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  • 1
    Abstract: OBJECTIVE: To identify reproductive, lifestyle, hormonal, and other correlates of circulating antimullerian hormone (AMH) concentrations in mostly late premenopausal women. DESIGN: Cross-sectional study. SETTING: Not applicable. PATIENT(S): A total of 671 premenopausal women not known to have cancer. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Concentrations of AMH were measured in a single laboratory using the picoAMH ELISA. Multivariable-adjusted median (and interquartile range) AMH concentrations were calculated using quantile regression for several potential correlates. RESULT(S): Older women had significantly lower AMH concentrations (〉/=40 [n = 444] vs. 〈35 years [n = 64], multivariable-adjusted median 0.73 ng/mL vs. 2.52 ng/mL). Concentrations of AMH were also significantly lower among women with earlier age at menarche (〈12 [n = 96] vs. 〉/=14 years [n = 200]: 0.90 ng/mL vs. 1.12 ng/mL) and among current users of oral contraceptives (n = 27) compared with never or former users (n = 468) (0.36 ng/mL vs. 1.15 ng/mL). Race, body mass index, education, height, smoking status, parity, and menstrual cycle phase were not significantly associated with AMH concentrations. There were no significant associations between AMH concentrations and androgen or sex hormone-binding globulin concentrations or with factors related to blood collection (e.g., sample type, time, season, and year of blood collection). CONCLUSION(S): Among premenopausal women, lower AMH concentrations are associated with older age, a younger age at menarche, and currently using oral contraceptives, suggesting these factors are related to a lower number or decreased secretory activity of ovarian follicles.
    Type of Publication: Journal article published
    PubMed ID: 28366409
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  • 2
    Keywords: EXPOSURE ; BIOMARKERS ; BREAST ; HUMANS ; smoking ; VALIDITY ; ENDOMETRIAL ; HEMOGLOBIN ADDUCTS ; glycidamide
    Abstract: Acrylamide, classified in 1994 by IARC as 'probably carcinogenic' to humans, was discovered in 2002 in some heat-treated, carbohydrate-rich foods. The association between dietary acrylamide intake and epithelial ovarian cancer risk (EOC) has been previously studied in one case-control and three prospective cohort studies which obtained inconsistent results, and could not further examine histological subtypes other than serous EOC. The present study was carried out in the European Prospective Investigation into Cancer and Nutrition (EPIC) sub-cohort of women (n=325,006). Multivariate Cox proportional hazards models were used to assess the association between questionnaire-based acrylamide intake and EOC risk. Acrylamide was energy-adjusted using the residual method, and was evaluated both as a continuous variable (per 10microg/day) and in quintiles; when subgroups by histological EOC subtypes were analyzed, acrylamide intake was evaluated in quartiles. During a mean follow-up of 11 years, 1,191 incident EOC cases were diagnosed. At baseline, the median acrylamide intake in EPIC was 21.3 mug/day. No associations, and no evidence for a dose-response were observed between energy-adjusted acrylamide intake and EOC risk (HR10microg/day:1.02, 95%CI:0.96-1.09; HRQ5vsQ1:0.97, 95%CI:0.76-1.23). No differences were seen when invasive EOC subtypes (582 serous, 118 endometrioid, and 79 mucinous tumors) were analyzed separately. This study did not provide evidence that acrylamide intake, based on food intake questionnaires, was associated with risk for EOC in EPIC. Additional studies with more reliable estimates of exposure based on biomarkers may be needed.
    Type of Publication: Journal article published
    PubMed ID: 25300475
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  • 3
    Keywords: EXPOSURE ; BREAST ; VALIDITY ; QUESTIONNAIRE ; OVARIAN
    Abstract: BACKGROUND: Three prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The objective of this study was to evaluate the association between acrylamide intake and EC risk: for overall EC, for type-I EC, and in never smokers and never users of oral contraceptives (OCs). Smoking is a source of acrylamide, and OC use is a protective factor for EC risk. METHODS: Cox regression was used to estimate hazard ratios (HRs) for the association between acrylamide intake and EC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Acrylamide intake was estimated from the EU acrylamide monitoring database, which was matched with EPIC questionnaire-based food consumption data. Acrylamide intake was energy adjusted using the residual method. RESULTS: No associations were observed between acrylamide intake and overall EC (n=1382) or type-I EC risk (n=627). We observed increasing relative risks for type-I EC with increasing acrylamide intake among women who both never smoked and were non-users of OCs (HRQ5vsQ1: 1.97, 95% CI: 1.08-3.62; likelihood ratio test (LRT) P-value: 0.01, n=203). CONCLUSIONS: Dietary intake of acrylamide was not associated with overall or type-I EC risk; however, positive associations with type I were observed in women who were both non-users of OCs and never smokers.
    Type of Publication: Journal article published
    PubMed ID: 24937665
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  • 4
    Keywords: carcinoma ; HISTORY ; REPRODUCIBILITY ; POSTMENOPAUSAL WOMEN ; PREMENOPAUSAL WOMEN ; STEROID-HORMONES ; PERIOD ; PLASMA PROLACTIN
    Abstract: INTRODUCTION: The relationship between circulating prolactin and invasive breast cancer has been investigated previously, but the association between prolactin levels and in situ breast cancer risk has received less attention. METHODS: We analysed the relationship between pre-diagnostic prolactin levels and the risk of in situ breast cancer overall, and by menopausal status and use of postmenopausal hormone therapy (HT) at blood donation. Conditional logistic regression was used to assess this association in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, including 307 in situ breast cancer cases and their matched control subjects. RESULTS: We found a significant positive association between higher circulating prolactin levels and risk of in situ breast cancer among all women [pre-and postmenopausal combined, ORlog2 = 1.35 (95%CI 1.04-1.76), Ptrend = 0.03]. No statistically significant heterogeneity was found between prolactin levels and in situ cancer risk by menopausal status (Phet = 0.98) or baseline HT use (Phet = 0.20), although the observed association was more pronounced among postmenopausal women using HT compared to non-users (Ptrend = 0.06 vs Ptrend = 0.35). In subgroup analyses, the observed positive association was strongest in women diagnosed with in situ breast tumors 〈4 years compared to 〉/=4 years after blood donation (Ptrend = 0.01 vs Ptrend = 0.63; Phet = 0.04) and among nulliparous women compared to parous women (Ptrend = 0.03 vs Ptrend = 0.15; Phet = 0.07). CONCLUSIONS: Our data extends prior research linking prolactin and invasive breast cancer to the outcome of in situ breast tumours and shows that higher circulating prolactin is associated with increased risk of in situ breast cancer.
    Type of Publication: Journal article published
    PubMed ID: 25887963
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  • 5
    Keywords: BREAST-CANCER ; PATTERNS ; AGE ; nutrition ; METAANALYSIS ; pooled analysis ; FAMILY-HISTORY ; TUBAL-LIGATION ; HYSTERECTOMY ; ASSOCIATION CONSORTIUM
    Abstract: BACKGROUND: Ovarian cancer has a high case-fatality ratio, largely due to late diagnosis. Epidemiologic risk prediction models could help identify women at increased risk who may benefit from targeted prevention measures, such as screening or chemopreventive agents. METHODS: We built an ovarian cancer risk prediction model with epidemiologic risk factors from 202 206 women in the European Prospective Investigation into Cancer and Nutrition study. RESULTS: Older age at menopause, longer duration of hormone replacement therapy, and higher body mass index were included as increasing ovarian cancer risk, whereas unilateral ovariectomy, longer duration of oral contraceptive use, and higher number of full-term pregnancies were decreasing risk. The discriminatory power (overall concordance index) of this model, as examined with five-fold cross-validation, was 0.64 (95% confidence interval (CI): 0.57, 0.70). The ratio of the expected to observed number of ovarian cancer cases occurring in the first 5 years of follow-up was 0.90 (293 out of 324, 95% CI: 0.81-1.01), in general there was no evidence for miscalibration. CONCLUSION: Our ovarian cancer risk model containing only epidemiological data showed modest discriminatory power for a Western European population. Future studies should consider adding informative biomarkers to possibly improve the predictive ability of the model.
    Type of Publication: Journal article published
    PubMed ID: 25742479
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  • 6
    Keywords: hormone ; WOMEN ; CLINICAL-TRIALS ; physiology ; insulin ; METAANALYSIS ; GROWTH-FACTOR-I ; ANTAGONISTS ; INTRAUTERINE GROWTH ; INHIBIT GROWTH
    Abstract: Insulin-like growth factor-I (IGF-I) signaling may promote ovarian tumor development by exerting mitotic, antiapoptotic and proangiogenic effects. During pregnancy, maternal production of IGF-I is regulated by placental growth hormone (GH). Parity is an established protective factor for ovarian cancer, however, no prior study has evaluated placental GH and IGF-I in pregnancy and epithelial ovarian cancer (EOC). Prior prospective studies on the association between IGF-I and EOC in nonpregnant populations were inconclusive and did not address associations in subtypes of EOC. Among members of the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort, we identified 1,045 EOC cases, diagnosed after recruitment (1975-2008) and before March 2011 and 2,658 individually matched controls. Placental GH and IGF-I were measured in serum from the last pregnancy before EOC diagnosis or selection as control. We used conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for tertiles and a doubling of hormone concentrations. Higher IGF-I was associated with a nonsignificant decrease in risk for invasive [ORT3 vs. T1 : 0.79 (0.62-1.02); ptrend = 0.07] and endometrioid tumors [ORT3 vs. T1 : 0.55 (0.28-1.07); ptrend = 0.07]. The protective association between higher IGF-I levels and risk of invasive EOC was stronger in analyses limited to women aged 〈55 years at diagnosis [ORT3 vs. T1 : 0.74 (0.57-0.96); ptrend = 0.03]. Our study provides the first data on placental GH and IGF-I in pregnancy and EOC risk overall and by subtype. Our data suggest higher IGF-I levels in pregnancy may be associated with lower risk of invasive and endometrioid EOC.
    Type of Publication: Journal article published
    PubMed ID: 25516257
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  • 7
    Keywords: AGE ; OBESITY ; nutrition ; ENDOMETRIAL CANCER
    Abstract: Whether risk factors for epithelial ovarian cancer (EOC) differ by subtype (i.e., dualistic pathway of carcinogenesis, histologic subtype) is not well understood; however, data to date suggest risk factor differences. We examined associations between reproductive and hormone-related risk factors for EOC by subtype in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 334,126 women with data on reproductive and hormone-related risk factors (follow-up: 1992-2010), 1,245 incident cases of EOC with known histology and invasiveness were identified. Data on tumor histology, grade, and invasiveness, were available from cancer registries and pathology record review. We observed significant heterogeneity by the dualistic model (i.e., type I [low grade serous or endometrioid, mucinous, clear cell, malignant Brenner] vs. type II [high grade serous or endometrioid]) for full-term pregnancy (phet = 0.02). Full-term pregnancy was more strongly inversely associated with type I than type II tumors (ever vs. never: type I: relative risk (RR) 0.47 [95% confidence interval (CI): 0.33-0.69]; type II, RR: 0.81 [0.61-1.06]). We observed no significant differences in risk in analyses by major histologic subtypes of invasive EOC (serous, mucinous, endometrioid, clear cell). None of the investigated factors were associated with borderline tumors. Established protective factors, including duration of oral contraceptive use and full term pregnancy, were consistently inversely associated with risk across histologic subtypes (e.g., ever full-term pregnancy: serous, RR: 0.73 [0.58-0.92]; mucinous, RR: 0.53 [0.30-0.95]; endometrioid, RR: 0.65 [0.40-1.06]; clear cell, RR: 0.34 [0.18-0.64]; phet = 0.16). These results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes.
    Type of Publication: Journal article published
    PubMed ID: 25656413
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  • 8
    Abstract: BACKGROUND: In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC). However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of developing cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). METHODS AND FINDINGS: We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45,52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for 〉/=15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95%CI: 0.4-0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7). CONCLUSIONS: Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors.
    Type of Publication: Journal article published
    PubMed ID: 26808155
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  • 9
    Abstract: Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (ER, PR, and HER2), alcohol intake, and MTHFR polymorphisms (677C〉T and 1298A〉C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4-Q1 = 1.26; 95% CI 1.00-1.58; Ptrend = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4-Q1 = 1.29; 95% CI 1.02-1.62; Ptrend = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation. This article is protected by copyright. All rights reserved.
    Type of Publication: Journal article published
    PubMed ID: 27905104
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  • 10
    Abstract: PURPOSE: Acrylamide was classified as 'probably carcinogenic' to humans in 1994 by the International Agency for Research on Cancer. In 2002, public health concern increased when acrylamide was identified in starchy, plant-based foods, processed at high temperatures. The purpose of this study was to identify which food groups and lifestyle variables were determinants of hemoglobin adduct concentrations of acrylamide (HbAA) and glycidamide (HbGA) in 801 non-smoking postmenopausal women from eight countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Biomarkers of internal exposure were measured in red blood cells (collected at baseline) by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) . In this cross-sectional analysis, four dependent variables were evaluated: HbAA, HbGA, sum of total adducts (HbAA + HbGA), and their ratio (HbGA/HbAA). Simple and multiple regression analyses were used to identify determinants of the four outcome variables. All dependent variables (except HbGA/HbAA) and all independent variables were log-transformed (log2) to improve normality. Median (25th-75th percentile) HbAA and HbGA adduct levels were 41.3 (32.8-53.1) pmol/g Hb and 34.2 (25.4-46.9) pmol/g Hb, respectively. RESULTS: The main food group determinants of HbAA, HbGA, and HbAA + HbGA were biscuits, crackers, and dry cakes. Alcohol intake and body mass index were identified as the principal determinants of HbGA/HbAA. The total percent variation in HbAA, HbGA, HbAA + HbGA, and HbGA/HbAA explained in this study was 30, 26, 29, and 13 %, respectively. CONCLUSIONS: Dietary and lifestyle factors explain a moderate proportion of acrylamide adduct variation in non-smoking postmenopausal women from the EPIC cohort.
    Type of Publication: Journal article published
    PubMed ID: 26850269
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