1,615 research outputs found

    Estimating dose‚ÄĒresponse relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and revised Mendelian randomization analyses

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    Background Randomised trials of vitamin D supplementation for cardiovascular disease and all-cause mortality have generally reported null findings. However, generalisability of results to individuals with low vitamin D status is unclear. We aimed to characterise dose-response relationships between 25-hydroxyvitamin D (25[OH]D) concentrations and risk of coronary heart disease, stroke, and all-cause mortality in observational and Mendelian randomisation frameworks. Methods Observational analyses were undertaken using data from 33 prospective studies comprising 500‚Äą962 individuals with no known history of coronary heart disease or stroke at baseline. Mendelian randomisation analyses were performed in four population-based cohort studies (UK Biobank, EPIC-CVD, and two Copenhagen population-based studies) comprising 386‚Äą406 middle-aged individuals of European ancestries, including 33‚Äą546 people who developed coronary heart disease, 18‚Äą166 people who had a stroke, and 27‚Äą885 people who died. Primary outcomes were coronary heart disease, defined as fatal ischaemic heart disease (International Classification of Diseases 10th revision code I20-I25) or non-fatal myocardial infarction (I21-I23); stroke, defined as any cerebrovascular disease (I60-I69); and all-cause mortality. Findings Observational analyses suggested inverse associations between incident coronary heart disease, stroke, and all-cause mortality outcomes with 25(OH)D concentration at low 25(OH)D concentrations. In population-wide genetic analyses, there were no associations of genetically predicted 25(OH)D with coronary heart disease (odds ratio [OR] per 10 nmol/L higher genetically-predicted 25(OH)D concentration 0¬∑98, 95% CI 0¬∑95‚Äď1¬∑01), stroke (1¬∑01, [0¬∑97‚Äď1¬∑05]), or all-cause mortality (0¬∑99, 0¬∑95‚Äď1¬∑02). Null findings were also observed in genetic analyses for cause-specific mortality outcomes, and in stratified genetic analyses for all outcomes at all observed levels of 25(OH)D concentrations. Interpretation Stratified Mendelian randomisation analyses suggest a lack of causal relationship for 25(OH)D concentrations with both cardiovascular and mortality outcomes for individuals at all levels of 25(OH)D. Our findings suggest that substantial reductions in mortality and cardiovascular morbidity due to long-term low-dose vitamin D supplementation are unlikely even if targeted at individuals with low vitamin D status

    The association between body fatness and mortality among breast cancer survivors: results from a prospective cohort study

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    Evidence linking body fatness to breast cancer (BC) prognosis is limited. While it seems that excess adiposity is associated with poorer BC survival, there is uncertainty over whether weight changes reduce mortality. This study aimed to assess the association between body fatness and weight changes pre- and postdiagnosis and overall mortality and BC-specific mortality among BC survivors. Our study included 13,624 BC survivors from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, with a mean follow-up of 8.6 years after diagnosis. Anthropometric data were obtained at recruitment for all cases and at a second assessment during follow-up for a subsample. We measured general obesity using the body mass index (BMI), whereas waist circumference and A Body Shape Index were used as measures of abdominal obesity. The annual weight change was calculated for cases with two weight assessments. The association with overall mortality and BC-specific mortality were based on a multivariable Cox and Fine and Gray models, respectively. We performed Mendelian randomization (MR) analysis to investigate the potential causal association. Five-unit higher BMI prediagnosis was associated with a 10% (95% confidence interval: 5‚Äď15%) increase in overall mortality and 7% (0‚Äď15%) increase in dying from BC. Women with abdominal obesity demonstrated a 23% (11‚Äď37%) increase in overall mortality, independent of the association of BMI. Results related to weight change postdiagnosis suggested a U-shaped relationship with BC-specific mortality, with higher risk associated with losing weight or gaining‚ÄČ>‚ÄČ2% of the weight annually. MR analyses were consistent with the identified associations. Our results support the detrimental association of excess body fatness on the survival of women with BC. Substantial weight changes postdiagnosis may be associated with poorer survival

    A body shape index (ABSI) is associated inversely with post-menopausal progesterone-receptor-negative breast cancer risk in a large European cohort

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    Abstract Background Associations of body shape with breast cancer risk, independent of body size, are unclear because waist and hip circumferences are correlated strongly positively with body mass index (BMI). Methods We evaluated body shape with the allometric ‚Äúa body shape index‚ÄĚ (ABSI) and hip index (HI), which compare waist and hip circumferences, correspondingly, among individuals with the same weight and height. We examined associations of ABSI, HI, and BMI (per one standard deviation increment) with breast cancer overall, and according to menopausal status at baseline, age at diagnosis, and oestrogen and progesterone receptor status (ER+/-PR+/-) in multivariable Cox proportional hazards models using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Results During a mean follow-up of 14.0 years, 9011 incident breast cancers were diagnosed among 218,276 women. Although there was little evidence for association of ABSI with breast cancer overall (hazard ratio HR‚ÄČ=‚ÄČ0.984; 95% confidence interval: 0.961‚Äď1.007), we found borderline inverse associations for post-menopausal women (HR‚ÄČ=‚ÄČ0.971; 0.942-1.000; n‚ÄČ=‚ÄČ5268 cases) and breast cancers diagnosed at age‚ÄČ‚Č•‚ÄČ55 years (HR‚ÄČ=‚ÄČ0.976; 0.951‚Äď1.002; n‚ÄČ=‚ÄČ7043) and clear inverse associations for ER‚ÄČ+‚ÄČPR- subtypes (HR‚ÄČ=‚ÄČ0.894; 0.822‚Äď0.971; n‚ÄČ=‚ÄČ726) and ER-PR- subtypes (HR‚ÄČ=‚ÄČ0.906; 0.835‚Äď0.983 n‚ÄČ=‚ÄČ759). There were no material associations with HI. BMI was associated strongly positively with breast cancer overall (HR‚ÄČ=‚ÄČ1.074; 1.049‚Äď1.098), for post-menopausal women (HR‚ÄČ=‚ÄČ1.117; 1.085‚Äď1.150), for cancers diagnosed at age‚ÄČ‚Č•‚ÄČ55 years (HR‚ÄČ=‚ÄČ1.104; 1.076‚Äď1.132), and for ER‚ÄČ+‚ÄČPR‚ÄČ+‚ÄČsubtypes (HR‚ÄČ=‚ÄČ1.122; 1.080‚Äď1.165; n‚ÄČ=‚ÄČ3101), but not for PR- subtypes. Conclusions In the EPIC cohort, abdominal obesity evaluated with ABSI was not associated with breast cancer risk overall but was associated inversely with the risk of post-menopausal PR- breast cancer. Our findings require validation in other cohorts and with a larger number of PR- breast cancer cases

    Dietary fatty acids and endometrial cancer risk within the European Prospective Investigation into Cancer and Nutrition

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    BACKGROUND: Diet may impact important risk factors for endometrial cancer such as obesity and inflammation. However, evidence on the role of specific dietary factors is limited. We investigated associations between dietary fatty acids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: This analysis includes 1,886 incident endometrial cancer cases and 297,432 non-cases. All participants were followed up for a mean of 8.8 years. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of endometrial cancer across quintiles of individual fatty acids estimated from various food sources quantified through food frequency questionnaires in the entire EPIC cohort. The false discovery rate (q-values) was computed to control for multiple comparisons. RESULTS: Consumption of n-6 ő≥-linolenic acid was inversely associated with endometrial cancer risk (HR comparing 5th with 1st quintile Q5-Q1=0.77, 95% CI‚ÄČ=‚ÄČ0.64; 0.92, p trend=0.01, q-value‚ÄČ=‚ÄČ0.15). This association was mainly driven by ő≥-linolenic acid derived from plant sources (HR per unit increment=0.94, 95%CI= (0.90;0.98), p‚ÄČ=‚ÄČ0.01) but not from animal sources (HR per unit increment= 1.00, 95%CI = (0.92; 1.07), p‚ÄČ=‚ÄČ0.92). In addition, an inverse association was found between consumption of n-3 őĪ-linolenic acid from vegetable sources and endometrial cancer risk (HR per unit increment= 0.93, 95%CI = (0.87; 0.99), p‚ÄČ=‚ÄČ0.04). No significant association was found between any other fatty acids (individual or grouped) and endometrial cancer risk. CONCLUSION: Our results suggest that higher consumption of ő≥-linolenic acid and őĪ-linoleic acid from plant sources may be associated with lower risk of endometrial cancer

    Risk Factors for Primary Bone Cancer after Childhood Cancer: A PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies Nested Case-Control Study

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    International audiencePURPOSERadiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty regarding the risks of bone tissue radiation doses below 10 Gy and the dose-response relationship for specific types of chemotherapy.METHODSTwelve European countries contributed 228 cases and 228 matched controls to a nested case-control study within a cohort of 69,460 5-year survivors of childhood cancer. Odds ratios (ORs) of developing bone cancer for different levels of cumulative radiation exposure and cumulative doses of specific types of chemotherapy were calculated. Excess ORs were calculated to investigate the shape and extent of any dose-response relationship.RESULTSThe OR associated with bone tissue exposed to 1-4 Gy was 4.8-fold (95% CI, 1.2 to 19.6) and to 5-9 Gy was 9.6-fold (95% CI, 2.4 to 37.4) compared with unexposed bone tissue. The OR increased linearly with increasing dose of radiation (Ptrend <.001) up to 78-fold (95% CI, 9.2 to 669.9) for doses of ‚Č•40 Gy. For cumulative alkylating agent doses of 10,000-19,999 and ‚Č•20,000 mg/m2, the radiation-adjusted ORs were 7.1 (95% CI, 2.2 to 22.8) and 8.3 (95% CI, 2.8 to 24.4), respectively, with independent contributions from each of procarbazine, ifosfamide, and cyclophosphamide. Other cytotoxics were not associated with bone cancer.CONCLUSIONTo our knowledge, we demonstrate - for the first time - that the risk of bone cancer is increased 5- to 10-fold after exposure of bone tissue to cumulative radiation doses of 1-9 Gy. Alkylating agents exceeding 10,000 mg/m2 increase the risk 7- to 8-fold, particularly following procarbazine, ifosfamide, and cyclophosphamide. These substantially elevated risks should be used to develop/update clinical follow-up guidelines and survivorship care plans

    Dietary fatty acids and endometrial cancer risk within the European Prospective Investigation into Cancer and Nutrition

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    Background: Diet may impact important risk factors for endometrial cancer such as obesity and inflammation. However, evidence on the role of specific dietary factors is limited. We investigated associations between dietary fatty acids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: This analysis includes 1,886 incident endometrial cancer cases and 297,432 non-cases. All participants were followed up for a mean of 8.8 years. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of endometrial cancer across quintiles of individual fatty acids estimated from various food sources quantified through food frequency questionnaires in the entire EPIC cohort. The false discovery rate (q-values) was computed to control for multiple comparisons. Results: Consumption of n-6 ő≥-linolenic acid was inversely associated with endometrial cancer risk (HR comparing 5th with 1st quintileQ5‚ąíQ1=0.77, 95% CI = 0.64; 0.92, ptrend=0.01, q-value = 0.15). This association was mainly driven by ő≥-linolenic acid derived from plant sources (HRper unit increment=0.94, 95%CI= (0.90;0.98), p = 0.01) but not from animal sources (HRper unit increment= 1.00, 95%CI = (0.92; 1.07), p = 0.92). In addition, an inverse association was found between consumption of n-3 őĪ-linolenic acid from vegetable sources and endometrial cancer risk (HRper unit increment= 0.93, 95%CI = (0.87; 0.99), p = 0.04). No significant association was found between any other fatty acids (individual or grouped) and endometrial cancer risk. Conclusion: Our results suggest that higher consumption of ő≥-linolenic acid and őĪ-linoleic acid from plant sources may be associated with lower risk of endometrial cancer
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