The rs743572 common variant in the promoter of CYP17A1 is not associated with prostate cancer risk or circulating hormonal levels.
OBJECTIVE
To use a large population-based case-control study to test the association between the common genetic variant rs743572 (-34 T to C), prostate cancer risk and circulating levels of several hormones.


METHODS
A previous meta-analysis concluded that reported associations between rs743572 in the promoter of CYP17A1 and prostate cancer risk might reflect publication bias, but a few recent studies reported associations with prostate cancer risk and data suggesting that rs743572 is functional. We genotyped 824 prostate cancer cases and 737 population-based controls, and applied unconditional logistic regression to estimate the association between rs743572 and prostate cancer risk. We also used linear regression of transformed testosterone, androstanediol glucuronide, dehydroepiandrosterone sulphate, androstenedione, sex hormone-binding globulin and oestradiol (circulating levels) measured for controls, to estimate the association between these levels and rs743572. The linear models were adjusted for age and laboratory batch.


RESULTS
Men with different genotypes had similar circulating levels of all the hormones measured (all P < 0.05). In the case-control comparison using unconditional unadjusted logistic regression, the odds ratios (95% confidence interval) for prostate cancer were 1.07 (0.87-1.32) and 0.94 (0.71-1.25) for the dominant and recessive models, respectively, and for the co-dominant model, 1.10 (0.88-1.36) and 0.99 (0.73-1.35) for carriers of one or two copies of the C allele, respectively. There was no evidence of heterogeneity in the odds ratios by tumour stage (all P > 0.3) and grade (all P > 0.3).


CONCLUSIONS
The results of the present study are consistent with the conclusions of the previous meta-analysis, and suggest that rs743572 has no role in the risk of prostate cancer for men of Caucasian origin.
Severi
Gianluca
G
Cancer Epidemiology Centre, The Cancer Council Victoria, Carlton, Victoria 3053, Australia. gianluca.severi@cancervic.org.au
Hayes
Vanessa M
VM
Tesoriero
Andrea A
AA
Southey
Melissa C
MC
Hoang
Hoa N
HN
Padilla
Emma J D
EJ
Morris
Howard A
HA
English
Dallas R
DR
Sutherland
Robert L
RL
Boyle
Peter
P
Hopper
John L
JL
Giles
Graham G
GG
D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics*; D012307:Risk Factors; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*
D006728:Hormones; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase