Epidemiological data show that reproductive and hormonal factors are involved in the etiology of endometrial cancer, but there is little data on the association with endogenous sex hormone levels. We ...analyzed the association between prediagnostic serum concentrations of sex steroids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition using a nested case–control design of 247 incident endometrial cancer cases and 481 controls, matched on center, menopausal status, age, variables relating to blood collection, and, for premenopausal women, phase of menstrual cycle. Using conditional regression analysis, endometrial cancer risk among postmenopausal women was positively associated with increasing levels of total testosterone, free testosterone, estrone, total estradiol, and free estradiol. The odds ratios (ORs) for the highest versus lowest tertile were 2.66 (95% confidence interval (CI) 1.50–4.72; P=0.002 for a continuous linear trend) for estrone, 2.07 (95% CI 1.20–3.60; P=0.001) for estradiol, and 1.66 (95% CI 0.98–2.82; P=0.001) for free estradiol. For total and free testosterone, ORs for the highest versus lowest tertile were 1.44 (95% CI 0.88–2.36; P=0.05) and 2.05 (95% CI 1.23–3.42; P=0.005) respectively. Androstenedione and dehydroepiandrosterone sulfate were not associated with risk. Sex hormone-binding globulin was significantly inversely associated with risk (OR for the highest versus lowest tertile was 0.57, 95% CI 0.34–0.95; P=0.004). In premenopausal women, serum sex hormone concentrations were not clearly associated with endometrial cancer risk, but numbers were too small to draw firm conclusions. In conclusion, relatively high blood concentrations of estrogens and free testosterone are associated with an increased endometrial cancer risk in postmenopausal women.
Evidence is accumulating that elevated circulating insulin-like growth factor I (IGF-I) is related to increased cancer risk. The identification of hormonal, reproductive and lifestyle characteristics ...influencing its synthesis and bioavailability is of particular interest. Data from 400 women, who served as controls in two case–control studies nested within the same prospective cohort study, were combined. IGF-I, IGF-binding proteins 1, 2 and 3 (IGFBP-1, -2, -3) and insulin were measured in serum samples from all subjects and cotinine in 186 samples. Age appears to be the most important determinant of total IGF-I levels in women. Anthropomtric measures, such as body mass index (BMI) or waist-to-hip ratio (WHR) do not seem to influence total IGF-I concentrations in peripheral blood, but may modulate IGF-I bioavailability through insulin-dependent changes in IGFBP-1 and -2 concentrations. Age at menarche, phase of the menstrual cycle at blood draw, parity, menopause, past oral contraceptive or hormone replacement therapy use, and tobacco smoking do not appear to exert an independent effect on IGF-I and its binding proteins. There was some suggestion that regular physical activity may increase total IGF-I and that women with positive family history of breast cancer might have higher IGF-I levels than those without such diagnosis in their relatives.
Associations of breast cancer overall with indicators of exposures during puberty are reasonably well characterized; however, uncertainty remains regarding the associations of height, leg length, ...sitting height and menarcheal age with hormone receptor‐defined malignancies. Within the European Prospective Investigation into Cancer and Nutrition cohort, Cox proportional hazards models were used to describe the relationships of adult height, leg length and sitting height and age at menarche with risk of estrogen and progesterone receptor negative (ER‐PR‐) (n = 990) and ER+PR+ (n = 3,524) breast tumors. Height as a single risk factor was compared to a model combining leg length and sitting height. The possible interactions of height, leg length and sitting height with menarche were also analyzed. Risk of both ER‐PR‐ and ER+PR+ malignancies was positively associated with standing height, leg length and sitting height and inversely associated with increasing age at menarche. For ER+PR+ disease, sitting height (hazard ratios: 1.1495% confidence interval: 1.08–1.20) had a stronger risk association than leg length (1.051.00–1.11). In comparison, for ER‐PR‐ disease, no distinct differences were observed between leg length and sitting height. Women who were tall and had an early menarche (≤13 years) showed an almost twofold increase in risk of ER+PR+ tumors but no such increase in risk was observed for ER‐PR‐ disease. Indicators of exposures during rapid growth periods were associated with risks of both HR‐defined breast cancers. Exposures during childhood promoting faster development may establish risk associations for both HR‐positive and −negative malignancies. The stronger associations of the components of height with ER+PR+ tumors among older women suggest possible hormonal links that could be specific for postmenopausal women.
What's new?
Adult height and early age at menarche are established risk factors for breast cancer. In this study, the authors examined these factors in relation to the hormone‐receptor status of breast tumors, with height divided into leg length vs. sitting height. They found that women who were tall and had an early menarche (≤13 years) had almost double the risk of developing estrogen/progesterone‐positive (ER+PR+) tumors. Leg length and early menarche were also associated with increased risk for receptor‐negative (ER‐PR‐) tumors. In addition, the data suggest possible hormonal links that could be specific for postmenopausal women.
We prospectively evaluated fat intake as predictor of developing breast cancer (BC) subtypes defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 ...receptor (HER2), in a large (n = 337327) heterogeneous cohort of women, with 10062 BC case patients after 11.5 years, estimating BC hazard ratios (HRs) by Cox proportional hazard modeling. High total and saturated fat were associated with greater risk of ER(+)PR(+) disease (HR = 1.20, 95% confidence interval CI = 1.00 to 1.45; HR = 1.28, 95% CI = 1.09 to 1.52; highest vs lowest quintiles) but not ER(-)PR(-) disease. High saturated fat was statistically significantly associated with greater risk of HER2(-) disease. High saturated fat intake particularly increases risk of receptor-positive disease, suggesting saturated fat involvement in the etiology of this BC subtype.
OBJECTIVE:To examine the associations of maternal and child characteristics with early pregnancy maternal concentrations of testosterone, androstenedione, progesterone, 17-hydroxyprogesterone, and ...estradiol (E2).
METHODS:We analyzed these hormones among 1,343 women with singleton pregnancies who donated serum samples to the Finnish Maternity Cohort from 1986 to 2006 during the first half of pregnancy (median 11 weeks). The associations of maternal and child characteristics with hormone concentrations were investigated by correlation and multivariable regression.
RESULTS:Women older than age 30 years had lower androgen and E2 but higher progesterone concentrations than women younger than that age. Multiparous women had 14% lower testosterone, 11% lower androstenedione and 17-hydroxyprogesterone, 9% lower progesterone, and 16% lower E2 concentrations compared with nulliparous women (all P<.05). Smoking mothers had 11%, 18%, and 8% higher testosterone, androstenedione, and 17-hydroxyprogesterone levels, respectively, but 10% lower progesterone compared with nonsmoking women (all P<.05). E2 concentrations were 9% higher (P<.05) among women with a female fetus compared with those with a male fetus.
CONCLUSION:Parity, smoking, and, to a lesser extent, maternal age and child sex are associated with sex steroid levels during the first half of a singleton pregnancy. The effects of smoking on the maternal hormonal environment and the possible long-term deleterious consequences on the fetus deserve further evaluation.
LEVEL OF EVIDENCE:II
Knowledge of the stability of serum samples stored in large biobanks is pivotal for reliable assessment of hormone-dependent disease risks. We studied the effects of sample storage time and season of ...serum sampling on the stability of 25-hydroxy vitamin D (25-OHD) and androstenedione in a stratified random sample of 402 women, using paired sera from the Finnish Maternity Cohort. Serum samples selected were donated between 6 and 24 yr ago. The storage time did not affect serum 25-OHD and androstenedione levels. However, there was a significant mean difference in the 25-OHD levels of sera withdrawn during winter (first sample) vs. during summer (second sample; -18.4 nmol/l, P <or= 0.001). Also at the individual level, there were significant differences in average 25-OHD levels between individuals with the paired sera taken at winter-winter compared with other alternatives (summer-winter, winter-summer, and summer-summer). The androstenedione levels showed no such differences. Long-term storage does not affect serum 25-OHD and androstenedione levels, but sampling season is an important determinant of 25-OHD levels. Stored serum samples can be used to study disease associations with both hormones. However, sampling season needs to be taken into account for 25-OHD by considering matching and stratification and, if possible, serial sampling.
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Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Results from case‐control and prospective studies suggest a moderate positive association between obesity and height and differentiated thyroid carcinoma (TC). Little is known on the relationship ...between other measures of adiposity and differentiated TC risk. Here, we present the results of a study on body size and risk of differentiated TC based on a large European prospective study (EPIC). During follow‐up, 508 incident cases of differentiated TC were identified in women, and 58 in men. 78% of cases were papillary TC. Cox proportional hazard models were used to estimate hazard ratios (HRs). In women, differentiated TC risk was significantly associated with body mass index (BMI, kg/m2) (HR highest vs lowest quintile = 1.41, 95% CI: 1.03–1.94); height (HR = 1.61; 95% CI: 1.18–2.20); HR highest vs lowest tertile waist (HR = 1.34, 95% CI: 1.00–1.79) and waist‐to‐hip ratio (HR = 1.42, 95% CI: 1.05–1.91). The association with BMI was somewhat stronger in women below age 50. Corresponding associations for papillary TC were similar to those for all differentiated TC. In men the only body size factors significantly associated with differentiated TC were height (non linear), and leg length (HR highest vs. lowest tertile = 3.03, 95% CI: 1.30–7.07). Our study lends further support to the presence of a moderate positive association between differentiated TC risk and overweight and obesity in women. The risk increase among taller individuals of both sexes suggests that some genetic characteristics or early environmental exposures may also be implicated in the etiology of differentiated TC.
Results from prospective studies on premenopausal serum hormone levels in relation to breast cancer risk have been inconclusive, especially with regard to tumor subtypes. Using a case–control study ...nested within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (801 breast cancer cases and 1,132 matched control subjects), we analyzed the relationships of prediagnostic serum estradiol, free estradiol, progesterone, testosterone, free testosterone and sex hormone‐binding globulin (SHBG) levels with the risk of breast cancer by estrogen and progesterone receptor‐positive and ‐negative breast tumors and by age at diagnoses. Higher prediagnostic serum levels of testosterone and free testosterone were associated with an increased overall risk of breast cancer ORQ4‐Q1 = 1.56 (95% CI 1.15–2.13), ptrend = 0.02 for testosterone and ORQ4‐Q1 = 1.33 (95% CI 0.99–1.79), ptrend = 0.04 for free testosterone, but no significant risk association was observed for estradiol, free estradiol, progesterone and SHBG. Tests for heterogeneity between receptor‐positive and ‐negative tumors were not significant. When analysis were stratified by age at tumor diagnosis, the odds ratios observed for estradiol were stronger and borderline significant for breast cancer diagnosed at age less than 50 ORQ4‐Q1 = 1.32 (95% CI 0.87–2.01), ptrend = 0.05 compared to breast cancer diagnosed at age 50 or above ORQ4‐Q1 = 0.94 (95% CI 0.60–1.47), ptrend = 0.34, phet = 0.04. In conclusion, our data indicate that higher premenopausal circulating testosterone levels are associated with an increased risk of developing breast cancer, but do not show a significant association of estradiol or progesterone with breast cancer risk, overall, by menstrual cycle phase or by tumor receptor status, although a possible risk increase with higher estradiol levels for tumors diagnosed before age 50 was seen.
What's new?
Sex hormones have often been connected with the development of breast cancer, and estrogens have clear pro‐proliferative effects on breast cancer cells. In this large prospective study, the authors underscore a direct association of premenopausal levels of testosterone with subsequent breast cancer risk. By contrast, no direct relationship between premenopausal estrogen and progesterone levels with increased breast cancer risk was observed although a weak association between higher estradiol levels and increased risk for tumors diagnosed before age 50 was noted. The authors point to the possibility that a conversion from androgen to estrogen might take place in the breast that may mechanistically explain the increased risk in breast cancer development when androgens are high.
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