Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women.
Experimental and epidemiological data support a role for sex steroid hormones in the pathogenesis of endometrial cancer. The associations of pre-diagnostic blood concentrations of estradiol, estrone, testosterone, androstenedione, DHEAS and SHBG with endometrial cancer risk were investigated. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). Cases were 124 postmenopausal women with invasive endometrial cancer. For each case, 2 controls were selected, matching the case on cohort, age and date of recruitment. Only postmenopausal women who did not use exogenous hormones at the time of blood donation were included. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated by conditional logistic regression. ORs (95% CI) for endometrial cancer for quartiles with the highest hormone levels, relative to the lowest were as follows: 4.13 (1.76-9.72), p(trend) = 0.0008 for estradiol, 3.67 (1.71-7.88), p(trend) = 0.0007 for estrone, 2.15 (1.05-4.40), p(trend) = 0.04 for androstenedione, 1.74 (0.88-3.46), p(trend) = 0.06 for testosterone, 2.90 (1.42-5.90), p(trend) = 0.002 for DHEAS and 0.46 (0.20-1.05), p(trend) = 0.01 for SHBG after adjustment for body mass index, use of oral contraceptives and hormone replacement therapy. The results of our multicenter prospective study showed a strong direct association of circulating estrogens, androgens and an inverse association of SHBG levels with endometrial cancer in postmenopausal women. The effect of elevated androstenedione and testosterone levels on disease risk seems to be mediated mainly through their conversion to estrogens, although an independent effect of androgens on tumor growth cannot be ruled out, in particular in the years close to diagnosis.
Lukanova
Annekatrin
A
International Agency for Research on Cancer, Lyon, France.
Lundin
Eva
E
Micheli
Andrea
A
Arslan
Alan
A
Ferrari
Pietro
P
Rinaldi
Sabina
S
Krogh
Vittorio
V
Lenner
Per
P
Shore
Roy E
RE
Biessy
Carine
C
Muti
Paola
P
Riboli
Elio
E
Koenig
Karen L
KL
Levitz
Mortimer
M
Stattin
Pär
P
Berrino
Franco
F
Hallmans
Göran
G
Kaaks
Rudolf
R
Toniolo
Paolo
P
Zeleniuch-Jacquotte
Anne
A
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D004198:Disease Susceptibility; D016889:Endometrial Neoplasms / Q000097:blood* / Q000453:epidemiology*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood*; D020249:Hormone Replacement Therapy; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009518:New York / Q000453:epidemiology; D017698:Postmenopause; D011446:Prospective Studies; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology
D012739:Gonadal Steroid Hormones