Sex steroid hormones and the androgen receptor gene CAG repeat and subsequent risk of prostate cancer in the prostate-specific antigen era.
OBJECTIVE
Sex steroid hormones are thought to contribute to the growth, differentiation, and progression of prostate cancer. We investigated plasma levels of sex steroid hormones and length of the androgen receptor gene CAG repeat in relation to incident prostate cancer diagnosed in the prostate-specific antigen (PSA) era.


METHODS
Using a nested case-control design, we included 460 prostate cancer cases diagnosed after providing a blood specimen in 1993 but before February 1998 among men in the Health Professionals Follow-up Study. Controls were 460 age-matched men without prostate cancer who had a screening PSA test after the date of providing a blood specimen. We measured plasma concentrations of total testosterone, free testosterone, dihydrotestosterone, androstanediol glucuronide, estradiol, and sex hormone binding globulin (SHBG) and determined the length of the androgen receptor gene CAG repeat. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of prostate cancer.


RESULTS
Mean concentrations of the sex steroids adjusted for SHBG, and mean CAG repeat length did not differ significantly between the prostate cancer cases and controls. No significant associations with total prostate cancer were detected for plasma total testosterone concentration (comparing highest versus lowest quartiles: OR, 0.78; 95% CI, 0.48-1.28; P(trend) = 0.73) or the other sex hormones after adjusting for SHBG. However, plasma total testosterone concentration was positively associated with low-grade disease (Gleason sum < 7: OR, 1.91; 95% CI, 0.89-4.07; P(trend) = 0.02) and inversely associated with high-grade disease (Gleason sum > or = 7: OR, 0.26; 95% CI, 0.10-0.66; P(trend) = 0.01). Similar patterns for grade were observed for free testosterone. Short CAG repeat length was not associated with total prostate cancer (< or = 19 versus > or = 24: OR, 0.84; 95% CI, 0.57-1.23; P(trend) = 0.22) or grade of disease. No clear associations with regionally invasive or metastatic (> or = T3b, N1, or M1) were found for any of the hormones or the CAG repeat, although the number of these cases was small.


CONCLUSIONS
The overall lack of association of prostate cancer diagnosed in the PSA era with sex steroid hormones and the androgen receptor gene CAG repeat length is consistent with the hypothesis that these factors do not substantially contribute to the development of early prostate cancer in the PSA era. The influence of plasma total and free testosterone concentrations on prostate cancer grade merits further evaluation.
Platz
Elizabeth A
EA
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Room E6138, 615 North Wolfe Street, Baltimore, MD 21205, USA. eplatz@jhsph.edu
Leitzmann
Michael F
MF
Rifai
Nader
N
Kantoff
Philip W
PW
Chen
Yen-Ching
YC
Stampfer
Meir J
MJ
Willett
Walter C
WC
Giovannucci
Edward
E
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000032:analysis*; D011795:Surveys and Questionnaires; D014481:United States / Q000453:epidemiology
D012739:Gonadal Steroid Hormones; D011944:Receptors, Androgen; D011956:Receptors, Cell Surface; D012738:Sex Hormone-Binding Globulin; C063572:sex hormone-binding globulin receptor; D017430:Prostate-Specific Antigen