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  • 1
    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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  • 2
    Keywords: Germany ; MODEL ; MODELS ; COHORT ; POPULATION ; TIME ; PATIENT ; ASSOCIATION ; AGE ; WOMEN ; PROSPECTIVE COHORT ; BETA ; DIET ; INDIVIDUALS ; time trends ; TRENDS ; EUROPE ; DENMARK ; BREAST-CANCER RISK ; POSTMENOPAUSAL WOMEN ; STANDARD ; ADULT ; RE ; DETERMINANTS ; BODY-SIZE ; HEIGHT ; PARTICIPANTS ; BIRTH ; body height ; menarche ; SECULAR TRENDS ; URINE ESTROGENS
    Abstract: In the last two centuries, age at menarche has decreased in several European populations, whereas adult height has increased. It is unclear whether these trends have ceased in recent years or how age at menarche and height are related in individuals. In this study, the authors first investigated trends in age at menarche and adult height among 286,205 women from nine European countries by computing the mean age at menarche and height in 5-year birth cohorts, adjusted for differences in socioeconomic status. Second, the relation between age at menarche and height was estimated by linear regression models, adjusted for age at enrollment between 1992 and 1998 and socioeconomic status. Mean age at menarche decreased by 44 days per 5-year birth cohort (beta = -0.12, standard error = 0.002), varying from 18 days in the United Kingdom to 58 days in Spain and Germany. Women grew 0.29 cm taller per 5-year birth cohort (standard error = 0.007), varying from 0.42 cm in Italy to 0.98 cm in Denmark. Furthermore, women grew approximately 0.31 cm taller when menarche occurred 1 year later (range by country: 0.13-0.50 cm). Based on time trends, more recent birth cohorts have their menarche earlier and grow taller. However, women with earlier menarche reach a shorter adult height compared with women who have menarche at a later age
    Type of Publication: Journal article published
    PubMed ID: 16107566
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  • 3
    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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  • 4
    Keywords: CANCER ; tumor ; FOLLOW-UP ; COHORT ; RISK ; RISKS ; TUMORS ; colon ; ASSOCIATION ; ENERGY ; WOMEN ; etiology ; MEN ; COLORECTAL-CANCER ; cancer risk ; COLON-CANCER ; DOSE-RESPONSE ; UNITED-STATES ; BODY ; body mass index ; nutrition ; dietary fiber ; LEISURE-TIME ; physical activity ; RECTAL-CANCER ; MASS INDEX ; ASSOCIATIONS ; colon cancer ; PHYSICAL-ACTIVITY ; INTERVAL ; PARTICIPANTS ; BODY-MASS INDEX ; ENERGY-BALANCE ; prospective ; BMI ; CANCERS ; CANCER-RISK ; ACTIVITY QUESTIONNAIRE ; ANATOMIC SUBSITE ; intake ; LARGE-BOWEL-CANCER ; OCCUPATIONAL RISK
    Abstract: We investigated several aspects of the role of physical activity in colon and rectal cancer etiology that remain unclear in the European Prospective Investigation into Nutrition and Cancer. This cohort of 413,044 men and women had 1,094 cases of colon and 599 cases of rectal cancer diagnosed during an average of 6.4 years of follow-up. We analyzed baseline data on occupational, household, and recreational activity to examine associations by type of activity, tumor subsite, body mass index (BMI), and energy intake. The multivariate hazard ratio for colon cancer was 0.78 [95% confidence interval (95% CI), 0.59-1.03] among the most active participants when compared with the inactive, with evidence of a dose-response effect (P-trend = 0.04). For right-sided colon tumors, the risk was 0.65 (95% CI, 0.43-1.00) in the highest quartile of activity with evidence of a linear trend (P-trend=0.004). Active participants with a BMI under 25 had a risk of 0.63 (95% CI, 0.39-1.01) for colon cancer compared with the inactive. Finally, an interaction between BMI and activity (P-interaction=0.03) was observed for right-sided colon cancers; among moderately active and active participants with a BMI under 25, a risk of 0.38 (95% CI, 0.21-0.68) was found as compared with inactive participants with BMI 〉 30. No comparable decreased risks were observed for rectal cancer for any type of physical activity for any subgroup analyses or interactions considered. We found that physical activity reduced colon cancer risk, specifically for right-sided tumors and for lean participants, but not rectal cancer
    Type of Publication: Journal article published
    PubMed ID: 17164362
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  • 5
    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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  • 6
    Keywords: CANCER ; MODEL ; MODELS ; FOLLOW-UP ; RISK ; METABOLISM ; INDEX ; CARCINOGENESIS ; ASSOCIATION ; BREAST-CANCER ; NO ; hormone ; PLASMA ; NUMBER ; WOMEN ; OBESITY ; cancer risk ; ORAL-CONTRACEPTIVES ; cholesterol ; LIPOPROTEIN ; LOW-DENSITY-LIPOPROTEIN ; case-control studies ; ABNORMALITIES ; BODY ; DIABETES-MELLITUS ; EPIC ; European Prospective Investigation into Cancer and Nutrition ; nutrition ; ENDOMETRIAL CANCER ; RELATIVE RISK ; REGRESSION-MODELS ; CLUSTER ; POSTMENOPAUSAL WOMEN ; MASS INDEX ; MASSES ; BODIES ; ONCOLOGY ; case control study ; case-control study ; REGRESSION ; ASSOCIATIONS ; ENDOMETRIAL ; RE ; INCREASE ; BODY-SIZE ; PHYSICAL-ACTIVITY ; LEVEL ; case control studies ; INTERVAL ; metabolic syndrome ; HORMONES ; prospective ; UNIT ; CANCER-RISK ; C-PEPTIDE ; SET ; case control ; LOGISTIC-REGRESSION ; BODY-MASS ; BODY-MASS-INDEX ; lipid ; HDL-CHOLESTEROL ; LOW-DENSITY ; SERUM-CHOLESTEROL
    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
    Type of Publication: Journal article published
    PubMed ID: 17914105
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  • 7
    Keywords: CANCER ; BLOOD ; Germany ; COHORT ; RISK ; MICE ; ASSOCIATION ; BREAST-CANCER ; hormone ; AGE ; ovarian cancer ; OVARIAN-CANCER ; WOMEN ; cancer risk ; case-control studies ; VALIDITY ; nutrition ; dehydroepiandrosterone ; POSTMENOPAUSAL WOMEN ; SERUM ; case-control study ; REGRESSION ; ASSOCIATIONS ; DETERMINANTS ; development ; LEVEL ; case control studies ; SERUM-LEVELS ; SULFATE ; HORMONES ; DEHYDROEPIANDROSTERONE-SULFATE ; TESTOSTERONE ; prospective ; STEROID-HORMONES ; INCREASED RISK ; odds ratio ; CANCER-RISK ; OVARIAN ; BODY-MASS-INDEX
    Abstract: Few epidemiologic studies have examined the hypothesis that circulating androgens are involved in the development of ovarian cancer. We investigated the association between prediagnostic serum levels of androgens and sex hormone-binding globulin (SHBG) and ovarian cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort. One hundred and ninety-two ovarian cancer cases and 346 matched controls not using exogenous hormones at baseline blood donation were eligible for the study. Serum levels of testosterone, androstenedione, dehydroepiandrosterone sulfate, and SHBG were measured by direct immunoassays. Free testosterone (fT) was calculated according to mass action laws. Multivariate conditional logistic regression was used to estimate odds ratios adjusted for possible confounders. Overall, there was no association between serum concentrations of androgens or SHBG and ovarian cancer risk. In postmenopausal women, fT concentrations were inversely related to risk [highest versus lowest tertile odds ratio 0.45 (0.24-0.86); P-trend = 0-01]. Among women diagnosed before the age of 55 years, there was a negative association with SHBG and a positive association with fT and ovarian cancer risk, although these associations were not statistically significant. The present study suggests that circulating androgens and SHBG levels are not strongly associated with ovarian cancer risk, although levels of fT may be associated with an increased risk among women diagnosed at relatively young age. The heterogeneity of results on the associations of fT with ovarian cancer risk in postmenopausal women deserves further investigation
    Type of Publication: Journal article published
    PubMed ID: 17220328
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  • 8
    Keywords: CANCER ; carcinoma ; INFORMATION ; COHORT ; DEATH ; incidence ; RISK ; SITE ; SITES ; GENE ; INFECTION ; DOWN-REGULATION ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; MOLECULE ; NO ; PROGRESSION ; DIFFERENCE ; PROMOTER ; MUTATION ; smoking ; RATES ; FRANCE ; MUTATIONS ; ADHESION ; case-control studies ; ADHESION MOLECULE ; EPIC ; HELICOBACTER-PYLORI ; nutrition ; SMOKERS ; METHYLATION ; E-cadherin ; ONCOLOGY ; case-control study ; RE ; INCREASE ; gastric cancer ; PROMOTER POLYMORPHISM ; HAPLOTYPE ; prospective ; Helicobacter pylori ; ENGLAND ; block ; GENE POLYMORPHISMS ; GENE POLYMORPHISM ; POSITION ; gastric adenocarcinoma ; CDH1 ; E-CADHERIN GENE
    Abstract: Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. E-Cadherin is an adhesion molecule that is thought to be involved in GC. Germline mutations in the E-Cadherin gene (CDH1) have been identified in hereditary diffuse GC. Also, a promoter polymorphism at position 160 C/A has been suggested to lead to transcriptional down regulation and has been shown to affect GC risk in some studies. However, very little information exists on the GC risk association of other CDH1 polymorphisms and it is unclear whether any associations may be different by GC anatomical sites or histological types. Thus, a case-control study (cases = 245/controls = 950) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort was conducted to assess the GC risk association of eight CDH1 gene polymorphisms. None of the CDH1 polymorphisms or haplotypes analysed were associated with GC risk and no differences of effect were observed by Helicobacter pylori infection status. However, three CDH1 polymorphisms in the same haplotype block, including the CDH1-160C/A, interacted with smoking to increase GC risk in smokers but not in never smokers. These findings should be confirmed in larger independent studies. (c) 2008 Elsevier Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 18342503
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  • 9
    Keywords: CANCER ; Germany ; human ; MODEL ; MODELS ; FOLLOW-UP ; SUPPORT ; DEATH ; RISK ; RISKS ; TIME ; INDEX ; ASSOCIATION ; AGE ; WOMEN ; MEN ; OBESITY ; PROSPECTIVE COHORT ; smoking ; COUNTRIES ; RECRUITMENT ; PREDICTION ; ALCOHOL ; ALCOHOL-CONSUMPTION ; CONSUMPTION ; EPIC ; nutrition ; EUROPE ; RELATIVE RISK ; BODIES ; REGRESSION ; WEIGHT ; PHYSICAL-ACTIVITY ; HEIGHT ; LEVEL ; analysis ; methods ; BODY-MASS INDEX ; ALL-CAUSE MORTALITY ; alcohol consumption ; USA ; prospective ; BMI ; WAIST CIRCUMFERENCE ; TISSUE DISTRIBUTION ; MEDICINE ; NOV ; body mass ; RATIO ; European Prospective Investigation into Cancer ; PREDICTING MORTALITY ; ROC CURVE
    Abstract: BACKGROUND Previous studies have relied predominantly on the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) to assess the association of adiposity with the risk of death, but few have examined whether the distribution of body fat contributes to the prediction of death. METHODS We examined the association of BMI, waist circumference, and waist-to-hip ratio with the risk of death among 359,387 participants from nine countries in the European Prospective Investigation into Cancer and Nutrition (EPIC). We used a Cox regression analysis, with age as the time variable, and stratified the models according to study center and age at recruitment, with further adjustment for educational level, smoking status, alcohol consumption, physical activity, and height. RESULTS During a mean follow-up of 9.7 years, 14,723 participants died. The lowest risks of death related to BMI were observed at a BMI of 25.3 for men and 24.3 for women. After adjustment for BMI, waist circumference and waist-to-hip ratio were strongly associated with the risk of death. Relative risks among men and women in the highest quintile of waist circumference were 2.05 (95% confidence interval [CI], 1.80 to 2.33) and 1.78 (95% CI, 1.56 to 2.04), respectively, and in the highest quintile of waist-to-hip ratio, the relative risks were 1.68 (95% CI, 1.53 to 1.84) and 1.51 (95% CI, 1.37 to 1.66), respectively. BMI remained significantly associated with the risk of death in models that included waist circumference or waist-to-hip ratio (P〈0.001). CONCLUSIONS These data suggest that both general adiposity and abdominal adiposity are associated with the risk of death and support the use of waist circumference or waist-tohip ratio in addition to BMI in assessing the risk of death
    Type of Publication: Journal article published
    PubMed ID: 19005195
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  • 10
    Keywords: CANCER ; Germany ; EXPOSURE ; POPULATION ; RISK ; MECHANISM ; REDUCTION ; RISK-FACTORS ; CARCINOGENESIS ; mechanisms ; ASSOCIATION ; BREAST ; HEALTH ; NUMBER ; AGE ; WOMEN ; risk factors ; REQUIRES ; RISK FACTOR ; ORAL-CONTRACEPTIVES ; EPIC ; nutrition ; ENDOMETRIAL CANCER ; menopause ; ONCOLOGY ; LIFE ; PHYSICAL-ACTIVITY ; ESTROGEN ; PREGNANCY ; BIRTH ; parity ; prospective ; menarche ; VARIABLES ; CANCER-RISK ; OVARIAN ; CORPUS ; oral contraceptive
    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
    Type of Publication: Journal article published
    PubMed ID: 19924816
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