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  • 1
    Keywords: ENERGIES ; CANCER ; Germany ; human ; MODEL ; MODELS ; FOLLOW-UP ; COHORT ; EPIDEMIOLOGY ; RISK ; RISK-FACTORS ; ASSOCIATION ; BREAST ; breast cancer ; BREAST-CANCER ; TRIAL ; hormone ; HEALTH ; ENERGY ; AGE ; WOMEN ; HORMONE REPLACEMENT THERAPY ; OBESITY ; risk factors ; COUNTRIES ; cancer risk ; RISK FACTOR ; EPIC ; EPIC study ; European Prospective Investigation into Cancer and Nutrition ; nutrition ; POSTMENOPAUSAL WOMEN ; MASS INDEX ; PH ; WEIGHT ; body weight ; fat distribution ; HEIGHT ; ADIPOSITY ; breast neoplasm ; HORMONE-REPLACEMENT THERAPY ; METAANALYSIS
    Abstract: The evidence for anthropometric factors influencing breast cancer risk is accumulating, but uncertainties remain concerning the role of fat distribution and potential effect modifiers. We used data from 73,542 premenopausal and 103,344 postmenopausal women from 9 European countries, taking part in the EPIC study. RRs from Cox regression models were calculated, using measured height, weight, BMI and waist and hip circumferences; categorized by cohort wide quintiles; and expressed as continuous variables, adjusted for study center, age and other risk factors. During 4.7 years of follow-up, 1,879 incident invasive breast cancers were identified. In postmenopausal women, current HRT modified the body size-breast cancer association. Among nonusers, weight, BMI and hip circumference were positively associated with breast cancer risk (all P-trend less than or equal to 0.002); obese women (BMI 〉 30) had a 31% excess risk compared to women with BMI 〈 25. Among HRT users, body measures were inversely but nonsignificantly associated with breast cancer. Excess breast cancer risk with HRT was particularly evident among lean women. Pooled RRs per height increment of 5 cm were 1.05 (95% CI 1.00-1.16) in premenopausal and 1.10 (95% CI 1.05-1.16) in postmenopausal women. Among premenopausal women, hip circumference was the only other measure significantly related to breast cancer (P-trend = 0.03), after accounting for BMI. In postmenopausal women not taking exogenous hormones, general obesity is a significant predictor of breast cancer, while abdominal fat assessed as waist-hip ratio or waist circumference was not related to excess risk when adjusted for BMI. Among premenopausal women, weight and BMI showed nonsignificant inverse associations with breast cancer. (C) 2004 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 15252848
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  • 2
    Keywords: RECEPTOR ; CANCER ; GROWTH ; GROWTH-FACTOR ; proliferation ; tumor ; CELL-PROLIFERATION ; PATHWAY ; RISK ; GENE ; GENES ; PROTEIN ; TUMORS ; RELEASE ; PATIENT ; BINDING ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; VARIANTS ; BREAST ; breast cancer ; BREAST-CANCER ; hormone ; COLORECTAL-CANCER ; PROSTATE-CANCER ; cancer risk ; case-control studies ; SOMATOSTATIN ; CANCER PATIENTS ; nutrition ; FACTOR-I ; BINDING PROTEIN ; SERUM ; SINGLE ; IGF-I ; BINDING-PROTEIN ; case-control study ; ASSOCIATIONS ; RE ; VARIANT ; SINGLE NUCLEOTIDE POLYMORPHISMS ; cell proliferation ; development ; GROWTH-FACTOR-I ; BINDING PROTEIN-3 ; LEVEL ; case control studies ; GENOTYPE DATA ; FACTOR (IGF)-I ; PREMENOPAUSAL WOMEN ; IGFBP3 ; insulin-like growth factor ; PLASMA-LEVELS ; SERUM-LEVELS
    Abstract: Insulin-like growth factor-I (IGF-I) stimulates cell proliferation and can enhance the development of tumors in different organs. Epidemiologic studies have shown that an elevated level of circulating IGF-I is associated to increased risk of breast cancer as well as other cancers. Genetic variants affecting the release or biological action of growth hormone (GH), the main stimulator of IGF-I production, may predict circulating levels of IGF-I and have an effect on cancer risk. We tested this hypothesis with a large case-control study of 807 breast cancer patients and 1,588 matched control subjects nested within the European Prospective Investigation into Cancer and Nutrition. We genotyped 22 common single nucleotide polymorphisms in 10 genes involved in GH production and action (GHRH, GHRHR, SST, SSTR1-SSTR5, POU1F1, and GH1), and in parallel, we measured serum levels of IGF-I and IGFBP-3, its major binding protein, in samples of cases and controls. SST and SSTR2 polymorphisms showed weak but statistically significant associations with breast cancer risk. SSTR5 polymorphisms were associated with IGF-I levels, whereas one polymorphism in GHRHR and one in POU1F1 were associated with IGFBP-3 levels. Our conclusion is that common genetic variation in the GH synthesis pathway, as measured by single nucleotide polymorphisms selected in the present study, is not a major determinant of IGF-I and IGFBP-3 circulating levels, and it does not play a major role in altering breast cancer risk
    Type of Publication: Journal article published
    PubMed ID: 16214911
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  • 3
    Keywords: CANCER ; BLOOD ; MODEL ; MODELS ; COHORT ; RISK ; RISKS ; PATIENT ; RISK-FACTORS ; BINDING ; CYCLE ; ASSOCIATION ; BREAST ; breast cancer ; BREAST-CANCER ; hormone ; WOMEN ; risk factors ; cancer risk ; case-control studies ; EPIC ; nutrition ; ESTRADIOL ; SERUM ; SINGLE ; DEFICIENCY ; case-control study ; ASSOCIATIONS ; RE ; MAMMARY-GLAND ; ESTROGEN ; case control studies ; INTERVAL ; TESTS ; RANDOMIZED CONTROLLED-TRIAL ; PREMENOPAUSAL WOMEN ; SERUM-LEVELS ; ADRENAL ANDROGENS ; ESTROGEN PLUS PROGESTIN ; FEMALE NOBLE RATS ; HEALTHY POSTMENOPAUSAL WOMEN ; HORMONE LEVELS ; ONE-YEAR PERIOD ; REPLACEMENT THERAPY
    Abstract: Background. Contrasting etiologic hypotheses about the role of endogenous sex steroids in breast cancer development among premenopausal women implicate ovarian androgen excess and progesterone deficiency, estrogen excess, estrogen and progesterone excess, and both an excess or lack of adrenal androgens (dehydroepiandrosterone [DHEA] or its sulfate [DHEAS]) as risk factors. We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort to examine associations among premenopausal serum concentrations of sex steroids and subsequent breast cancer risk. Methods: Levels of DHEAS, (Delta 4-)androstenedione, testosterone, and sex hormone binding globulin (SHBG) were measured in single prediagnostic serum samples from 370 premenopausal women who subsequently developed breast cancer (case patients) and from 726 matched cancer-free control subjects. Levels of progesterone, estrone, and estradiol were also measured for the 285 case patients and 555 matched control subjects who had provided information about the day of menstrual cycle at blood donation. Conditional logistic regression models were used to estimate relative risks of breast cancer by quartiles of hormone concentrations. All statistical tests were two-sided. Results: Increased risks of breast cancer were associated with elevated serum concentrations of testosterone (odds ratio [OR] for highest versus lowest quartile = 1.73, 95% confidence interval [CI] = 1.16 to 2.57; P-trend =.01), androstenedione (OR for highest versus lowest quartile = 1.569 95% CI = 1.05 to 2.32; P-trend =.01), and DHEAS (OR for highest versus lowest quartile = 1.48, 95% CI = 1.02 to 2.14; P-trend =.10) but not SHBG. Elevated serum progesterone concentrations were associated with a statistically significant reduction in breast cancer risk (OR for highest versus lowest quartile = 0.61, 95% CI = 0.38 to 0.98; P-trend =.06). The absolute risk of breast cancer for women younger than 40 followed up for 10 years was estimated at 2.6% for those in the highest quartile of serum testosterone versus 1.5% for those in the lowest quartile; for the highest and lowest quartiles of progesterone, these estimates were 1.7% and 2.6%, respectively. Breast cancer risk was not statistically significantly associated with serum levels
    Type of Publication: Journal article published
    PubMed ID: 15900045
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  • 4
    Keywords: CANCER ; tumor ; Germany ; human ; MODEL ; MODELS ; COHORT ; MORTALITY ; RISK ; ASSOCIATION ; ovarian cancer ; OVARIAN-CANCER ; COUNTRIES ; cancer risk ; DIETARY ; CONSUMPTION ; nutrition ; QUESTIONNAIRE ; questionnaires ; VEGETABLES ; NUTRIENTS ; carotenoids ; DIETARY FACTORS ; DETERMINANTS ; SUBTYPE ; FRUITS ; PART ; PARTICIPANTS ; CANCER INCIDENCE ; ALLIUM VEGETABLES ; FOOD GROUPS
    Abstract: Objective: The association between consumption of fruit and vegetables and risk of ovarian cancer is still unclear from a prospective point of view. Methods: Female participants (n = 325,640) of the European Prospective Investigation into Cancer and Nutrition study, free of any cancer at baseline, were followed on average for 6.3 years to develop ovarian cancer. During 2,049,346 person-years, 581 verified cases of primary, invasive epithelial ovarian cancer were accrued. Consumption of fruits and vegetables as well as subgroups of vegetables, estimated from validated dietary questionnaires and calibrated thereafter, was related to ovarian cancer incidence in multivariable hazard regression models. Histologic subtype specific analyses were done. Results: Total intake of fruit and vegetables, separately or combined, as well as subgroups of vegetables (fruiting, root, leafy vegetables, cabbages) was unrelated to risk of ovarian cancer. A high intake of garlic/onion vegetables was associated with a borderline significant reduced risk of this cancer. The examination by histologic subtype indicated some differential effects of fruit and vegetable intake on ovarian cancer risk. Conclusion: Overall, a high intake of fruits and vegetables did not seem to protect from ovarian cancer. Garlic/onion vegetables may exert a beneficial effect. The study of the histologic subtype of the tumor warrants further investigation
    Type of Publication: Journal article published
    PubMed ID: 16284374
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  • 5
    Keywords: CANCER ; Germany ; human ; MODEL ; COHORT ; RISK ; ASSOCIATION ; MEN ; COUNTRIES ; DIETARY ; ALCOHOL ; CONSUMPTION ; EPIC ; nutrition ; VEGETABLES ; CALIBRATION ; RELATIVE RISK ; REGRESSION ; ASSOCIATIONS ; LEVEL ; INTERVAL ; FRUITS ; fruits and vegetables ; prospective ; prospective study ; RECOMMENDATIONS ; EUROPEAN COUNTRIES ; CANCERS ; VARIABLES ; root vegetables ; SUBGROUPS ; upper aero-digestive cancer
    Abstract: Epidemiologic studies suggest that a high intake of fruits and vegetables is associated with decreased risk of cancers of the upper aero-digestive tract. We studied data from 345,904 subjects of the prospective European Investigation into Cancer and Nutrition (EPIC) recruited in seven European countries, who had completed a dietary questionnaire in 1992-1998. During 2,182,560 person years of observation 352 histologically verified incident squamous cell cancer (SCC) cases (255 males; 97 females) of the oral cavity, pharynx, larynx, and esophagus were identified. Linear and restricted cubic spline Cox regressions were fitted on variables of intake of fruits and vegetables and adjusted for potential confounders. We observed a significant inverse association with combined total fruits and vegetables intake (estimated relative risk (RR) = 0.91; 95% confidence interval (95% CI) 0.83-1.00 per 80 g/d of consumption), and nearly significant inverse associations in separate analyses with total fruits and total vegetables intake (RR: 0.97 (95% CI: 0.92-1.02) and RR = 0.89 (95% CI: 0.78-1.02) per 40 g/d of consumption). Overall, vegetable subgroups were not related to risk with the exception of intake of root vegetables in men. Restricted cubic spline regression did not improve the linear model fits except for total fruits and vegetables and total fruits with a significant decrease in risk at low intake levels (〈 120 g/d) for fruits. Dietary recommendations should consider the potential benefit of increasing fruits and vegetables consumption for reducing the risk of cancers of the upper aero-digestive tract, particularly at low intake
    Type of Publication: Journal article published
    PubMed ID: 16841263
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  • 6
    Keywords: ORAL-CONTRACEPTIVES ; PREVALENCE ; BREAST-CANCER RISK ; menopause ; DETERMINANTS ; RANDOMIZED CONTROLLED-TRIAL ; ESTROGEN PLUS PROGESTIN ; HEALTHY POSTMENOPAUSAL WOMEN ; EPIC-Heidelberg ; correlates ; hormone replacement therapy (HRT) ; EPIC-Potsdam ; UP HERS-II ; ESTROGEN/PROGESTIN REPLACEMENT ; DISEASE OUTCOMES ; SWEDISH WOMEN
    Abstract: Objective: To describe the prevalence and to assess type and indicators of hormone replacement therapy (HRT) use in the two German EPIC-cohorts. Methods: Approximately 30,000 women predominantly aged 35-65 years were recruited in EPIC-Heidelberg and EPIC-Potsdam between 1994 and 1998. Information on diet and lifestyle, medical history and use of hormone therapy was collected at recruitment. Prevalence and type of HRT-regime was described and logistic regression models used to examine correlates of HRT-use.Results: Among women aged 45-64 years, 37.9% in Heidelberg and 35.8% in Potsdam were current HRT users. Among cur-rent users without bilateral oophorectomy, 40,5% in Heidelberg and 23.7% in Potsdam used HRT for at least 5 years. Most women in Heidelberg were taking cyclic combined or estrogen monotherapy, whereas in Potsdam both continuous combined and cyclic combined therapies were most frequently used. In both centres, older age, ever use of oral contraceptives, and alcohol consumption were indicators for both current and ever HRT-use. HRT-use was less frequent in obese women as compared to women with lower BMI. In Potsdam, but not in Heidelberg, higher education and current smoking were associated with HRT-use.Conclusion: In both German EPIC-cohorts, the prevalence of medication with HRT is high compared to other European countries. Types of exogenous hormones used differed by centre. Various reproductive and lifestyle characteristics were identified as correlates of HRT-use. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
    Type of Publication: Journal article published
    PubMed ID: 17194554
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  • 7
    Keywords: CANCER ; BLOOD ; Germany ; RISK ; METABOLISM ; ASSOCIATION ; BREAST-CANCER ; DESIGN ; NUMBER ; AGE ; WOMEN ; REPRODUCIBILITY ; etiology ; cancer risk ; EPIC ; nutrition ; ESTRADIOL ; POSTMENOPAUSAL WOMEN ; SERUM ; ONCOLOGY ; REGRESSION ; ESTROGEN ; LEVEL ; analysis ; PHASE ; PREMENOPAUSAL ; TESTOSTERONE ; prospective ; STEROID-HORMONES ; VARIABLES ; CANCER-RISK ; BINDING GLOBULIN ; ENGLAND ; steroids ; SEX-HORMONES ; postmenopausal ; androgens ; FREE TESTOSTERONE ; ESTROGENS
    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% Cl 1.20-3.60; P=0.001) for estradiol, and 1.66 (95% Cl 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% Cl 0.88-2.36; P=0.05) and 2.05 (95% Cl 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% Cl 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
    Type of Publication: Journal article published
    PubMed ID: 18509001
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  • 8
    Keywords: CANCER ; GROWTH ; PROTEIN ; BINDING ; BREAST ; breast cancer ; BREAST-CANCER ; hormone ; lifestyle ; ASSAY ; DESIGN ; WOMEN ; case-control studies ; BODY ; body mass index ; QUESTIONNAIRE ; FACTOR-I ; LIFE-STYLE ; POSTMENOPAUSAL WOMEN ; BINDING PROTEIN ; MASS INDEX ; SERUM ; IGF-I ; case-control study ; REGRESSION ; REPRODUCTIVE FACTORS ; RE ; WEIGHT ; PHYSICAL-ACTIVITY ; HEIGHT ; GROWTH-FACTOR-I ; WAIST ; LEVEL ; case control studies ; ASSAYS ; FACTOR (IGF)-I ; PREMENOPAUSAL WOMEN ; SERUM-LEVELS ; HORMONES ; BMI ; cross-sectional studies ; CIRCULATING LEVELS ; IGFBP-3 ; hip ; ENDOGENOUS HORMONES ; FACTOR BINDING-PROTEIN-3 CONCENTRATIONS ; HORMONE-BINDING-PROTEIN ; nonlinear ; NUTRITIONAL REGULATION ; WAIST CIRCUMFERENCE ; waist-hip ratio
    Abstract: Objective: To examine the relationship between body mass index (BMI) and waist-hip ratio (WHR) with serum levels of insulin-like growth factor-I (IGF-I), and its binding protein (IGFBP)-3. Design: Cross-sectional study on 2139 women participating in a case-control study on breast cancer and endogenous hormones. Data on lifestyle and reproductive factors were collected by means of questionnaires. Body height, weight, waist and hip circumferences were measured. Serum levels of IGF-I and insulin-like binding protein (IGFBP)-3 were measured by enzyme-linked immunosorbent assays. Adjusted mean levels of IGF-I and IGFBP-3 across quintiles of BMI, waist circumference, and WHR were calculated by linear regression. Results were adjusted for potential confounders associated with IGF-I and IGFBP-3. Results: Adjusted mean serum IGF-I values were lower in women with BMI 〈 22.5 kg/m(2) or BMI 〉 29.2 kg/m(2) compared to women with BMI within this range (P-heterogeneity 〈 0.0001, P-trend = 0.35). Insulin-like growth factor-I was not related to WHR after adjustment for BMI. IGF-binding protein-3 was linearly positively related to waist and WHR after mutual adjustment. The molar ratio IGF-I/IGFBP-3 had a non-linear relation with BMI and a linear inverse relationship with WHR (P-trend = 0.005). Conclusions: Our data confirm the nonlinear relationship of circulating IGF-I to total adiposity in women. Serum IGFBP-3 was positively related to central adiposity. These suggest that bioavailable IGF-I levels could be lower in obese compared to non-obese women and inversely related to central adiposity
    Type of Publication: Journal article published
    PubMed ID: 16552400
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  • 9
    Keywords: CANCER ; INFORMATION ; RISK ; BREAST ; breast cancer ; BREAST-CANCER ; WOMEN ; COUNTRIES ; cancer risk ; EPIC ; nutrition ; RELATIVE RISK ; RE ; INCREASE ; prospective ; CANCER-RISK ; induced abortion ; prospective data ; recall bias ; spontaneous abortion
    Abstract: The role of spontaneous and induced abortion on breast cancer risk is examined among 267,361 women recruited into the European Prospective Investigation into Cancer and nutrition between 1992 and 2000. The data were collected from 20 centers, across 9 countries, and included information on a total of 4,805 women with breast cancer, of whom 1,657 reported having ever had any type of abortion. Overall, the relative risk of breast cancer in women who reported ever having had a spontaneous abortion was not significantly elevated when compared with women who reported never having had such an abortion (RR = 1.07, 95 % CI = 0.99-1.14). However, there was some evidence of a slight increase in the risk of breast cancer among women who reported having had 2 or more spontaneous abortions (1.20,1.07-1.35). The relative risk of breast cancer among women who reported ever having had an induced abortion when compared to women who reported never having had an induced abortion was 0.95 (0.87-1.03). Overall, the findings provide further unbiased evidence of the lack of an adverse effect of induced abortion on breast cancer risk. (c) 2006 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 16646050
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  • 10
    Keywords: CANCER ; GROWTH ; MODELS ; FOLLOW-UP ; COHORT ; RISK ; PROTEIN ; breast cancer ; BREAST-CANCER ; WOMEN ; COLORECTAL-CANCER ; DIET ; CALCIUM ; POSTMENOPAUSAL WOMEN ; GROWTH-FACTOR-I ; ELDERLY-MEN ; FACTOR (IGF)-I ; PREMENOPAUSAL WOMEN ; CIRCULATING LEVELS ; IGFBP-3 ; FACTOR SYSTEM ; VITAMIN-D ; insulin-like growth factor-I ; insulin-like growth factor binding protein-3 ; milk ; NUTRITIONAL FACTORS ; SOMATOMEDIN-C
    Abstract: Objective: The aim of this study was to examine the relationship of diet with serum insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in women. Design: Cross-sectional study. Setting and subjects: The population are 2109 women who were control subjects in a case-control study of breast cancer nested in the European Prospective Investigation into Cancer and Nutrition. Control subjects were randomly chosen among risk sets consisting of female cohort members alive and free of cancer (except non-melanoma skin cancer) at the time of diagnosis of the index case. Matching criteria were age at enrolment, follow-up time, time of the day of blood collection and study centre. Diet was measured through validated questionnaires. Serum hormone concentrations were measured by enzyme-linked immunosorbent assays. The relationship between serum IGF-I, IGFBP-3, and intake of nutrients and foods was explored by linear regression in models adjusted for energy intake, age, body mass index, smoking, physical activity, centre and laboratory batch. Results: Serum IGF-I levels were positively related to protein intake (P-trend 〈 0.001), but not related to energy, fat or carbohydrate intake. Positive relationships were observed with the intake of milk (P-trend = 0.007), calcium (P-trend 〈 0.001), magnesium (P-trend = 0.003), phosphorus (P-trend 〈 0.001), potassium (P-trend = 0.002), vitamin B6 (P-trend = 0.03), vitamin B2 (P-trend = 0.001) and inverse relationships with vegetables (P-trend = 0.02) and beta-carotene (P-trend = 0.02). IGFBP-3 was not related with most of the nutrients and foods in this study. Conclusions: In this population, circulating IGF-I is modestly related with the intake of protein and minerals, and with milk and cheese, while IGFBP-3 does not appear to be related with diet
    Type of Publication: Journal article published
    PubMed ID: 16900085
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