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  • HEALTH  (16)
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  • 1
    Keywords: CANCER ; carcinoma ; Germany ; FOLLOW-UP ; INFORMATION ; COHORT ; EPIDEMIOLOGY ; RISK ; INFECTION ; RISK-FACTORS ; ASSOCIATION ; HEALTH ; REDUCED RISK ; risk factors ; cancer risk ; RECRUITMENT ; DIET ; STOMACH ; adenocarcinoma ; case-control studies ; TOBACCO ; ALCOHOL ; CARDIA ; EPIC ; ESOPHAGUS ; GASTRIC-CANCER ; HELICOBACTER-PYLORI ; nutrition ; STOMACH-CANCER ; case-control study ; ASSOCIATIONS ; DIGESTIVE-TRACT ; gastric cancer ; LEVEL ; case control studies ; INTERVAL ; methods ; PROFILES ; prospective ; EVALUATE ; odds ratio ; RISK-FACTOR ; CANCER-RISK ; Helicobacter pylori ; cardia cancer ; socioeconomic position
    Abstract: Objectives To evaluate the association of socioeconomic position with adenocarcinoma of the oesophagus and stomach. Methods The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort comprises about 520000 participants mostly aged 35-70 years. Information on diet and lifestyle was collected at recruitment. After an average follow-up of 6.5 years, 268 cases with adenocarcinoma of the stomach and 56 of the oesophagus were confirmed. We examined the effect of socioeconomic position on cancer risk by means of educational data and a computed Relative Index of Inequality (RII). In a nested case-control study, adjustment for Helicobacter pylori (H. pylori) infection was performed. Results Higher education was significantly associated with a reduced risk of gastric cancer [vs lowest level of education, hazard ratio (HR): 0.64, 95% Confidence intervals (CI): 0.43-0.981. This effect was more pronounced for cancer of the cardia (HR: 0.42, 95% CI: 0.20-0.89) as compared to non-cardia gastric cancer (HR: 0.66, 95% CI: 0.36-1.22). Additionally, the inverse association of educational level and gastric cancer was stronger for cases with intestinal (extreme categories, HR: 0.13, 95% CI: 0.04-0.44) rather than diffuse histological subtype (extreme categories, HR: 0.71 95% CI: 0.37-1.40). In the nested case-control study, inverse but statistically non-significant associations were found after additional adjustment for H. pylori infection [highest vs lowest level of education: Odds ratio (OR) 0.53, 95% CI: 0.24-1.18]. Educational level was non-significantly, inversely associated with carcinoma of the oesophagus. Conclusion A higher socioeconomic position was associated with a reduced risk of gastric adenocarcinoma, which was strongest for cardia cancer or intestinal histological subtype, suggesting different risk profiles according to educational level. These effects appear to be explained only partially by established risk factors
    Type of Publication: Journal article published
    PubMed ID: 17227779
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  • 2
    Keywords: CANCER ; CELLS ; CELL ; Germany ; MODEL ; MODELS ; FOLLOW-UP ; SYSTEM ; cohort study ; DISEASE ; DISEASES ; EPIDEMIOLOGY ; RISK ; RISK-FACTORS ; ASSOCIATION ; NO ; LYMPHOMA ; HEALTH ; WOMEN ; etiology ; risk factors ; DIETARY ; UNITED-STATES ; ALCOHOL-CONSUMPTION ; CONSUMPTION ; FRUIT ; nutrition ; VEGETABLES ; CALIBRATION ; B-CELL LYMPHOMA ; MULTIPLE-MYELOMA ; NON-HODGKINS-LYMPHOMA ; ONCOLOGY ; DIETARY FACTORS ; ASSOCIATIONS ; IMMUNE-SYSTEM ; non-Hodgkin lymphoma ; INTERVAL ; FRUITS ; methods ; function ; prospective ; prospective study ; RISK-FACTOR ; HODGKIN LYMPHOMA ; B-CELL ; N-NITROSO COMPOUNDS ; DRINKING-WATER NITRATE
    Abstract: Introduction Lymphomas are a heterogeneous group of malignant diseases of cells of the immune system. The best-established risk factors are related to dys-regulation of immune function, and evidence suggests that factors such as dietary or lifestyle habits may be involved in the etiology. Material and methods In the European Prospective Investigation into Cancer and Nutrition (EPIC), 849 lymphoma cases were identified in a median follow-up period of 6.4 years. Fruit and vegetable consumption was estimated from validated dietary questionnaires. Cox proportional hazard models were used to examine the association between fruit and vegetable intake with the risk of lymphomas overall and subentities. Results There was no overall association between total fruit and vegetable consumption and risk of lymphoma [hazard ratio (HR) = 0.95, 95% confidence interval (CI) 0.78-1.15 comparing highest with lowest quartile]. However, the risk of diffuse large B-cell lymphomas (DLBCL) tended to be lower in participants with a high intake of total vegetables (HR = 0.49, 95% CI 0.23-1.02). Conclusion In this large prospective study, an inverse associations between fruit and vegetable consumption and risk of lymphomas overall could not be confirmed. Associations with lymphoma subentities such as DLBCL warrant further investigation
    Type of Publication: Journal article published
    PubMed ID: 17443415
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  • 3
    Keywords: CANCER ; BLOOD ; COHORT ; cohort studies ; cohort study ; POPULATION ; RISK ; MARKER ; BIOMARKERS ; colon ; ASSOCIATION ; NO ; HEALTH ; WOMEN ; colorectal cancer ; MEN ; PROSPECTIVE COHORT ; COLORECTAL-CANCER ; cancer risk ; FRANCE ; COLON-CANCER ; MULTIVARIATE ; UNITED-STATES ; case-control studies ; GLUCOSE ; nutrition ; BETA-CELL FUNCTION ; ONCOLOGY ; case-control study ; REGRESSION ; RE ; INCREASE ; LEVEL ; biomarker ; INSULIN-RESISTANCE ; metabolic syndrome ; USA ; prospective ; cancer research ; CANCER-RISK ; NOV ; HEMOGLOBIN ; TYPE-2 DIABETES-MELLITUS ; European Prospective Investigation into Cancer ; CHRONIC OXIDATIVE STRESS ; GLUCOSE TOXICITY ; RECTAL CANCERS ; SERUM C-PEPTIDE
    Abstract: Although large-scale prospective cohort studies have related hyperglycemia to increased risk of cancer overall, studies specifically on colorectal cancer have been generally small. We investigated the association between prediagnostic levels of glycosylated hemoglobin (HbA1c), a marker for average glucose level in blood, and colorectal cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort. One thousand and twenty-six incident colorectal cancer cases (561 men and 465 women) and 1,026 matched controls were eligible for the study. Multivariate conditional logistic regression was used to estimate odds ratios (ORS) adjusted for possible confounders. Increasing HbA1c percentages were statistically significantly associated with a mild increase in colorectal cancer risk in the whole population [OR, 1.10; 95% confidence interval (CI), 1.01,1.19 for a 10% increase in HbA1c]. In women, increasing HbA1c percentages were associated with a statistically significant increase in colorectal cancer risk (OR, 1.16; 95% CI, 1.01, 1.32 for a 10% increase in HbA1c) and with a borderline statistically significant increase in rectum cancer (OR, 1.22; 95% CI, 0.99,1.50 for a 10% increase in HbA1c). No significant association with cancer risk was observed in men. The results of the current study suggest a mild implication of hyperglycemia in colorectal cancer, which seems more important in women than in men, and more for cancer of the rectum than of the colon. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3108-15)
    Type of Publication: Journal article published
    PubMed ID: 18990751
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  • 4
    Keywords: RECEPTOR ; CANCER ; BLOOD ; POPULATION ; RISK ; GENE ; GENES ; BIOMARKERS ; colon ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; VARIANTS ; ADENOMAS ; HEALTH ; colorectal cancer ; REDUCED RISK ; COLORECTAL-CANCER ; GENOTYPES ; COLON-CANCER ; POPULATIONS ; UNITED-STATES ; case-control studies ; CALCIUM ; nutrition ; RECTAL-CANCER ; SERUM ; case control study ; case-control study ; REGRESSION ; colon cancer ; VARIANT ; interaction ; LEVEL ; biomarker ; EPIDEMIOLOGIC EVIDENCE ; GENOTYPE ; USA ; prospective ; rectal cancer ; cancer research ; colorectal ; vitamin D ; VITAMIN-D ; LOGISTIC-REGRESSION ; D METABOLITES ; vitamin D receptor ; 25-HYDROXYVITAMIN-D ; RECTAL CANCERS ; Genetic ; VITAMIN ; CONFIDENCE ; CRC ; Logistic regression ; D-RECEPTOR ; DIETARY CALCIUM
    Abstract: Increased levels of vitamin D and calcium may play a protective role in colorectal cancer (CRC) risk. It has been suggested that these effects may be mediated by genetic variants of the vitamin D receptor (VDR) and the calcium sensing receptor (CASR). However, current epidemiologic evidence from European populations for a role of these genes in CRC risk is scarce. In addition, it is not clear whether these genes may modulate CRC risk independently or by interaction with blood vitamin D concentration wild-type bb, the BB genotype of the VDR BsmI polymorphism was associated with a reduced risk of CRC [RR, 0.76; 95% confidence interval (CI), 0.59-0.98). The association was observed for colon cancer (RR, 0.69; 95% CI, 0.45-0.95) but not rectal cancer (RR, 0.97; 95% CI, 0.62-1.49). The Fok1 and CASR genotypes were not associated with CRC risk in thisand level of dietary calcium intake. A case-control study was conducted nested within the European Prospective Investigation into Cancer and Nutrition. CRC cases (1,248) were identified and matched to 1,248 control subjects. Genotyping for the VDR (BsmI: rs1544410; Fok1: rs2228570) and CASR (rs1801725) genes was done by Taqman, and serum vitamin D (25OHD) concentrations were measured. Conditional logistic regression was used to estimate the incidence rate ratio (RR). Compared with the study. No interactions were noted for any of the polymorphisms with serum 25OHD concentration or level of dietary calcium. These results confirm a role for the BsmI polymorphism of the VDR gene in CRC risk, independent of serum 25OHD concentration and dietary calcium intake. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2485-91)
    Type of Publication: Journal article published
    PubMed ID: 19706842
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  • 5
    Keywords: CANCER ; carcinoma ; FOLLOW-UP ; INFORMATION ; COHORT ; RISK ; INFECTION ; ASSOCIATION ; PATTERNS ; HEALTH ; MEN ; COUNTRIES ; DIET ; NETHERLANDS ; STOMACH ; adenocarcinoma ; EPIC ; GASTRIC-CANCER ; HELICOBACTER-PYLORI ; nutrition ; physical activity ; ONCOLOGY ; POPULATION-BASED COHORT ; SCALE ; PHYSICAL-ACTIVITY ; METAANALYSIS ; SUBTYPES ; prospective ; CANCERS ; VARIABLES ; Helicobacter pylori ; stomach cancer ; BODY-MASS ; tumours ; gastric adenocarcinoma ; Type ; EURGAST ; REGISTER ; Oesophagus cancer
    Abstract: To analyse the association between types of physical activity (occupational, recreational and household, vigorous and overall) and risk of primary oesophageal (OAC) or gastric adenocarcinoma (GAC). From nine European countries, 420,449 participants were recruited between 1991 and 2000 and followed-up for a mean of 8.8 years to register incident GAC and OAC. Information on physical activity (PA), diet, lifestyle and health-related variables was obtained at baseline. Helicobacter pylori infection status was considered in a subset of 1,211 participants. Analyses were repeated by tumour site (cardia/non-cardia) and histological type (intestinal/diffuse). During the follow-up, 410 GAC and 80 OAC occurred. A lower risk of overall and non-cardia GAC was found for increasing levels of a PA index which combined occupational PA with weekly time spent in sports and cycling. The hazard ratio (HR) of GAC was 0.69, 95% CI: 0.50-0.94, for the comparison between active and inactive participants according to the PA index (HR = 0.44, 95% CI:0.26-0.74, for non-cardia GAC). No effect was found for cardia tumours or histological subtypes of GAC. PA of any kind was not associated with OAC. Overall and distal (non-cardia) gastric tumours were inversely associated with time spent on cycling and sports and a total PA index. No association was found for any type of PA and risk of cardia cancers of the stomach
    Type of Publication: Journal article published
    PubMed ID: 20052611
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  • 6
    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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  • 7
    Keywords: CANCER ; PROSTATE ; FOLLOW-UP ; DISEASE ; RISK ; RISKS ; INDEX ; ASSOCIATION ; NO ; HEALTH ; DESIGN ; PLASMA ; AGE ; MEN ; smoking ; COUNTRIES ; prostate cancer ; PROSTATE-CANCER ; cancer risk ; RECRUITMENT ; DIETARY ; ALCOHOL ; BODY ; European Prospective Investigation into Cancer and Nutrition ; nutrition ; tocopherols ; RELATIVE RISK ; BETA-CAROTENE ; VITAMIN-E ; HETEROGENEITY ; physical activity ; ALPHA-TOCOPHEROL ; carotenoids ; LYCOPENE ; MASS INDEX ; MASSES ; RETINOL ; SERUM ; BODIES ; REGRESSION ; ASSOCIATIONS ; RE ; CARDIOVASCULAR-DISEASE ; SUPPLEMENTATION ; PHYSICAL-ACTIVITY ; LEVEL ; USA ; prospective ; UNIT ; CANCER-RISK ; GAMMA-TOCOPHEROL ; nested case-control study ; micronutrients ; LOGISTIC-REGRESSION ; BODY-MASS ; BODY-MASS-INDEX
    Abstract: Background: Previous studies suggest that high plasma concentrations of carotenoids, retinol, or tocopherols may reduce the risk of prostate cancer. Objective: We aimed to examine the associations between plasma concentrations of 7 carotenoids, retinol, a-tocopherol, and,gamma-tocopherol and prostate cancer risk. Design: A total of 137 001 men in 8 European countries participated. After a mean of 6 y, 966 incident cases of prostate cancer with plasma were available. A total of 1064 control subjects were selected and were matched for study center, age, and date of recruitment. The relative risk of prostate cancer was estimated by conditional logistic regression, which was adjusted for smoking status, alcohol intake, body mass index, marital status, physical activity, and education level. Results: Overall, none of the micronutrients examined were significantly associated with prostate cancer risk. For lycopene and the sum of carotenoids, there was evidence of heterogeneity between the associations with risks of localized and advanced disease. These carotenoids were not associated with the risk of localized disease but were inversely associated with the risk of advanced disease. The risk of advanced disease for men in the highest fifth of plasma concentrations compared with men in the lowest fifth was 0.40 (95% CI: 0. 19, 0.88) for lycopene and 0.35 (95% CI: 0. 17, 0.78) for the sum of carotenoids. Conclusions: We observed no associations between plasma concentrations of carotenoids, retinol, or tocopherols and overall prostate cancer risk. The inverse associations of lycopene and the sum of carotenoids with the risk of advanced disease may involve a protective effect, an association of dietary choice with delayed detection of prostate cancer, reverse causality, or other factors
    Type of Publication: Journal article published
    PubMed ID: 17823432
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  • 8
    Keywords: CANCER ; SURVIVAL ; MODEL ; FOLLOW-UP ; INFORMATION ; COHORT ; DEATH ; DISEASE ; incidence ; MORTALITY ; POPULATION ; RISK ; HEART ; PATIENT ; prognosis ; REDUCTION ; ASSOCIATION ; NO ; TRIAL ; TRIALS ; HEALTH ; AGE ; COUNTRIES ; POPULATIONS ; DIET ; DIETARY ; NETHERLANDS ; MYOCARDIAL-INFARCTION ; ALCOHOL ; IMPROVES ; EPIC ; European Prospective Investigation into Cancer and Nutrition ; nutrition ; FOOD ; HEART-DISEASE ; Mediterranean diet ; HETEROGENEITY ; REGRESSION ; ASSOCIATIONS ; PATTERN ; CORONARY-HEART-DISEASE ; INTERVAL ; elderly ; prospective ; PEOPLE ; UNIT ; COMMUNITY ; myocardial infarction ; coronary heart disease ; DEATHS
    Abstract: Mediterranean diet is associated with lower incidence of coronary heart disease, and two randomised trials indicated that it improves prognosis of coronary patients. These trials, however, relied on a total of 100 deaths and evaluated designer diets in the clinical context. We have evaluated the association of adherence to the modified Mediterranean diet, in which unsaturates were substituted for monounsaturates, with survival among elderly with previous myocardial infarction within the European Prospective Investigation into Cancer and nutrition (EPIC) study. As of December 2003, after a median follow-up of 6.7 years, 2671 EPIC participants from nine countries were 60 years or older and had prevalent myocardial infarction but no stroke or cancer at enrolment, complete information on dietary intakes and important covariates and known survival status. Adherence to the modified Mediterranean diet was assessed through a 10-unit-scale. Mortality ratio in relation to modified Mediterranean diet was estimated through Cox regression controlling for possible confounding. Increased adherence to modified Mediterranean diet by two units was associated with 18% lower overall mortality rate (95% confidence interval 7-27%, fixed effects model). There was no significant heterogeneity by sex, age at enrolment, or country, although the association tended to be less evident among northern Europeans. Associations between food groups contributing to the modified Mediterranean diet and mortality were generally weak. A diet inspired by the Mediterranean pattern that can be easily adopted by Western populations is associated with substantial reduction of total mortality of coronary patients in the community
    Type of Publication: Journal article published
    PubMed ID: 17926134
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  • 9
    Keywords: CANCER ; Germany ; human ; PROSTATE ; FOLLOW-UP ; DISEASE ; RISK ; TIME ; INDEX ; BIOMARKERS ; ASSOCIATION ; HEALTH ; AGE ; MEN ; smoking ; COUNTRIES ; prostate cancer ; PROSTATE-CANCER ; cancer risk ; RECRUITMENT ; UNITED-STATES ; INDIVIDUALS ; ALCOHOL ; ALCOHOL-CONSUMPTION ; CONSUMPTION ; EPIC ; nutrition ; education ; RELATIVE RISK ; BODIES ; ONCOLOGY ; REGRESSION ; PHYSICAL-ACTIVITY ; HEIGHT ; GROWTH-FACTOR-I ; biomarker ; methods ; MASS ; FACTOR (IGF)-I ; alcohol consumption ; USA ; prospective ; HIGH-GRADE ; DIETARY ASSESSMENT METHODS ; BMI ; cancer research ; CANCER-RISK ; PREDICTS ; PREDICT ; NOV ; WEIGHT CHANGE ; body mass ; META-REGRESSION ANALYSIS ; European Prospective Investigation into Cancer ; EPIC-OXFORD PARTICIPANTS ; HEALTH-PROFESSIONALS ; IGF BINDING PROTEIN-3
    Abstract: Background: Body size has been hypothesized to influence the risk of prostate cancer; however, most epidemiologic studies have relied on body mass index (BMI) to assess adiposity, whereas only a few studies have examined whether body fat distribution predicts prostate cancer. Methods: We examined the association of height, BMI, waist and hip circumference, and waist-hip ratio with prostate cancer risk among 129,502 men without cancer at baseline from 8 countries of the European Prospective Investigation into Cancer and Nutrition (EPIC), using Cox regression, with age as time metric, stratifying by study center and age at recruitment, and adjusting for education, smoking status, alcohol consumption, and physical activity. Results: During a mean follow-up of 8.5 years, 2,446 men developed prostate cancer. Waist circumference and waist-hip ratio were positively associated with risk of advanced disease. The relative risk of advanced prostate cancer was 1.06 (95% confidence interval, 1.01-1.1) per 5-cm-higher waist circumference and 1.21 (95% confidence interval, 1.04-1.39) per 0.1-unit-higher waist-hip ratio. When stratified by BMI, waist circumference and waist-hip ratio were positively related to risk of total, advanced, and high-grade prostate cancer among men with lower but not among those with higher BMI (P-interaction for waist with BMI, 0.25, 0.02, and 0.05, respectively; P-interaction for waist-hip ratio with BMI, 0.27, 0.22, and 0.14; respectively). Conclusions: These data suggest that abdominal adiposity may be associated with an increased risk of advanced prostate cancer. This association may be stronger among individuals with lower BMI; however, this finding needs confirmation in future studies. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3252-61)
    Type of Publication: Journal article published
    PubMed ID: 18990768
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  • 10
    Keywords: CANCER ; CELLS ; BLOOD ; MODEL ; MODELS ; PROSTATE ; DIAGNOSIS ; FOLLOW-UP ; SUPPORT ; POPULATION ; RISK ; TIME ; INDEX ; ASSOCIATION ; POLYMORPHISMS ; HEALTH ; AGE ; prostate cancer ; PROSTATE-CANCER ; cancer risk ; UNITED-STATES ; case-control studies ; CALCIUM ; EPIC ; nutrition ; HETEROGENEITY ; SERUM ; case-control study ; REGRESSION ; USA ; prospective ; EUROPEAN COUNTRIES ; CANCER-RISK ; prostatic neoplasms ; vitamin D ; D METABOLITES ; D DEFICIENCY ; 1,25-DIHYDROXYVITAMIN-D ; 25-HYDROXYVITAMIN-D ; 25-hydroxyvitamin D ; SUBSEQUENT DEVELOPMENT ; D-RECEPTOR ; 25-hydroxyvitamin D 2 ; D-BINDING PROTEIN
    Abstract: Results from the majority of studies show little association between circulating concentrations of vitamin D and prostate cancer risk, a finding that has not been demonstrated in a wider European population, however. The authors examined whether vitamin D concentrations were associated with prostate cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (1994-2000). Serum concentrations of 25-hydroxyvitamin D were measured in 652 prostate cancer cases matched to 752 controls from 7 European countries after a median follow-up time of 4.1 years. Conditional logistic regression models were used to calculate odds ratios for prostate cancer risk in relation to serum 25-hydroxyvitamin D after standardizing for month of blood collection and adjusting for covariates. No significant association was found between 25-hydroxyvitamin D and risk of prostate cancer (highest vs. lowest quintile: odds ratio = 1.28, 95% confidence interval: 0.88, 1.88; P for trend = 0.188). Subgroup analyses showed no significant heterogeneity by cancer stage or grade, age at diagnosis, body mass index, time from blood collection to diagnosis, or calcium intake. In summary, the results of this large nested case-control study provide no evidence in support of a protective effect of circulating concentrations of vitamin D on the risk of prostate cancer
    Type of Publication: Journal article published
    PubMed ID: 19359375
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