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  • 1
    Keywords: CANCER ; BLOOD ; EXPOSURE ; RISK ; BINDING ; ASSOCIATION ; BREAST ; breast cancer ; BREAST-CANCER ; hormone ; HEALTH ; WOMEN ; DIETARY ; UNITED-STATES ; ALCOHOL ; ALCOHOL-CONSUMPTION ; CONSUMPTION ; EPIC ; nutrition ; QUESTIONNAIRE ; IMMUNOASSAYS ; immunoassay ; LIFE-STYLE FACTORS ; dehydroepiandrosterone ; POSTMENOPAUSAL WOMEN ; SERUM ; ONCOLOGY ; RE ; EPIC PROJECT ; LEVEL ; methods ; PREMENOPAUSAL WOMEN ; SERUM-LEVELS ; alcohol consumption ; PREMENOPAUSAL ; prospective ; BINDING GLOBULIN ; CIRCULATING LEVELS ; intake ; steroids ; HORMONE CONCENTRATIONS ; alcohol intake ; ESTRADIOL LEVELS ; post-menopausal women ; pre-menopausal ; SERUM HORMONE CONCENTRATIONS ; sex steroids
    Abstract: Objective Women with a moderate intake of alcohol have higher concentrations of sex steroids in serum, and higher risk of developing breast cancer, compared to non-drinkers. In the present study, we investigate the relationships between alcohol consumption and serum levels of sex steroids and sex-hormone binding globulin (SHBG) in 790 pre- and 1,291 post-menopausal women, who were part of the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods Serum levels of testosterone (T), androstenedione (Delta(4)), dehydroepiandrosterone sulphate (DHEAS), estrone (E-1), estradiol (E-2) and SHBG were measured by direct immunoassays. Free T (fT) and free E-2 (fE(2)) were calculated according to mass action laws. Current alcohol intake exposure to alcohol was assessed from dietary questionnaires. Results Pre-menopausal women who consumed more than 25 g/day of alcohol had about 30% higher DHEAS, T and fT, 20% higher Delta(4) and about 40% higher E-1, concentrations compared to women who were non-consumers. E-2, fE(2) and SHBG concentrations showed no association with current alcohol intake. In post-menopausal women, DHEAS, fT, T, Delta(4), and E-1 concentrations were between 10% and 20% higher in women who consumed more than 25 g/day of alcohol compared to non-consumers. E-2 or fE(2) were not associated with alcohol intake at all. SHBG levels were about 15% lower in alcohol consumers compared to non-consumers. Conclusion This study supports the hypothesis of an influence of alcohol intake on sex hormone concentrations in blood
    Type of Publication: Journal article published
    PubMed ID: 16933054
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  • 2
    Keywords: CANCER ; GROWTH ; BLOOD ; DENSITY ; COHORT ; RISK ; SAMPLES ; TISSUE ; TIME ; BREAST ; breast cancer ; BREAST-CANCER ; hormone ; HEALTH ; DESIGN ; WOMEN ; cancer risk ; QUANTITATIVE-ANALYSIS ; nutrition ; FACTOR-I ; POSTMENOPAUSAL WOMEN ; SERUM ; FEATURES ; ONCOLOGY ; REGRESSION ; INCREASE ; development ; GROWTH-FACTOR-I ; LEVEL ; biomarker ; analysis ; methods ; SERUM-LEVELS ; PREMENOPAUSAL ; prospective ; IGF-BINDING PROTEIN-3 ; cancer research ; RISK-FACTOR ; CANCER-RISK ; CIRCULATING LEVELS ; IGFBP-3 ; FACTOR SYSTEM ; insulin-like growth factor-I ; MAMMOGRAPHIC DENSITIES
    Abstract: Background: A high proportion of glandular and stromal tissue in the breast (percentage breast density) is a strong risk factor for breast cancer development. Insulin-like growth factor-I (IGF-I) is hypothesized to influence breast cancer risk by increasing breast density. Objectives: We studied the relation between premenopausal circulating IGF-I levels and premenopausal and postmenopausal, absolute nondense and dense area, and percentage breast density as well as changes in these measures over menopause. Design and Methods: Mammograms and blood samples of 684 premenopausal participants of the Prospect-European Prospective Investigation into Cancer and Nutrition cohort were collected at baseline. A second mammogram of these women was collected after they became postmenopausal. Premenopausal IGF-I levels were measured in serum. Premenopausal and postmenopausal breast measures were assessed using a computer-assisted method. Mean values of breast measures were calculated for quartiles of serum IGF-I using linear regression analysis. Results: Women with higher premenopausal IGF-I levels showed a slightly smaller decrease in dense area over menopause (-12.2 cm(2) in the highest versus -12.9 cm(2) in the lowest quartile; P trend = 0.58) and, at the same time, a smaller increase in the nondense (fat) area (P trend = 0.09). Due to the changes over menopause, high premenopausal IGF-I serum levels were associated with lower nondense area (P trend = 0.05), somewhat higher dense area (P trend = 0.66), and consequently higher percentage breast density (P trend = 0.02) after menopause. Conclusion and Discussion: Women with higher premenopausal IGF-I levels have a smaller increase in nondense area and also a slightly smaller decrease in absolute dense area during menopause, resulting in higher breast density after menopause
    Type of Publication: Journal article published
    PubMed ID: 17372240
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  • 3
    Keywords: CANCER ; GROWTH ; GROWTH-FACTOR ; BLOOD ; DENSITY ; COHORT ; NEW-YORK ; RISK ; GENE ; SAMPLE ; SAMPLES ; TISSUE ; primary ; RISK-FACTORS ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; BREAST ; breast cancer ; BREAST-CANCER ; CARE ; DESIGN ; WOMEN ; SNP ; risk factors ; PROSTATE-CANCER ; cancer risk ; RECRUITMENT ; BINDING-PROTEINS ; NETHERLANDS ; POSTMENOPAUSAL WOMEN ; menopause ; SERUM ; ONCOLOGY ; RE ; INCREASE ; SINGLE NUCLEOTIDE POLYMORPHISMS ; SNPs ; GROWTH-FACTOR-I ; ALLELES ; LEVEL ; methods ; HAPLOTYPE ; GENOTYPE DATA ; USA ; PREMENOPAUSAL ; prospective study ; mammographic density ; RISK-FACTOR ; CANCER-RISK ; CIRCULATING LEVELS ; MULTIETHNIC COHORT ; Insulin-Like Growth Factor I ; NOV ; postmenopausal ; quantitative ; block ; breast density ; IGF1 ; breast cancer risk ; NUCLEOTIDE ; APOLIPOPROTEIN-E ISOFORMS ; Prospect-EPIC
    Abstract: Introduction High breast density is one of the strongest known risk factors for developing breast cancer. Insulin-like growth factor I (IGF-I) is a strong mitogen and has been suggested to increase breast cancer risk by increasing the amount of dense tissue in the female breast. Objectives We wanted to investigate the effect of common variation in the IGF-1 gene on serum IGF-I levels and on breast density. Design and methods Mammograms and blood samples of 1,928 premenopausal participants of the Dutch Prospect-EPIC cohort were collected at baseline. Using a haplotype tagging approach, 16 single nucleotide polymorphisms (SNP) from three blocks covering the IGF-1 gene were genotyped in all study participants. Breast density was assessed using a quantitative computer-assisted method. For a subgroup of women, who went through menopause within 5 years after recruitment (n = 656), premenopausal IGF-I levels and additionally postmenopausal breast density were determined. False positive report probabilities (FPRP) for statistically significant relations were calculated using the Wacholder method. Results The minor alleles of five SNPs in block 3 were significantly associated with elevated levels of IGF-I (rs9989002, rs2033178, rs7136446, rs978458, rs6220; P-values: 0.01-0.04). The same SNPs were related with modestly higher percent breast density before menopause and-in the subgroup of women that became postmenopausal during follow-up-with a modestly higher percent breast density after menopause. The most significant result, i.e. the relation between rs6220 and IGF-I levels, had an FPRP 〈 0.5 assuming prior probabilities of 0.01 and higher. Conclusion Common genetic variation in the IGF-1 gene is related to circulating levels of IGF-I, but the relationship with breast density is indecisive
    Type of Publication: Journal article published
    PubMed ID: 18064566
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  • 4
    Keywords: CANCER ; CELLS ; BLOOD ; CELL ; FOLLOW-UP ; INFORMATION ; COHORT ; cohort study ; DISEASE ; DISEASES ; HISTORY ; LONG-TERM ; POPULATION ; RISK ; SAMPLES ; HEART ; RISK-FACTORS ; CYCLE ; ASSOCIATION ; FREQUENCY ; FREQUENCIES ; HEALTH ; PLASMA ; WOMEN ; MEN ; risk factors ; smoking ; COUNTRIES ; COMPONENT ; DATABASE ; PRESSURE ; DIET ; nutrition ; SERUM ; ASSOCIATIONS ; RE ; fat distribution ; development ; EVENTS ; PLASMA-LEVELS ; prospective ; prospective study ; DIETARY ASSESSMENT METHODS ; RISK-FACTOR ; study protocol ; CORONARY-ARTERY-DISEASE ; EPIC heart ; HIGH BLOOD-PRESSURE ; NORFOLK COHORT
    Abstract: EPIC-Heart is the cardiovascular component of the European Prospective Investigation into Cancer and Nutrition ( EPIC), a multi-centre prospective cohort study investigating the relationship between nutrition and major chronic disease outcomes. Its objective is to advance understanding about the separate and combined influences of lifestyle ( especially dietary), environmental, metabolic and genetic factors in the development of cardiovascular diseases by making best possible use of the unusually informative database and biological samples in EPIC. Between 1992 and 2000, 519,978 participants ( 366,521 women and 153,457 men, mostly aged 35 - 70 years) in 23 centres in 10 European countries commenced follow-up for causespecific mortality, cancer incidence and major cardiovascular morbidity. Dietary information was collected with quantitative questionnaires or semi-quantitative food frequency questionnaires, including a 24-h dietary recall sub-study to help calibrate the dietary measurements. Information was collected on physical activity, tobacco smoking, alcohol consumption, occupational history, socio-economic status, and history of previous illnesses. Anthropometric measurements and blood pressure recordings were made in the majority of participants. Blood samples were taken from 385,747 individuals, from which plasma, serum, red cells, and buffy coat fractions were separated and aliquoted for long-term storage. By 2004, an estimated 10,000 incident fatal and non-fatal coronary and stroke events had been recorded. The first cycle of EPIC-Heart analyses will assess associations of coronary mortality with several prominent dietary hypotheses and with established cardiovascular risk factors. Subsequent analyses will extend this approach to non-fatal cardiovascular outcomes and to further dietary, biochemical and genetic factors
    Type of Publication: Journal article published
    PubMed ID: 17295097
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  • 5
    Keywords: CANCER ; PROTEIN ; AGE ; WOMEN ; COUNTRIES ; DIET ; DIETARY ; FAT ; ALCOHOL ; CONSUMPTION ; EPIC ; nutrition ; LIFE-STYLE ; EUROPE ; nutrient intake ; DRINKING ; MASS INDEX ; WEIGHT ; RECALL ; EPIC PROJECT ; ERRORS ; 24-h dietary recall ; ENDB ; EPIC-soft ; ITALIAN WOMEN ; SMOKING-HABITS ; UNITED-STATES ADULTS
    Abstract: Background/objectives: Europe has the highest level of alcohol consumption in the world. As drinking patterns are important determinants of the beneficial and harmful effects of alcohol consumption, we investigated alcohol consumption in relation to nutrient intake, place of consumption, education and body weight in a sample of adults from 10 European countries. Methods: A 24-h dietary recall interview was conducted on 13 025 men and 23 009 women, aged 35-74 years, from 27 centres participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Means and standard errors of alcohol consumption, adjusted for age, were calculated, stratified by gender and centre. Results: In many centres, higher level drinkers (males consuming 424 g of ethanol/day, equivalent to 42 standard drinks and females consuming 412 g of ethanol/day equivalent to 41 standard drink) obtained more energy from fat and protein and less from sugar than did abstainers. The proportion of energy from starch tended to be higher for male and lower for female higher level drinkers than for abstainers. Female higher level drinkers had a lower body mass index than did abstainers, whereas male higher level drinkers generally weighed more. Male higher level drinkers were less educated than abstainers in Mediterranean countries, but were more educated elsewhere. Female higher level drinkers were usually more educated than were abstainers. Outside the home, consumption (both genders) tended to be at friends' homes, particularly among men in Northern and Central Europe, and in bars in Spain. Conclusions: This study reveals clear geographical differences in drinking habits across Europe, and shows that the characteristics of different alcohol consumption categories also vary.
    Type of Publication: Journal article published
    PubMed ID: 19888282
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  • 6
    Keywords: CANCER ; BLOOD ; COHORT ; cohort studies ; RISK ; TIME ; BINDING ; ASSOCIATION ; BREAST ; breast cancer ; BREAST-CANCER ; WOMEN ; OBESITY ; cancer risk ; case-control studies ; BODY ; EPIC ; nutrition ; POSTMENOPAUSAL WOMEN ; insulin ; MASS INDEX ; SERUM ; case-control study ; RE ; INCREASE ; WEIGHT ; WAIST ; ESTROGEN ; LEVEL ; case control studies ; metabolic syndrome ; OVERWEIGHT ; HORMONES ; BMI ; EXTENT ; CANCER-RISK ; BODY-FAT DISTRIBUTION ; hip ; steroids ; FREE ESTRADIOL
    Abstract: In a large case-control study on breast cancer risk and serum hormone concentrations, nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we examined to what extent the relationship of excess body weight with breast cancer risk may be explained by changes in sex steroids. Height, weight, waist and hip circumferences, and serum measurements of testosterone [T], androstenedione [Delta(4)], dehydroepiandrosterone sulphate [DHEAS], estradiol [E-2], estrone [E-1] and sex-hormone binding globulin [SHBG] were available for 613 breast cancer cases, and 1,139 matched controls, who were all menopausal at the time of blood donation. Free T [fT] and free E-2 [fE(2)] were calculated using mass action equations. Breast cancer risk was related to body mass index (BMI) (RR = 1.11 [0.99-1.25], per 5 kg/m(2) increase in BMI), and waist (RR = 1.12 [1.02-1.24], per 10 cm increase) and hip circumferences (RR = 1.14 [1.02-1.27], per 10 cm increase). The increase in breast cancer risk associated with adiposity was substantially reduced after adjustment for any estrogens, especially for fE(2) (from 1.11 [0.99-1.25] to 0.99 [0.87-1.12], from 1.12 [1.02-1.24] to 1.02 [0.92-1.14] and from 1.14 [1.02-1.27] to 1.05 [0.93-1.18] for BMI, waist and hip circumferences, respectively). A modest attenuation in excess risk was observed after adjustment for fT, but the remaining androgens had little effect on the association of body adiposity with breast cancer. Our data indicate that the relationship of adiposity with breast cancer in postmenopausal women could be partially explained by the increases in endogenous estrogens, and by a decrease in levels of SHBG. (c) 2005 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 16385576
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  • 7
    Keywords: CANCER ; human ; screening ; COHORT ; cohort studies ; cohort study ; EXPOSURE ; NEW-YORK ; TIME ; IMPACT ; primary ; BIOLOGY ; CYCLE ; ASSOCIATION ; BREAST ; breast cancer ; BREAST-CANCER ; PATTERNS ; EXPERIENCE ; DESIGN ; AGE ; WOMEN ; NETHERLANDS ; PROJECT ; BREAST-CANCER RISK ; menopause ; CHILDHOOD ; PATTERN ; MENSTRUAL-CYCLE ; WEIGHT ; INTERVAL ; LONG ; USA ; menarche ; odds ratio ; caloric restriction ; MEDICINE ; CYCLES ; DOM-PROJECT ; famine ; FECUNDITY ; menstrual cycle ; REPRODUCTIVE FUNCTION
    Abstract: Objective: To investigate the relation between exposure to the 1944-45 Dutch famine and concurrent and subsequent menstrual disturbances. Design: Cohort study. Setting: Doorlopend Onderzoek Mammacarcinoom, breast cancer screening project, Utrecht, the Netherlands. Patient(s): Between 1983 and 1986, approximately 12,500 women (born 1911-41) reported their individual famine experiences. Main Outcome Measure(s): irregular menstruation during the famine; time to regular menses after menarche, and menstrual patterns in adulthood after childhood famine. Result(s): The famine had a direct impact on menstruation. The odds ratio (OR) of concurrent irregular menses in severely versus unexposed women was 8.85 (95% confidence interval [0], 7.31-10.70). Women exposed to severe famine before menarche were 1.51 (95% Cl, 1. 15-1.98) times more likely to experience irregular menses for a prolonged time after menarche compared with the unexposed. This association was stronger in women with an early menarche. When the menstrual pattern was assessed in adulthood by menstrual diaries, a nonsignificant tendency of increased irregularity (OR, 1. 13; 95% Cl, 0.82-1.54) and regular but long menstrual cycles (OR, 1.41; 95% CI, 0.89-2.23) was observed in women exposed to severe famine. Conclusion(S): Famine relates to concurrent menstrual irregularity, and exposure in childhood seems to affect the subsequent menstrual pattern. (Fertil Steril (R) 2007;88(Suppl 2):1101-7. (C)2007 by American Society for Reproductive Medicine.)
    Type of Publication: Journal article published
    PubMed ID: 17544416
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  • 8
    Abstract: Mammographic density is strongly related to increased breast cancer risk. Accumulating evidence indicates that a role for the IGF-pathway in mammographic density and breast cancer development. Here, we investigate whether common genetic variation in this pathway influences insulin-like growth factor-I (IGF-I) levels and mammographic density. In 1,916 premenopausal women within the Prospect-EPIC cohort, we examined associations of 14 haplotype tagging SNPs in the ALS, IGFBP1, and IGFBP3 genes with IGF-I circulating levels and mammographic density. In 657 women, who became postmenopausal during follow-up, we investigated how these SNPs were related with the decrease in density over menopause. Linear regression models were used for statistical analysis. None of the ALS or IGFBP3 SNPs were statistically significantly associated with IGF-I levels or mammographic density. The CC genotype for rs1908751 (IGFBP1) was associated with lower levels of IGF-I (110.9 ng/ml) compared to the CT/TT genotypes (115.7 ng/ml) (P = 0.04). Women with the CC genotype also had lower percent density, although not statistically significantly (P = 0.12). Women carrying the AA genotype for rs1995051 (IGFBP1) showed that borderline significantly lower IGF-I levels (P = 0.06) and significantly lower mammographic density (40.3% compared to 43.5% in the GG/GA genotypes; P = 0.05). No relationships were found for any of the SNPs in relation with changes in breast density over menopause. These findings suggest that common genetic variation in the IGFBP1 gene is weakly related to IGF-I levels and mammographic density. Our results do not provide support for such a role of genetic variants in the IGFBP3 and ALS genes
    Type of Publication: Journal article published
    PubMed ID: 20155489
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  • 9
    Keywords: CANCER ; GROWTH ; GROWTH-FACTOR ; tumor ; BLOOD ; DIAGNOSIS ; RISK ; TIME ; REDUCTION ; BINDING ; ASSOCIATION ; BREAST ; breast cancer ; BREAST-CANCER ; AGE ; WOMEN ; COLORECTAL-CANCER ; SWEDEN ; cancer risk ; Jun ; INVOLVEMENT ; case-control studies ; EPIC ; nutrition ; FACTOR-I ; insulin ; YOUNG ; SERUM ; IGF-I ; case-control study ; RE ; INCREASE ; METAANALYSIS ; GROWTH-FACTOR-I ; LEVEL ; case control studies ; INTERVAL ; FACTOR (IGF)-I ; prospective ; prospective study ; odds ratio ; CANCER-RISK ; CIRCULATING LEVELS ; C-PEPTIDE ; IGFBP-3 ; NORTHERN ; FACTOR-BINDING-PROTEINS
    Abstract: Blood concentrations of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) have recently been associated with breast cancer risk, notably in women who developed breast cancer at a young age. Prospective studies published so far, however, were relatively small and odds ratio (OR) estimates imprecise. We present the results of a large prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition on total IGIF-I, IGFBP-3 and breast cancer risk including 1081 incident cases of invasive breast cancer and 2098 matched control subjects. Increasing IGF-I and IGFBP-3 concentrations were associated with a significant increase in breast cancer risk in women who developed breast cancer after 50 years of age (highest vs lowest quintile OR 1.38 (95% confidence interval (CI) 1.02-1.86), P = 0.01, and 1.44 (95% CI 1.04-1.98), P = 0.01, respectively), but no relationship was observed in younger women (OR = 1.03 (95% CI 0.60-1.77), P = 0.81 for IGF-I, and OR = 0.92 (95% CI 0.50-1.70), P = 0.69 for IGFBP-3). There was, however, significant heterogeneity in the relationship of breast cancer with serum IGF-I and IGFBP-3 levels depending on the time interval between blood donation and tumor diagnosis. A reduction in breast cancer risk with increasing IGF-I concentrations was observed in cases with a diagnosis of cancer less than 2 years after blood donation, (OR = 0.76 (95% CI 0.57-1.03)), while an increase in risk was observed for women with a later diagnosis (above or equal to two years after blood collection, OR = 1.51 (95% CI 1.19-1.91)). A similar pattern was observed for IGFBP-3. This study confirms previous findings for an association of serum IGF-I and IGFBP-3 concentrations with breast cancer risk, particularly for women with a later diagnosis of cancer, but it does not support the hypothesis of an involvement of IGF-I in younger women
    Type of Publication: Journal article published
    PubMed ID: 16728585
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  • 10
    ISSN: 1573-7284
    Keywords: Atherosclerosis ; Cardiovascular disease ; Cohort study ; Risk factors ; Secondary prevention
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The Second Manifestations of ARTerial disease (SMART) study is a single-centre prospective cohort study among patients, newly referred to the hospital with (1) clinically manifest atherosclerotic vessel disease, or (2) marked risk factors for atherosclerosis. The first objectives of the SMART study are to determine the prevalence of concomitant arterial disease at other sites, and risk factors in patients presenting with a manifestation of arterial disease or vascular risk factor and to study the incidence of future cardiovascular events and its predictors in these high-risk patients. At least 1000 patients, aged 18 to 80 years, will undergo baseline examinations, including a questionnaire on cardiovascular disease, height, weight and blood pressure measurements, blood tests for glucose, lipids, creatinine and homocysteine, urinary tests for microproteinuria, resting twelve-lead electrocardiogram, ultrasound scanning of the abdominal aorta, kidneys and the carotid arteries, measurements of common carotid intima-media thickness and arterial stiffness, and a treadmill test to assess atherosclerosis of the leg arteries. Abnormal findings are reported to the treating specialist and general practitioner with a treatment suggestion according to current practice guidelines. Recruitment and baseline examinations began in September 1996. All cohort members will be followed for clinical cardiovascular events for a minimum of three years. In the scope of secondary prevention, the study is expected to support the design of solid based screening and treatment programmes and evidence-based cardiovascular medicine to reduce morbidity and mortality, and improve quality of life, in high-risk patients.
    Type of Medium: Electronic Resource
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