Phytoestrogen exposure, polymorphisms in COMT, CYP19, ESR1, and SHBG genes, and their associations with prostate cancer risk.
Prospective phytoestrogen exposure was assessed using both biomarkers and estimates of intake in 89 British men recruited into the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition study, men who subsequently developed prostate cancer. Results were compared with those from 178 healthy men matched by age and date of recruitment. Levels of seven phytoestrogens (daidzein, genistein, glycitein, O-desmethylangolensin, equol, enterodiol, and enterolactone) were measured in spot urine and serum samples. Five single-nucleotide polymorphisms in COMT, CYP19, ESR1, and SHBG genes were genotyped. Urinary levels of all phytoestrogens correlated strongly with serum levels. Correlation coefficients ranged from 0.63 (glycitein) to 0.88 (daidzein) (P < 0.001). Urinary and serum levels correlated significantly with isoflavone intake assessed from food diaries (R = 0.15-0.20; P < 0.05) but not with that from a food-frequency questionnaire. Odds ratios for phytoestrogen exposure, as assessed using the four methods, were not significantly associated with prostate cancer risk (P = 0.15-0.94). Men with the CC genotype for the ESRI PvuII polymorphism had significantly higher risk for prostate cancer compared with men with the TT genotype [adjusted odds ratio = 4.65 (1.60-13.49); P = 0.005]. Our results utilizing a combined prospective exposure provide no evidence that phytoestrogens alter prostate cancer risk in British men, whereas the C allele for the PvuII polymorphism may be associated with increased risk.
Low
Yen-Ling
YL
MRC Dunn Human Nutrition Unit, Cambridge CB2 2XY, UK.
Taylor
James I
JI
Grace
Philip B
PB
Mulligan
Angela A
AA
Welch
Ailsa A
AA
Scollen
Serena
S
Dunning
Alison M
AM
Luben
Robert N
RN
Khaw
Kay-Tee
KT
Day
Nick E
NE
Wareham
Nick J
NJ
Bingham
Sheila A
SA
D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000652:urine; D004032:Diet; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D048789:Phytoestrogens / Q000008:administration & dosage / Q000097:blood / Q000652:urine; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
D015415:Biomarkers; D048789:Phytoestrogens