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1.
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2.
  • Allen, Naomi E, et al. (författare)
  • Endogenous sex hormones and endometrial cancer risk in women in the European Prospective Investigation into Cancer and Nutrition (EPIC).
  • 2008
  • Ingår i: Endocrine-Related Cancer. - 1351-0088. ; 15:2, s. 485-497
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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3.
  • Assi, Nada, et al. (författare)
  • A treelet transform analysis to relate nutrient patterns to the risk of hormonal receptor-defined breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)
  • 2016
  • Ingår i: Public Health Nutrition. - 1368-9800. ; 19:2, s. 242-254
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Pattern analysis has emerged as a tool to depict the role of multiple nutrients/foods in relation to health outcomes. The present study aimed at extracting nutrient patterns with respect to breast cancer (BC) aetiology. Design Nutrient patterns were derived with treelet transform (TT) and related to BC risk. TT was applied to twenty-three log-transformed nutrient densities from dietary questionnaires. Hazard ratios (HR) and 95 % confidence intervals computed using Cox proportional hazards models quantified the association between quintiles of nutrient pattern scores and risk of overall BC, and by hormonal receptor and menopausal status. Principal component analysis was applied for comparison. Setting The European Prospective Investigation into Cancer and Nutrition (EPIC). Subjects Women (n 334 850) from the EPIC study. Results The first TT component (TC1) highlighted a pattern rich in nutrients found in animal foods loading on cholesterol, protein, retinol, vitamins B-12 and D, while the second TT component (TC2) reflected a diet rich in -carotene, riboflavin, thiamin, vitamins C and B-6, fibre, Fe, Ca, K, Mg, P and folate. While TC1 was not associated with BC risk, TC2 was inversely associated with BC risk overall (HRQ5 v. Q1=089, 95 % CI 083, 095, P-trend<001) and showed a significantly lower risk in oestrogen receptor-positive (HRQ5 v. Q1=089, 95 % CI 081, 098, P-trend=002) and progesterone receptor-positive tumours (HRQ5 v. Q1=087, 95 % CI 077, 098, P-trend<001). Conclusions TT produces readily interpretable sparse components explaining similar amounts of variation as principal component analysis. Our results suggest that participants with a nutrient pattern high in micronutrients found in vegetables, fruits and cereals had a lower risk of BC.
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4.
  • Campa, Daniele, et al. (författare)
  • The INSIG2 rs7566605 polymorphism is not associated with body mass index and breast cancer risk
  • 2010
  • Ingår i: BMC Cancer. - BioMed Central. - 1471-2407. ; 10, s. 563
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The single nucleotide polymorphism rs7566605, located in the promoter of the INSIG2 gene, has been the subject of a strong scientific effort aimed to elucidate its possible association with body mass index (BMI). The first report showing that rs7566605 could be associated with body fatness was a genome-wide association study (GWAS) which used BMI as the primary phenotype. Many follow-up studies sought to validate the association of rs7566605 with various markers of obesity, with several publications reporting inconsistent findings. BMI is considered to be one of the measures of choice to evaluate body fatness and there is evidence that body fatness is related with an increased risk of breast cancer (BC).METHODS: we tested in a large-scale association study (3,973 women, including 1,269 invasive BC cases and 2,194 controls), nested within the EPIC cohort, the involvement of rs7566605 as predictor of BMI and BC risk.RESULTS AND CONCLUSIONS: In this study we were not able to find any statistically significant association between this SNP and BMI, nor did we find any significant association between the SNP and an increased risk of breast cancer overall and by subgroups of age, or menopausal status.
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5.
  • Cust, Anne E, et al. (författare)
  • Dietary carbohydrates, glycemic index, glycemic load, and endometrial cancer risk within the European Prospective Investigation into Cancer and Nutrition cohort.
  • 2007
  • Ingår i: American Journal of Epidemiology. - 0002-9262. ; 166:8, s. 912-23
  • Tidskriftsartikel (refereegranskat)abstract
    • The associations of dietary total carbohydrates, overall glycemic index, total dietary glycemic load, total sugars, total starch, and total fiber with endometrial cancer risk were analyzed among 288,428 women in the European Prospective Investigation into Cancer and Nutrition cohort (1992-2004), including 710 incident cases diagnosed during a mean 6.4 years of follow-up. Cox proportional hazards models were used to estimate relative risks and 95% confidence intervals. There were no statistically significant associations with endometrial cancer risk for increasing quartile intakes of any of the exposure variables. However, in continuous models calibrated by using 24-hour recall values, the multivariable relative risks were 1.61 (95% confidence interval: 1.06, 2.45) per 100 g/day of total carbohydrates, 1.40 (95% confidence interval: 0.99, 1.99) per 50 units/day of total dietary glycemic load, and 1.36 (95% confidence interval: 1.05, 1.76) per 50 g/day of total sugars. These associations were stronger among women who had never used postmenopausal hormone therapy compared with ever users (total carbohydrates P-heterogeneity = 0.04). Data suggest no association of overall glycemic index, total starch, and total fiber with risk, and a possible modest positive association of total carbohydrates, total dietary glycemic load, and total sugars with risk, particularly among never users of hormone replacement therapy.
6.
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7.
  • Cust, Anne E., et al. (författare)
  • Metabolic syndrome, plasma lipid, lipoprotein and glucose levels, and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)
  • 2007
  • Ingår i: Endocrine-Related Cancer. - Society for Endocrinology. - 1479-6821. ; 14:3, s. 755-767
  • Tidskriftsartikel (refereegranskat)abstract
    • To clarify the role of metabolic factors in endometrial carcinogenesis, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), and examined the relation between prediagnostic plasma lipids, lipoproteins, and glucose, the metabolic syndrome (MetS; a cluster of metabolic factors) and endometrial cancer risk. Among pre- and postmenopausal women, 284 women developed endometrial cancer during follow-up. Using risk set sampling, 546 matched control subjects were selected. From conditional logistic regression models, high-density lipoprotein cholesterol (HDL-C) levels were inversely associated with risk body mass index (BMI)-adjusted relative risk (FR) for top versus bottom quartile 0.61 (95% confidence intervals (CI) 0.38-0.97), P-trend= 0.02). Glucose levels were positively associated with risk (BMI-adjusted RR top versus bottom quartile 1.69 (95% Cl 0.99-2.90), P-trend, = 0.03), which appeared stronger among postmenopausal women (BMI-adjusted RR top versus bottom tertile 2.61 (95% Cl 1.46-4.66), P-trend=0.0006, P-heterogeneity=0.13) and never-users of exogenous hormones (P-heterogeneity=0-005 for oral contraceptive (OC) use and 0.05 for hormone replacement therapy-use). The associations of HDL-C and glucose with risk were no longer statistically significant after further adjustment for obesity-related hormones. Plasma total cholesterol, Low-density lipoprotein cholesterol (LDL-C), and triglycerides were not significantly related to overall risk. The presence of MetS was associated with risk (RR 2.12 (95% CI 1.51-2.97)), which increased with the number of MetS factors (P-trend=0.02). An increasing number of MetS factors other than waist circumference, however, was marginally significantly associated with risk only in women with waist circumference above the median (P-interaction=0-01). None of the associations differed significantly by fasting status. These findings suggest that metabolic abnormalities and obesity may act synergistically to increase endometrial cancer risk.
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9.
  • Dossus, Laure, et al. (författare)
  • Obesity, inflammatory markers, and endometrial cancer risk : a prospective case-control study
  • 2010
  • Ingår i: Endocrine-Related Cancer. - 1351-0088. ; 17:4, s. 1007-1019
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity, a major risk factor for endometrial cancer, is a low-grade inflammatory state characterized by elevated concentrations of cytokines and acute phase reactants. The current study had two aims: first to investigate the associations of C-reactive protein (CRP), interleukin 6 (IL6), and IL1 receptor antagonist (IL1Ra) with endometrial cancer risk and second to examine to which extent these markers can influence the association between obesity and endometrial cancer. We conducted a case-control study, nested within the European Prospective Investigation into Cancer and Nutrition, which comprised 305 incident cases of endometrial cancer and 574 matched controls. CRP, IL6, and IL1Ra were measured in prospectively collected blood specimens by immunoassays. Data were analyzed using conditional logistic regression. All statistical tests were two-sided, and P values <0.05 were considered statistically significant. We observed a significant increase in risk of endometrial cancer with elevated levels of CRP (odds ratio (OR) for top versus bottom quartile: 1.58, 95% confidence interval (CI): 1.03-2.41, P(trend)=0.02), IL6 (OR for top versus bottom quartile: 1.66, 95% CI: 1.08-2.54, P(trend)=0.008), and IL1Ra (OR for top versus bottom quartile: 1.82, 95% CI: 1.22-2.73, P(trend)=0.004). After adjustment for body mass index (BMI), the estimates were strongly reduced and became non-significant. The association between BMI and endometrial cancer was also substantially attenuated (∼10-20%) after adjustment for inflammatory markers, even when the effects of C-peptide or estrone had already been taken into account. We provided epidemiological evidence that chronic inflammation might mediate the association between obesity and endometrial cancer and that endometrial carcinogenesis could be promoted by an inflammatory milieu.
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10.
  • Dossus, Laure, et al. (författare)
  • Reproductive risk factors and endometrial cancer: the European Prospective Investigation into Cancer and Nutrition
  • 2010
  • Ingår i: International Journal of Cancer. - John Wiley & Sons. - 0020-7136. ; 127:2, s. 442-451
  • Tidskriftsartikel (refereegranskat)abstract
    • Endometrial cancer risk has been associated with reproductive factors (age at menarche, age at menopause, parity, age at first and last birth, time since last birth and use of oral contraceptives (OCs)]. However, these factors are closely interrelated and whether they act independently still requires clarification. We conducted a study to examine the association of menstrual and reproductive variables with the risk of endometrial cancer among the European Prospective Investigation into Cancer and Nutrition (EPIC). Among the 302,618 women eligible for the study, 1,017 incident endometrial cancer cases were identified. A reduction in endometrial cancer risk was observed in women with late menarche, early menopause, past OC use, high parity and a shorter time since last full-term pregnancy (FTP). No association was observed for duration of breast feeding after adjustment for number of FTP or for abortion (spontaneous or induced). After mutual adjustment, late age at menarche, early age at menopause and duration of OC use showed similar risk reductions of 7-8% per year of menstrual life, whereas the decreased risk associated with cumulative duration of FTPs was stronger (22% per year). In conclusion, our findings confirmed a reduction in risk of endometrial cancer with factors associated with a lower cumulative exposure to estrogen and/or higher exposure to progesterone, such as increasing number of FTPs and shorter menstrual lifespan and, therefore, support an important role of hormonal mechanisms in endometrial carcinogenesis.
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