low diet + smokers risk death Lung ca study high + smoker Cap 800 iu/day
Chemoprevention
• ANTI-ANDROGENS: NCI 1999 PCPT Proscar Inhibit 5 a-reductase intaprostatic testosterone not DHT
• Retinoic Acid: induce terminal differt in cell lines • Vit D analogues: PSA relapse study calcitriol slower rate of rise of PSA DIET/EXERCISE/SUPPLEMENTS alter androgen/oestrogen ratio
• Red wine --- oestrogenic effect
• Polyunsaturates lower calories lower testosterone • Smoking appears to have no effect