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Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women.
Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
Vise andre og tillknytning
2004 (engelsk)Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 108, nr 3, s. 425-432Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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.

sted, utgiver, år, opplag, sider
2004. Vol. 108, nr 3, s. 425-432
Emneord [en]
Estradiol, estrone, testosterone, androstenedione, DHEAS, SHBG, endometrial cancer, cohort study
HSV kategori
Identifikatorer
URN: urn:nbn:se:umu:diva-15447DOI: 10.1002/ijc.11529PubMedID: 14648710Scopus ID: 2-s2.0-10744223927OAI: oai:DiVA.org:umu-15447DiVA, id: diva2:155119
Tilgjengelig fra: 2007-11-23 Laget: 2007-11-23 Sist oppdatert: 2023-03-23bibliografisk kontrollert
Inngår i avhandling
1. Endogenous hormones in the etiology of ovarian and endometrial cancers
Åpne denne publikasjonen i ny fane eller vindu >>Endogenous hormones in the etiology of ovarian and endometrial cancers
2004 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

The main purpose of this thesis was to examine the relationship of pre-diagnostic circulating levels of sex-steroids (androgens and estrogens), sex hormone binding globuline (SHBG), insulin-like growth factor-I (IGF-I), IGF binding proteins (BP) and C-peptide (as a marker of pancreatic insulin secretion) with risk of ovarian and endometrial cancer. Additionally, the interrelationships of body mass index (BMI), sex-steroids, IGF-I and IGFBP-3 were examined. Two case-control studies were nested within 3 prospective cohort studies centered in New York (USA), Umeå (Sweden) and Milan (Italy). The ovarian study included 132 cancer cases. The endometrial study included 166 cancer cases in the IGF-I and C-peptide component and 124 postmenopausal cases in the sex-steroids component. For each case, two controls matching the case for cohort, age, menopausal status and date at recruitment were selected. In total 286 and 315 controls were included in the ovarian and endometrial cancer studies, respectively. Odds ratios (OR) and their 95% confidence intervals (CI) for cancer risk associated with increasing hormone concentrations were estimated by conditional logistic regression. The cross-sectional analysis was based on anthropometric and hormonal data from 620 controls selected for the two nested case-control studies. There was no association of prediagnostic androstenedione, testosterone, DHEAS, SHBG or estrone with ovarian cancer risk in the whole study population or in women who were pre- or postmenopausal at blood donation. In the premenopausal group, risk appeared to increase with increasing androstenedione (OR (95% CI) for the highest tertile: 2.35 (0.81-6.82), p=0.12). There was no association of IGF-I, IGFBP-1, 2, 3 or C-peptide concentrations with risk of ovarian cancer risk in the study group as a whole. In analyses restricted to subjects who had developed ovarian cancer at an early age (<55), circulating IGF-I was directly and strongly associated with risk (OR (95% CI): 4.74 (1.20-18.7), p<0.05 for the highest IGF-I tertile). In the endometrial study, previous observations were confimed that elevated circulating estrogens and androgens and decreased SHBG increase risk of developing endometrial malignancy after menopause. Multivariate ORs (95% CI) for endometrial cancer for quartiles with the highest hormone levels were: 4.13 (1.76-9.72), p<0.001 for estradiol; 3.67 (1.71-7.88), p=0.001 for estrone; 2.15 (1.05-4.40), p<0.04 for androstenedione; 1.74 (0.88-3.46), p=0.06 for testosterone; 2.90 (1.42-5.90), p<0.01 for DHEAS and 0.46 (0.20-1.05), p<0.01 for SHBG. Prediagnostic IGF-I, IGFBP-1, -2 and –3 were not related to risk of endometrial cancer in the whole study population. In postmenopausal women, levels of IGFBP-1 were inversely related to risk with an OR for the highest quartile of 0.36 (0.13-0.95), p<0.05. Endometrial cancer risk increased with increasing levels of C-peptide (p<0.01), up to an OR of 4.40 (1.65-11.7) for the highest quintile after adjustment for BMI and other confounders. The cross-sectional analyses showed that in both pre- and postmenopausal women SHBG decreased with increasing BMI. In the postmenopausal group, estrogens, testosterone and androstenedione increased with BMI, while the association with IGF-I was non-linear, the highest mean IGF-I concentration being observed in women with BMI between 24 and 25. In postmenopausal women, IGF-I was positively related to androgens, inversely correlated with SHBG, and was not correlated with estrogens. In conclusion, elevated pre-diagnostic sex-steroids, IGF-I or C-peptide increase risk of developing ovarian and endometrial cancer. BMI influences the circulating levels of these hormones, especially after menopause.

Publisher
s. 100
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 878
Emneord
Public health, ovarian cancer, endometrial cancer, sex-steroid hormones, sex-hormone binding globulin, insulin-like growth factor-I, insulin-like growth factor bidning proteins, C-peptide, Folkhälsomedicin
HSV kategori
Forskningsprogram
epidemiologi
Identifikatorer
urn:nbn:se:umu:diva-215 (URN)91-7305-612-X (ISBN)
Disputas
2004-04-16, Hörsal E04, By 6E, Norrlands universitetssjukhus, Umeå, 09:00
Opponent
Veileder
Tilgjengelig fra: 2004-03-23 Laget: 2004-03-23 Sist oppdatert: 2010-08-06bibliografisk kontrollert

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