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- Lukanova, Annekatrin, et al.
(author)
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Circulating levels of insulin-like growth factor-I and risk of ovarian cancer.
- 2002
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 101:6, s. 549-554
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Journal article (peer-reviewed)abstract
- Insulin-like growth factor (IGF)-I, a mitogenic and anti-apoptotic peptide, has been implicated in the development of several cancers. We hypothesized that high circulating IGF-I concentrations may be associated with an increased risk of ovarian cancer. A case-control study was nested within 3 prospective cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). One hundred thirty-two women with primary invasive epithelial ovarian cancer diagnosed at least 1 year after blood donation were case subjects. For each case, 2 control subjects were selected, matching the case subject on cohort, menopausal status, age and date of recruitment (n = 263). Only women who did not use exogenous hormones at blood donation were included in the study. There was no association between IGF-I concentrations and ovarian cancer risk in the study group as a whole. In analyses restricted to subjects who had developed ovarian cancer at a young age (<55), circulating IGF-I was directly and strongly associated with ovarian cancer risk (OR = 4.97; 95% CI = 1.22-20.2 for the top vs. the bottom IGF-I tertile after adjustment for parity, BMI categories and smoking). There was no significant association of IGF binding protein-3 with ovarian cancer risk. We found a strong direct relationship between circulating IGF-I levels and risk of developing ovarian cancer before age 55. Additional, larger studies of this association are needed to provide more precise estimates of effect.
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- Lukanova, Annekatrin, et al.
(author)
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Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women.
- 2004
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 108:3, s. 425-432
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Journal article (peer-reviewed)abstract
- 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.
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- Lukanova, Annekatrin, et al.
(author)
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Circulating levels of sex steroid hormones and risk of ovarian cancer.
- 2003
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 104:5, s. 636-642
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Journal article (peer-reviewed)abstract
- Experimental and epidemiological evidence supports a role for sex steroid hormones in the pathogenesis of ovarian cancer. We investigated the association between ovarian cancer risk and pre-diagnostic blood concentrations of testosterone, androstenedione, DHEAS, estrone and SHBG. A case-control study nested within 3 cohorts, in New York (USA), Umeå (Sweden) and Milan (Italy), included 132 subjects with primary invasive epithelial ovarian cancer. For each case subject, 2 controls were selected who matched a case on cohort, menopausal status, age and date of recruitment and, if premenopausal, day of the menstrual cycle at blood donation. Only women who did not use exogenous hormones at blood donation were included in the study. Conditional logistic regression was used to relate cancer risk to sex steroid hormone concentrations with adjustment for potential confounders. No clear association was observed between ovarian cancer risk and any of the 5 hormones under study. In the premenopausal group, the risk appeared to increase with increasing blood concentrations of androstenedione (upper vs. lower tertile OR = 2.35; 95% CI = 0.81-6.82.), but the small number of subjects in the sub-group precluded reaching unambiguous conclusions about such association. Our study does not support previous observations relating elevations in blood levels of the major sex steroid hormones to an increased risk of ovarian cancer, but offers some evidence that elevated circulating androstenedione before menopause may be associated with increased ovarian cancer risk.
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- Lukanova, Annekatrin, et al.
(author)
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Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer.
- 2004
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 108:2, s. 262-268
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Journal article (peer-reviewed)abstract
- Conditions related to chronic hyperinsulinemia, such as obesity, noninsulin dependent diabetes mellitus and polycystic ovary syndrome, are associated with an increased risk of endometrial cancer. Elevated plasma IGF-I and decreased levels of IGF-binding proteins have been shown to be associated with increased risk of several cancer types that are frequent in affluent societies. We investigated for the first time in a prospective study the association of pre-diagnostic blood concentrations of C-peptide (a marker of pancreatic insulin production), IGF-I, IGFBP-1, -2 and -3 with endometrial cancer risk. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). It included 166 women with primary invasive endometrial cancer and 315 matched controls, of which 44 case and 78 control subjects were premenopausal at recruitment. Endometrial cancer risk increased with increasing levels of C-peptide (ptrend = 0.0002), up to an odds ratio (OR) of 4.76 [95% confidence interval (CI) = 1.91-11.8] for the highest quintile. This association remained after adjustment for BMI and other confounders [OR for the top quintile = 4.40 (1.65-11.7)]. IGFBP-1 levels were inversely related to endometrial cancer [ptrend = 0.002; OR in the upper quintile = 0.30 (0.15-0.62)], but the association was weakened and lost statistical significance after adjustment for confounders [ptrend = 0.06; OR in the upper quintile = 0.49 (0.22-1.07)]. Risk was unrelated to levels of IGF-I, IGFBP-2 and IGFBP-3. Chronic hyperinsulinemia, as reflected by increased circulating C-peptide, is associated with increased endometrial cancer risk. Decrease in the prevalence of chronic hyperinsulinemia, through changes in lifestyle or medication, is expected to prevent endometrial cancer.
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- Lukanova, Annekatrin, et al.
(author)
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Risk of ovarian cancer in relation to prediagnostic levels of C-peptide, insulin-like growth factor binding proteins-1 and -2 (USA, Sweden, Italy).
- 2003
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In: Cancer Causes and Control. - 0957-5243 .- 1573-7225. ; 14:3, s. 285-292
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate the association of prediagnostic circulating levels of C-peptide, as a marker of pancreatic insulin secretion, and IGF binding proteins -1 and -2, as indicators of the biologically active IGF-I concentration, with risk of developing ovarian cancer. METHODS: The study was nested within three prospective cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). Case subjects were 132 women with primary invasive epithelial ovarian cancer diagnosed at least one year after blood donation. For each case, two control subjects were selected, matching the case subject on cohort, menopausal status, age and date of recruitment (n = 263). Only women who did not use exogenous hormones at blood donation were included in the study. RESULTS: Odds ratios and their 95% confidence intervals for risk of developing ovarian cancer over quartiles of peptides concentrations after adjustment for BMI and fasting were: 1.00, 0.66 (0.35-1.23), 0.96 (0.51-1.82) and 0.89 (0.44-1.81) for C-peptide; 1.00, 1.10 (0.58-2.09), 1.07 (0.55-2.04) and 0.79 (0.38-1.62) for IGFBP-1; and 1.00, 1.01 (0.54-1.89), 0.98 (0.51-1.88) and 0.87 (0.45-1.68) for IGFBP-2. In women who had ovarian cancer diagnosis before age 55 the ORs for the top tertiles of IGFBP-1 and IGFBP-2 were 0.51 (0.18-1.49) and 0.53 (0.18-1.54), respectively. CONCLUSIONS: This study does not support an independent direct etiological role of C-peptide in ovarian cancer pathogenesis, but suggests a possible protective effect of circulating IGFBP-1 and -2 in women who develop ovarian cancer before age 55.
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