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Background: Some reproductive factors (such as age at menarche and parity) have been shown to be associated with age at natural menopause, but there has been little quantitative analysis of the association between infertility, miscarriage, stillbirth, and premature (<40 years) or early menopause (40-44 years). In addition, it has been unknown whether the association differs between Asian and non-Asian women, although the age at natural menopause is younger among Asian women., Objective: This study aimed to investigate the association of infertility, miscarriage, and stillbirth with age at natural menopause, and whether the association differed by race (Asian and non-Asian)., Study Design: This was a pooled individual participant data analysis from 9 observational studies contributing to the InterLACE consortium. Naturally postmenopausal women with data on at least 1 of the reproductive factors (ie, infertility, miscarriage, and stillbirth), age at menopause, and confounders (ie, race, education level, age at menarche, body mass index, and smoking status) were included. A multinomial logistic regression model was used to estimate relative risk ratios and 95% confidence intervals for the association of infertility, miscarriage, and stillbirth with premature or early menopause, adjusting for confounders. Between-study difference and within-study correlation were taken into account by including study as a fixed effect and indicating study as a cluster variable. We also examined the association with number of miscarriages (0, 1, 2, ≥3) and stillbirths (0, 1, ≥2), and tested whether the strength of association differed between Asian and non-Asian women., Results: A total of 303,594 postmenopausal women were included. Their median age at natural menopause was 50.0 years (interquartile range, 47.0-52.0). The percentages of women with premature and early menopause were 2.1% and 8.4%, respectively. The relative risk ratios (95% confidence intervals) of premature and early menopause were 2.72 (1.77-4.17) and 1.42 (1.15-1.74) for women with infertility; 1.31 (1.08-1.59) and 1.37 (1.14-1.65) for women with recurrent miscarriages; and 1.54 (1.52-1.56) and 1.39 (1.35-1.43) for women with recurrent stillbirths. Asian women with infertility, recurrent miscarriages (≥3), or recurrent stillbirths (≥2) had higher risk of premature and early menopause compared with non-Asian women with the same reproductive history., Conclusion: Histories of infertility and recurrent miscarriages and stillbirths were associated with higher risk of premature and early menopause, and the associations differed by race, with stronger associations for Asian women with such reproductive history., (Copyright © 2023. Published by Elsevier Inc.)

Background and Aims: Hip fracture affects 1.6 million people globally each year, and increases morbidity and mortality. There is potential for risk reduction through diet modification, but prospective evidence for associations between intake of several foods and nutrients and hip fracture risk is limited. This study aimed to investigate associations between food and nutrient intakes and hip fracture risk in the UK Women's Cohort Study, and to determine the role of body mass index (BMI) as a potential effect modifier., Methods: Dietary, lifestyle, anthropometric, and socio-economic information of UK women, ages 35-69 years, were collected in a survey at recruitment (1995-1998), and included a validated 217-item food frequency questionnaire. Hip fracture cases were identified by linking participant data at recruitment with their Hospital Episode Statistics (HES) up to March 2019. Cox regression models were used to estimate associations between standard portions of food and nutrient intakes and hip fracture risk over a median follow-up time of 22.3 years., Results: Among 26,318 women linked to HES data (556,331 person-years), 822 hip fracture cases were identified. After adjustment for confounders, every additional cup of tea or coffee per day was associated with a 4% lower risk of hip fracture (HR (95% CI): 0.96 (0.92, 1.00)). A 25 g/day increment of dietary protein intake was also associated with a 14% lower risk of hip fracture (0.86 (0.73, 1.00)). In subgroup analyses, BMI modified linear associations between dietary intakes of protein, calcium, total dairy, milk, and tea and hip fracture risk (p interaction  = 0.02, 0.002, 0.003, 0.001, and 0.003, respectively); these foods and nutrients were associated with a reduced risk of hip fracture in underweight but not healthy or overweight participants. In particular, risk of hip fracture in underweight participants (28 cases, 545 participants) was 45% lower for every 25 g/day protein consumed (0.55 (0.38, 0.78))., Conclusions: This is the first prospective cohort study internationally of multiple food and nutrient intakes in relation to hip fracture risk by BMI using linkage to hospital records. Results suggest that the potential roles of some foods and nutrients in hip fracture prevention, particularly protein, tea and coffee in underweight women, merit confirmation., Protocol Registration: Clinicaltrials.gov NCT05081466., Competing Interests: Conflict of interest JEC is Director of Dietary Assessment Ltd, a University of Leeds spin out company supporting measurement of food and nutrient intake using myfood24. The authors declare no other conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Methods for meta-analysis of studies with individual participant data and continuous exposure variables are well described in the statistical literature but are not widely used in clinical and epidemiological research. The purpose of this case study is to make the methods more accessible., Study Design and Setting: A two-stage process is demonstrated. Response curves are estimated separately for each study using fractional polynomials. The study-specific curves are then averaged pointwise over all studies at each value of the exposure. The averaging can be implemented using fixed effects or random effects methods., Results: The methodology is illustrated using samples of real data with continuous outcome and exposure data and several covariates. The sample data set, segments of Stata and R code, and outputs are provided to enable replication of the results., Conclusion: These methods and tools can be adapted to other situations, including for time-to-event or categorical outcomes, different ways of modelling exposure-outcome curves, and different strategies for covariate adjustment., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Worldwide, the prevalence of dementia is increasing and diet as a modifiable factor could play a role. Meat consumption has been cross-sectionally associated with dementia risk, but specific amounts and types related to risk of incident dementia remain poorly understood., Objective: We aimed to investigate associations between meat consumption and risk of incident dementia in the UK Biobank cohort., Methods: Meat consumption was estimated using a short dietary questionnaire at recruitment and repeated 24-h dietary assessments. Incident all-cause dementia comprising Alzheimer disease (AD) and vascular dementia (VD) was identified by electronic linkages to hospital and mortality records. HRs for each meat type in relation to each dementia outcome were estimated in Cox proportional hazard models. Interactions between meat consumption and the apolipoprotein E (APOE) ε4 allele were additionally explored., Results: Among 493,888 participants included, 2896 incident cases of all-cause dementia, 1006 cases of AD, and 490 cases of VD were identified, with mean ± SD follow-up of 8 ± 1.1 y. Each additional 25 g/day intake of processed meat was associated with increased risks of incident all-cause dementia (HR: 1.44; 95% CI: 1.24, 1.67; P-trend < 0.001) and AD (HR: 1.52; 95% CI: 1.18, 1.96; P-trend = 0.001). In contrast, a 50-g/d increment in unprocessed red meat intake was associated with reduced risks of all-cause dementia (HR: 0.81; 95% CI: 0.69, 0.95; P-trend = 0.011) and AD (HR: 0.70; 95% CI: 0.53, 0.92; P-trend = 0.009). The linear trend was not significant for unprocessed poultry and total meat. Regarding incident VD, there were no statistically significant linear trends identified, although for processed meat, higher consumption categories were associated with increased risks. The APOE ε4 allele increased dementia risk by 3 to 6 times but did not modify the associations with diet significantly., Conclusion: These findings highlight processed-meat consumption as a potential risk factor for incident dementia, independent of the APOE ε4 allele., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Long-term childhood and young adult cancer survivors are at increased risk of the late effects of multiple chronic conditions. In this study we estimate the cumulative burden of subsequent malignant neoplasms (SMN), cardiovascular and respiratory hospitalisations in long-term survivors of childhood and young adult cancers and associated treatment risks., Methods: Five-year survivors of cancer diagnosed aged 0-29 years between 1992-2009 in Yorkshire, UK were included. The cumulative count of all hospital admissions (including readmissions) for cardiovascular and respiratory conditions and all SMNs diagnosed up to 2015 was calculated, with death as a competing risk. Associations between treatment exposures and cumulative burden were investigated using multiple-failure time survival models., Results: A total of 3464 5-year survivors were included with a median follow-up of 8.2 years (IQR 4-13 years). Ten-years post diagnosis, the cumulative incidence for a respiratory admission was 6.0 % (95 %CI 5.2-6.9), a cardiovascular admission was 2.0 % (95 %CI 1.5-2.5), and SMN was 1.0 % (95 % CI 0.7-1.4) with an average of 13 events per 100 survivors observed (95 %CI 11-15). The risk of experiencing multiple events was higher for those treated with chemotherapy drugs with known lung toxicity (HR = 1.35, 95 %CI 1.09-1.68)., Discussion: Survivors of childhood and young adult cancer experience a high burden of morbidity due to respiratory, cardiovascular diseases and SMNs up to 20-years post-diagnosis. Statistical methods that capture multiple morbidities and recurrent events are important when quantifying the burden of late effects in young cancer survivors., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Previous meta-analyses of randomized controlled trials (RCTs) of vitamin D supplementation and total cancer incidence and mortality found inconsistent results, and most included trials administered generally low doses of vitamin D (≤1100 IU/day). We updated the meta-analysis by incorporating recent RCTs that have tested higher doses of vitamin D supplements., Materials and Methods: PubMed and Embase were searched from the inception to November 2018. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a random-effects model., Results: For total cancer incidence, 10 trials were included [6537 cases; 3-10 years of follow-up; 54-135 nmol/l of attained levels of circulating 25(OH) vitamin D [25(OH)D] in the intervention group]. The summary RR was 0.98 (95% CI, 0.93-1.03; P = 0.42; I2 = 0%). The results remained null across subgroups tested, including even when attained 25(OH)D levels exceeded 100 nmol/l (RR, 0.95; 95% CI, 0.83-1.09; P = 0.48; I2 = 26%). For total cancer mortality, five trials were included [1591 deaths; 3-10 years of follow-up; 54-135 nmol/l of attained levels of circulating 25(OH)D in the intervention group]. The summary RR was 0.87 (95% CI, 0.79-0.96; P = 0.005; I2 = 0%), which was largely attributable to interventions with daily dosing (as opposed to infrequent bolus dosing). No statistically significant heterogeneity was observed by attained levels of circulating 25(OH)D (Pheterogeneity = 0.83), with RR being 0.88 (95% CI, 0.78-0.98; P = 0.02; I2 = 0%) for ≤100 nmol/l and 0.85 (95% CI, 0.70-1.03; P = 0.11; I2 = 0%) for >100 nmol/l., Conclusions: In an updated meta-analysis of RCTs, vitamin D supplementation significantly reduced total cancer mortality but did not reduce total cancer incidence., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: To summarise the evidence on the associations between body mass index (BMI) and BMI in early adulthood, height, waist circumference (WC) and waist-to-hip ratio (WHR), and risk of lympho-haematopoietic cancers., Method: We conducted a meta-analysis of prospective studies and identified relevant studies published up to December 2017 by searching PubMed. A random-effects model was used to calculate dose-response summary relative risks (RRs)., Results: Our findings showed BMI, and BMI in early adulthood (aged 18-21 years) is associated with the risk of Hodgkin's and non-Hodgkin's lymphoma (HL and NHL), diffuse large beta-cell lymphoma (DLBCL), Leukaemia including acute and chronic myeloid lymphoma (AML and CML), and chronic lymphocytic leukaemia (CLL) and multiple myeloma (MM). The summary RR per 5 kg/m2 increase in BMI were 1.12 [95% confidence interval (CI): 1.05-1.20] for HL, 1.05 (95% CI: 1.03-1.08) for NHL, 1.11 (95% CI: 1.05-1.16) for DLBCL, 1.06 (95% CI: 1.03-1.09) for ML, 1.09 (95% CI: 1.03-1.15) for leukaemia, 1.13 (95% CI: 1.04-1.24) for AML, 1.13 (95% CI: 1.05-1.22) for CML and 1.04 (95% CI: 1.00-1.09) for CLL, and were1.12 (95% CI: 1.05-1.19) for NHL, 1.22 (95% CI: 1.09-1.37) for DLBCL, and 1.19 (95% CI: 1.03-1.38) for FL for BMI in early adulthood analysis. Results on mortality showed a 15%, 16% and 17% increased risk of NHL, MM and leukaemia, respectively. Greater height increased the risk of NHL by 7%, DLBCL by 10%, FL by 9%, MM by 5% and Leukaemia by 7%. WHR was associated with increased risk of DLBCL by 12%. No association was found between higher WC and risk of MM., Conclusion: Our results revealed that general adiposity in adulthood and early adulthood, and greater height may increase the risk of almost all types of lympho-haematopoietic cancers and this adds to a growing body of evidence linking body fatness to several types of cancers., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: High dietary intake or blood concentrations (as biomarkers of dietary intake) of vitamin C, carotenoids, and vitamin E have been associated with reduced risk of cardiovascular disease, cancer, and mortality, but these associations have not been systematically assessed., Objective: We conducted a systematic review and meta-analysis of prospective studies of dietary intake and blood concentrations of vitamin C, carotenoids, and vitamin E in relation to these outcomes., Design: We searched PubMed and Embase up to 14 February 2018. Summary RRs and 95% CIs were calculated with the use of random-effects models., Results: Sixty-nine prospective studies (99 publications) were included. The summary RR per 100-mg/d increment of dietary vitamin C intake was 0.88 (95% CI: 0.79, 0.98, I2 = 65%, n = 11) for coronary heart disease, 0.92 (95% CI: 0.87, 0.98, I2 = 68%, n = 12) for stroke, 0.89 (95% CI: 0.85, 0.94, I2 = 27%, n = 10) for cardiovascular disease, 0.93 (95% CI: 0.87, 0.99, I2 = 46%, n = 8) for total cancer, and 0.89 (95% CI: 0.85, 0.94, I2 = 80%, n = 14) for all-cause mortality. Corresponding RRs per 50-μmol/L increase in blood concentrations of vitamin C were 0.74 (95% CI: 0.65, 0.83, I2 = 0%, n = 4), 0.70 (95% CI: 0.61, 0.81, I2 = 0%, n = 4), 0.76 (95% CI: 0.65, 0.87, I2 = 56%, n = 6), 0.74 (95% CI: 0.66, 0.82, I2 = 0%, n = 5), and 0.72 (95% CI: 0.66, 0.79, I2 = 0%, n = 8). Dietary intake and/or blood concentrations of carotenoids (total, β-carotene, α-carotene, β-cryptoxanthin, lycopene) and α-tocopherol, but not dietary vitamin E, were similarly inversely associated with coronary heart disease, stroke, cardiovascular disease, cancer, and/or all-cause mortality., Conclusions: Higher dietary intake and/or blood concentrations of vitamin C, carotenoids, and α-tocopherol (as markers of fruit and vegetable intake) were associated with reduced risk of cardiovascular disease, total cancer, and all-cause mortality. These results support recommendations to increase fruit and vegetable intake, but not antioxidant supplement use, for chronic disease prevention.

Background: In the 2007 World Cancer Research Fund/American Institute for Cancer Research Second Expert Report, the expert panel judged that there was strong evidence that alcoholic drinks and body fatness increased esophageal cancer risk, whereas fruits and vegetables probably decreased its risk. The judgments were mainly based on case-control studies. As part of the Continuous Update Project, we updated the scientific evidence accumulated from cohort studies in this topic., Methods: We updated the Continuous Update Project database up to 10 January 2017 by searching in PubMed and conducted dose-response meta-analyses to estimate summary relative risks (RRs) and 95% confidence intervals (CIs) using random effects model., Results: A total of 57 cohort studies were included in 13 meta-analyses. Esophageal adenocarcinoma risk was inversely related to vegetable intake (RR per 100 g/day: 0.89, 95% CI: 0.80-0.99, n = 3) and directly associated with body mass index (RR per 5 kg/m2: 1.47, 95% CI: 1.34-1.61, n = 9). For esophageal squamous cell carcinoma, inverse associations were observed with fruit intake (RR for 100 g/day increment: 0.84, 95% CI: 0.75-0.94, n = 3) and body mass index (RR for 5 kg/m2 increment: 0.64, 95% CI: 0.56-0.73, n = 8), and direct associations with intakes of processed meats (RR for 50 g/day increment: 1.59, 95% CI: 1.11-2.28, n = 3), processed and red meats (RR for 100 g/day increment: 1.37, 95% CI: 1.04-1.82, n = 3) and alcohol (RR for 10 g/day increment: 1.25, 95% CI: 1.12-1.41, n = 6)., Conclusions: Evidence from cohort studies suggested a protective role of vegetables and body weight control in esophageal adenocarcinomas development. For squamous cell carcinomas, higher intakes of red and processed meats and alcohol may increase the risk, whereas fruits intake may play a protective role., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)

Nutritional epidemiology is an inherently complex and multifaceted research area. Dietary intake is a complex exposure and is challenging to describe and assess, and links between diet, health, and disease are difficult to ascertain. Consequently, adequate reporting is necessary to facilitate comprehension, interpretation, and generalizability of results and conclusions. The STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement is an international and collaborative initiative aiming to enhance the quality of reporting of observational studies. We previously presented a checklist of 24 reporting recommendations for the field of nutritional epidemiology, called "the STROBE-nut." The STROBE-nut is an extension of the general STROBE statement, intended to complement the STROBE recommendations to improve and standardize the reporting in nutritional epidemiology. The aim of the present article is to explain the rationale for, and elaborate on, the STROBE-nut recommendations to enhance the clarity and to facilitate the understanding of the guidelines. Examples from the published literature are used as illustrations, and references are provided for further reading., Competing Interests: Author disclosures: AH, CB, EF, C Larsson, ES, AÅ, C Lachat, DH, PK, GB, WDK, JVC, JEC, DCG, NS, MC, ME, IH, and EW, no conflicts of interest. JEC is Principal Investigator and DCG is Co-Investigator on a grant from the Medical Research Council (MR/L02019X/1) that is looking at ways to improve the quality of dietary assessment. MC acted as coordinator of the STROBE collaboration.

Background: Colorectal adenomas are known as precursors for the majority of colorectal carcinomas. While weight gain during adulthood has been identified as a risk factor for colorectal cancer, the association is less clear for colorectal adenomas. We conducted a systematic review and meta-analysis to quantify the evidence on this association., Methods: We searched Medline up to September 2016 to identify observational (prospective, cross-sectional and retrospective) studies on weight gain during adulthood and colorectal adenoma occurrence and recurrence. We conducted meta-analysis on high weight gain versus stable weight, linear and non-linear dose-response meta-analyses to analyze the association. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using a random effects model., Results: For colorectal adenoma occurrence, the summary OR was 1.39 (95% CI: 1.17-1.65; I2: 43%, N = 9 studies, cases = 5507) comparing high (midpoint: 17.4 kg) versus stable weight gain during adulthood and with each 5 kg weight gain the odds increased by 7% (2%-11%; I2: 65%, N = 7 studies). Although there was indication of non-linearity (Pnon-linearity < 0.001) there was an increased odds of colorectal adenoma throughout the whole range of weight gain. Three studies were identified investigating the association between weight gain and colorectal adenoma recurrence and data were limited to draw firm conclusions., Conclusions: Even a small amount of adult weight gain was related to a higher odds of colorectal adenoma occurrence. Our findings add to the benefits of weight control in adulthood regarding colorectal adenoma occurrence, which might be relevant for early prevention of colorectal cancer., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: High blood pressure is a strong risk factor for cardiovascular disease. Objective: The aim of this study was to determine the associations of dietary glycemic index (GI) and glycemic load (GL) with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in healthy individuals. Design: A systematic review and meta-analysis of randomized controlled trials (RCTs) was carried out. Databases were searched for eligible RCTs in 2 phases. MEDLINE, Embase, CAB Abstracts, BIOSIS, ISI Web of Science, and the Cochrane Library were searched from January 1990 to December 2009. An updated search was undertaken with the use of MEDLINE and Embase from January 2010 to September 2016. Trials were included if they reported author-defined high- and low-GI or -GL diets and blood pressure, were of ≥6 wk duration, and comprised healthy participants without chronic conditions. Data were extracted and analyzed with the use of Stata statistical software. Pooled estimates and 95% CIs were calculated with the use of weighted mean differences and random-effects models. Results: Data were extracted from 14 trials comprising 1097 participants. Thirteen trials provided information on differences in GI between control and intervention arms. A median reduction in GI of 10 units reduced the overall pooled estimates for SBP and DBP by 1.1 mm Hg (95% CI: -0.3, 2.5 mm Hg; P = 0.11) and 1.3 mm Hg (95% CI: 0.2 mm Hg, 2.3; P = 0.02), respectively. Nine trials reported information on differences in GL between arms. A median reduction in GL of 28 units reduced the overall pooled estimates for SBP and DBP by 2.0 mm Hg (95% CI: 0.2, 3.8 mm Hg; P = 0.03) and 1.4 mm Hg (95% CI: 0.1, 2.6 mm Hg; P = 0.03), respectively. Conclusions: This review of healthy individuals indicated that a lower glycemic diet may lead to important reductions in blood pressure. However, many of the trials included in the analysis reported important sources of bias. This trial was registered at PROSPERO as CRD42016049026., (© 2017 American Society for Nutrition.)

Background: Greater body mass index (BMI) has been convincingly related to increased endometrial cancer risk, however, whether adiposity earlier in life or abdominal fatness is an independent risk factor and whether weight gain or greater height increases the risk is not clear., Methods: As part of the Continuous Update Project of the World Cancer Research Fund International, we conducted a systematic review and meta-analysis of prospective studies of the association between anthropometric measures and endometrial cancer risk and searched PubMed and several other databases up to February 2015. Summary relative risks (RRs) were calculated using a random-effects model., Results: Thirty prospective studies of BMI and endometrial cancer risk with 22 320 cases among 6 445 402 participants were included. The summary RR for a 5-unit increment was 1.54 [95% confidence interval (CI) 1.47-1.61, I(2) = 81%]. Although the test for non-linearity was significant, Pnon-linearity < 0.0001, and the curve was steeper within the overweight and obese BMI ranges, there was evidence of increased risk even within the high normal BMI range. The summary RR was 1.45 (95% CI 1.28-1.64, I(2) = 76%) per 5 BMI units for BMI in young adulthood, 1.18 (95% CI 1.14-1.23, I(2) = 67%) per 5 kg increase of weight, and 1.16 (95% CI 1.12-1.20, I(2) = 51%) per 5 kg of weight gained between young adulthood and study baseline, 1.27 (95% CI 1.17-1.39, I(2) = 71%) per 10 cm increase in waist circumference, 1.21 (95% CI 1.13-1.29, I(2) = 0%) per 0.1-unit increment in waist-to-hip ratio and 1.30 (95% CI 1.19-1.41, I(2) = 0%) per 10-cm increase in hips circumference. The summary RR was 1.15 (95% CI 1.09-1.22, I(2) = 61%) for a 10-cm increase in height., Conclusions: All measures of adiposity were associated with increased risk of endometrial cancer, and in addition increasing height was associated with increased risk., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Obesity-related hormonal and metabolic perturbations implicated in colorectal carcinogenesis are mainly driven by visceral adipose tissue (VAT) rather than subcutaneous adipose tissue (SAT). Yet, most epidemiologic studies have examined the relationship between excess adiposity and colorectal neoplasia using body mass index (BMI) and waist circumference (WC). Due to the inability of BMI and WC to distinguish VAT from SAT, they are likely to have underestimated the true association., Patients and Methods: We conducted a dose-response meta-analysis to summarize the relationships between VAT and colorectal adenomas and to examine the value of VAT as an independent risk factor beyond BMI, WC, and SAT. PubMed and Embase were searched through September 2014 to identify relevant observational studies. The summary odds ratio (OR) 95% confidence interval (CI) were estimated using a random-effects model., Results: In linear dose-response meta-analysis, the summary OR for each 25 cm(2) increase in VAT area was 1.13 (95% CI 1.05-1.21; I(2) = 62%; 6 studies; 2776 cases; range of VAT area = 30-228 cm(2)). The dose-response curve suggested no evidence of nonlinearity (Pnon-linearity = 0.37). In meta-analysis comparing the highest versus lowest category of VAT based on 12 studies, a positive association between VAT and adenomas remained statistically significant even after adjustment for BMI, WC, and SAT. In contrast, adjustment for VAT substantially attenuated associations of BMI, WC, and SAT with adenomas. Across the studies, VAT was more strongly associated with advanced adenomas than nonadvanced adenomas., Conclusions: VAT may be the underlying mediator of the observed associations of BMI and WC with adenomas, increasing adenoma risk continuously over a wide range of VAT area. Considering that the joint use of BMI and WC better captures VAT than the use of either one, clinicians are recommended to use both BMI and WC to identify those at high risk for colorectal neoplasia., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Dairy product and calcium intakes have been associated with increased prostate cancer risk, but whether specific dairy products or calcium sources are associated with risk is unclear., Objective: In the Continuous Update Project, we conducted a meta-analysis of prospective studies on intakes of dairy products and calcium and prostate cancer risk., Design: PubMed and several other databases were searched up to April 2013. Summary RRs were estimated by using a random-effects model., Results: Thirty-two studies were included. Intakes of total dairy products [summary RR: 1.07 (95% CI: 1.02, 1.12; n = 15) per 400 g/d], total milk [summary RR: 1.03 (95% CI: 1.00, 1.07; n = 14) per 200 g/d], low-fat milk [summary RR: 1.06 (95% CI: 1.01, 1.11; n = 6) per 200 g/d], cheese [summary RR: 1.09 (95% CI: 1.02, 1.18; n = 11) per 50 g/d], and dietary calcium [summary RR: 1.05 (95% CI: 1.02, 1.09; n = 15) per 400 mg/d] were associated with increased total prostate cancer risk. Total calcium and dairy calcium intakes, but not nondairy calcium or supplemental calcium intakes, were also positively associated with total prostate cancer risk. Supplemental calcium was associated with increased risk of fatal prostate cancer., Conclusions: High intakes of dairy products, milk, low-fat milk, cheese, and total, dietary, and dairy calcium, but not supplemental or nondairy calcium, may increase total prostate cancer risk. The diverging results for types of dairy products and sources of calcium suggest that other components of dairy rather than fat and calcium may increase prostate cancer risk. Any additional studies should report detailed results for subtypes of prostate cancer., (© 2015 American Society for Nutrition.)

Background: Positive association between obesity and survival after breast cancer was demonstrated in previous meta-analyses of published data, but only the results for the comparison of obese versus non-obese was summarised., Methods: We systematically searched in MEDLINE and EMBASE for follow-up studies of breast cancer survivors with body mass index (BMI) before and after diagnosis, and total and cause-specific mortality until June 2013, as part of the World Cancer Research Fund Continuous Update Project. Random-effects meta-analyses were conducted to explore the magnitude and the shape of the associations., Results: Eighty-two studies, including 213 075 breast cancer survivors with 41 477 deaths (23 182 from breast cancer) were identified. For BMI before diagnosis, compared with normal weight women, the summary relative risks (RRs) of total mortality were 1.41 [95% confidence interval (CI) 1.29-1.53] for obese (BMI >30.0), 1.07 (95 CI 1.02-1.12) for overweight (BMI 25.0-<30.0) and 1.10 (95% CI 0.92-1.31) for underweight (BMI <18.5) women. For obese women, the summary RRs were 1.75 (95% CI 1.26-2.41) for pre-menopausal and 1.34 (95% CI 1.18-1.53) for post-menopausal breast cancer. For each 5 kg/m(2) increment of BMI before, <12 months after, and ≥12 months after diagnosis, increased risks of 17%, 11%, and 8% for total mortality, and 18%, 14%, and 29% for breast cancer mortality were observed, respectively., Conclusions: Obesity is associated with poorer overall and breast cancer survival in pre- and post-menopausal breast cancer, regardless of when BMI is ascertained. Being overweight is also related to a higher risk of mortality. Randomised clinical trials are needed to test interventions for weight loss and maintenance on survival in women with breast cancer., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)

Background: Mortality rates after acute myocardial infarction (AMI) have declined, but there is uncertainty regarding the extent of improvements in early mortality in the elderly., Methods: Mixed-effects regression analysis of 30-day mortality using data from 478,242 patients with AMI at 215 hospitals in England and Wales stratified by STEMI/NSTEMI, sex, and age group. A hospital opportunity-based composite score (OBCS) for aspirin, ACE-inhibitor, statin, β blocker, and referral for cardiac rehabilitation was used as measure of quality of hospital care., Results: 30-day mortality rates (95% CI) fell from 10.7% (10.6 to 10.9%) in 2004/5 to 8.4% (8.3 to 8.6%) in 2008/9. The median (IQR) hospital OBCSs increased over time, 2004/5: 87.3 (7.2), 2006/7: 88.9 (6.3), 2008/9: 90.3 (6.1), P<0.001, and were similar between age groups (18 to <65 years, 65 to 79 years, and ≥ 80 years) for STEMI: 89.4 (6.5) vs. 89.4 (6.6), vs. 89.2 (6.5) and NSTEMI: 88.6 (7.3) vs. 88.8 (7.0) vs. 88.9 (7.0), respectively For males, all age groups except patients <65 years demonstrated a significant decrease in adjusted mortality. For females, only patients ≥ 80 years demonstrated a significant reduction in adjusted mortality. A 1% increase in hospital OBCS was associated with a 1% decrease in 30-day mortality (95% CI: 0.99 to 0.99, P<0.001)., Conclusion: In England and Wales, for patients with AMI there are age and sex-dependent differences in improvements in 30-day mortality. Whereas young males with AMI have reached an acceptable performance plateau, all other groups are either improving or, more importantly, are yet to demonstrate this., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: To our knowledge, no reviews have assessed the impact of a range of multi- and single-component school-based programs on daily fruit and vegetable intake by using a meta-analysis., Objective: The aim of this study was to quantify the impact of school-based interventions on fruit and vegetable intake in children aged 5-12 y., Design: A systematic literature review was carried out to identify randomized and nonrandomized controlled trials that were based in primary schools and designed to increase portions of daily fruit and vegetable intake. MEDLINE, Cochrane libraries, EMBASE, PsycINFO, and Educational Information Centre were searched from 1985 to 2009. Data were extracted, and mean effect sizes were calculated by using random effects models., Results: A total of 27 school-based programs involving 26,361 children were identified that met the inclusion criteria and assessed the daily weight of fruit and vegetable intake combined, fruit intake only, or vegetable intake only, and 21 studies were used in meta-analyses. The results of the meta-analyses indicated an improvement of 0.25 portions (95% CI: 0.06, 0.43 portions) of fruit and vegetable daily intake if fruit juice was excluded and an improvement of 0.32 portions (95% CI: 0.14, 0.50 portions) if fruit juice was included. Improvement was mainly due to increases in fruit consumption but not in vegetable consumption. The results of the meta-analyses for fruit (excluding juice) and vegetables separately indicated an improvement of 0.24 portions (95% CI: 0.05, 0.43 portions) and 0.07 portions (95% CI: -0.03, 0.16 portions), respectively., Conclusions: School-based interventions moderately improve fruit intake but have minimal impact on vegetable intake. Additional studies are needed to address the barriers for success in changing dietary behavior, particularly in relation to vegetables.

Background: Dietary carbohydrates, glycemic load and glycemic index have been hypothesized to influence pancreatic cancer risk, but epidemiological studies have been inconsistent. We conducted a systematic review and meta-analysis of prospective studies to clarify these results., Methods: PubMed and several other databases were searched for prospective studies of intake of carbohydrates, glycemic index and glycemic load and pancreatic cancer up to September 2011. Summary relative risks were estimated using a random effects model., Results: Ten cohort studies (13 publications) were included in the meta-analysis. The summary relative risk (RR) per 10 glycemic index units was 1.02 [95% confidence interval (CI): 0.93-1.12, I(2) = 0%], per 50 glycemic load units was 1.03 (95% CI: 0.93-1.14, I(2) = 10%), per 100 g/day of total carbohydrates was 0.97 (95% CI: 0.81-1.16, I(2) = 35%), and per 25 g/day of sucrose intake was 1.05 (95% CI: 0.85-1.23, I(2) = 53%). A positive association was observed with fructose intake, summary RR = 1.22 (95% CI: 1.08-1.37, I(2) = 0%) per 25 g/day., Conclusions: This meta-analysis does not support an association between diets high in glycemic index, glycemic load, total carbohydrates or sucrose and pancreatic cancer risk. The finding of an increased risk with fructose intake warrants further investigation in studies with better adjustment for confounding and in non-American populations.

Background: Measurement errors in the dietary assessment of fruit and vegetable intake may attenuate associations with breast cancer risk and might explain the weak associations observed in epidemiologic studies. Carotenoid concentrations in blood are biomarkers of fruit and vegetable intake; however, no systematic assessment has compared dietary intake with blood concentrations of carotenoids and breast cancer risk., Objective: We conducted a systematic review and meta-analysis of prospective studies of dietary intake and blood concentrations of carotenoids and breast cancer risk., Design: We searched PubMed and several other databases for relevant studies up to 31 August 2011. Random-effects models were used to estimate summary estimates., Results: Of the 6 dietary carotenoids assessed, only intake of β-carotene was significantly associated with a reduced breast cancer risk (summary RR: 0.95; 95% CI: 0.91, 0.99; I(2): 0%) per 5000 μg/d (n = 10). In contrast, the summary RR for blood concentrations of carotenoids was 0.78 (95% CI: 0.61, 0.99; I(2): 53%) per 100 μg total carotenoids/dL (n = 7), 0.74 (95% CI: 0.57, 0.97; I(2): 43%) per 50 μg β-carotene/dL (n = 13), 0.82 (95% CI: 0.73, 0.92, I(2): 3%) per 10 μg α-carotene/dL (n = 12), and 0.68 (95% CI: 0.52, 0.89; I(2): 0%) per 25 μg lutein/dL (n = 6)., Conclusions: Blood concentrations of carotenoids are more strongly associated with reduced breast cancer risk than are carotenoids assessed by dietary questionnaires. Our results suggest that the use of certain biomarkers may clarify inconsistent and weak results between dietary intake and breast cancer risk.

Background: Prostate cancer is a growing public health problem. Several human studies have shown a potentially protective effect of selenium, but the conclusions from published reports are inconsistent., Objective: The objective was to examine the evidence for relations between selenium intake, selenium status, and prostate cancer risk., Design: This was a systematic review and meta-analysis of randomized controlled trials, case-control studies, and prospective cohort studies. The World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project database was searched up to September 2010. The studies included reported measurements of selenium intake or status (plasma, serum, or toenail selenium), assessments of prostate cancer cases (number of events), and the RR in the adult population. Meta-analyses were performed, and study quality, heterogeneity, and small study effects were assessed. Dose-response meta-analyses were used, with restricted cubic splines and fractional polynomials for nonlinear trends, to investigate the association between selenium status and prostate cancer risk., Results: Twelve studies with a total of 13,254 participants and 5007 cases of prostate cancer were included. The relation between plasma/serum selenium and prostate cancer in a nonlinear dose-response meta-analysis showed that the risk decreased with increasing plasma/serum selenium up to 170 ng/mL. Three high-quality studies included in the meta-analysis of toenail selenium and cancer risk indicated a reduction in prostate cancer risk (estimated RR: 0.29; 95% CI: 0.14, 0.61) with a toenail selenium concentration between 0.85 and 0.94 μg/g., Conclusion: The relation between selenium status and decreased prostate cancer risk was examined over a relatively narrow range of selenium status; further studies in low-selenium populations are required.

Background: Evidence from case-control studies suggest that dietary fiber may be inversely related to breast cancer risk, but it is unclear if this is supported by prospective data. We conducted a systematic review and meta-analysis of the evidence from prospective studies., Methods: PubMed was searched for prospective studies of fiber intake and breast cancer risk until 31st August 2011. Random effects models were used to estimate summary relative risks (RRs)., Results: Sixteen prospective studies were included. The summary RR for the highest versus the lowest intake was 0.93 [95% confidence interval (CI) 0.89-0.98, I(2) = 0%] for dietary fiber, 0.95 (95% CI 0.86-1.06, I(2) = 4%) for fruit fiber, 0.99 (95% CI 0.92-1.07, I(2) = 1%) for vegetable fiber, 0.96 (95% CI 0.90-1.02, I(2) = 5%) for cereal fiber, 0.91 (95% CI 0.84-0.99, I(2) = 7%) for soluble fiber and 0.95 (95% CI 0.89-1.02, I(2) = 0%) for insoluble fiber. The summary RR per 10 g/day of dietary fiber was 0.95 (95% CI 0.91-0.98, I(2) = 0%, P(heterogeneity) = 0.82). In stratified analyses, the inverse association was only observed among studies with a large range (≥13 g/day) or high level of intake (≥25 g/day)., Conclusion: In this meta-analysis of prospective studies, there was an inverse association between dietary fiber intake and breast cancer risk.

Background: Questions remain about the shape of the dose-response relationship between body mass index (BMI) and pancreatic cancer risk, possible confounding by smoking, and differences by gender or geographic location. Whether abdominal obesity increases risk is unclear., Methods: We conducted a systematic review and meta-analysis of prospective studies of the association between BMI, abdominal fatness and pancreatic cancer risk and searched PubMed and several other databases up to January 2011. Summary relative risks (RRs) were calculated using a random-effects model., Results: Twenty-three prospective studies of BMI and pancreatic cancer risk with 9504 cases were included. The summary RR for a 5-unit increment was 1.10 [95% confidence interval (CI) 1.07-1.14, I(2) = 19%] and results were similar when stratified by gender and geographic location. There was evidence of a non-linear association, P(non-linearity) = 0.005; however, among nonsmokers, there was increased risk even within the 'normal' BMI range. The summary RR for a 10-cm increase in waist circumference was 1.11 (95% CI 1.05-1.18, I(2) = 0%) and for a 0.1-unit increment in waist-to-hip ratio was 1.19 (95% CI 1.09-1.31, I(2) = 11%)., Conclusions: Both general and abdominal fatness increases pancreatic cancer risk. Among nonsmokers, risk increases even among persons within the normal BMI range.

Background: Previous studies of the association between intake of dairy products and colorectal cancer risk have indicated an inverse association with milk, however, the evidence for cheese or other dairy products is inconsistent., Methods: We conducted a systematic review and meta-analysis to clarify the shape of the dose-response relationship between dairy products and colorectal cancer risk. We searched the PubMed database for prospective studies published up to May 2010. Summary relative risks (RRs) were estimated using a random effects model., Results: Nineteen cohort studies were included. The summary RR was 0.83 (95% CI [confidence interval]: 0.78-0.88, I2=25%) per 400 g/day of total dairy products, 0.91 (95% CI: 0.85-0.94, I2=0%) per 200 g/day of milk intake and 0.96 (95% CI: 0.83-1.12, I2=28%) per 50 g/day of cheese. Inverse associations were observed in both men and women but were restricted to colon cancer. There was evidence of a nonlinear association between milk and total dairy products and colorectal cancer risk, P<0.001, and the inverse associations appeared to be the strongest at the higher range of intake., Conclusion: This meta-analysis shows that milk and total dairy products, but not cheese or other dairy products, are associated with a reduction in colorectal cancer risk.

Background: Epidemiologic studies of dietary fat and breast cancer risk are inconsistent, and it has been suggested that a true relation may have been obscured by the imprecise measurement of fat intake., Objective: We examined associations of fat with breast cancer risk by using estimates of fat intake from food diaries and food-frequency questionnaires (FFQs) pooled from 4 prospective studies in the United Kingdom., Design: A total of 657 cases of breast cancer in premenopausal and postmenopausal women were matched on study, age, and recruitment date with 1911 control subjects. Nutrient intakes were estimated from food diaries and FFQs. Conditional logistic regression was used to estimate ORs for breast cancer associated with total, saturated, monounsaturated, and polyunsaturated fat intakes with adjustment for relevant covariates., Results: Neither the food diaries nor the FFQs showed any positive associations between fat intake and overall breast cancer risk. ORs (95% CIs) for the highest compared with lowest quintiles of percentage of energy from total fat were 0.90 (0.66, 1.23) for food diaries and 0.80 (0.59, 1.09) for FFQs., Conclusion: In this study, breast cancer risk was not associated with fat intake in middle-aged women in the United Kingdom, irrespective of whether diet was measured by food diaries or by FFQs.

Introduction: Epidemiologic evidence for an association between colorectal cancer (CRC) risk and total dietary fat, saturated fat (SF), monounsaturated fat (MUFA) and polyunsaturated fat (PUFA) is inconsistent. Previous studies have used food frequency questionnaires (FFQ) to assess diet, but data from food diaries may be less prone to severe measurement error than data from FFQ., Methods: We conducted a case-control study nested within seven prospective UK cohort studies, comprising 579 cases of incident CRC and 1996 matched controls. Standardized dietary data from 4- to 7-day food diaries and from FFQ were used to estimate odds ratios for CRC risk associated with intake of fat and subtypes of fat using conditional logistic regression. We also calculated multivariate measurement error corrected odds ratios for CRC using repeated food diary measurements., Results: We observed no associations between intakes of total dietary fat or types of fat and CRC risk, irrespective of whether dietary data were obtained using food diaries or FFQ., Conclusion: Our results do not support the hypothesis that intakes of total dietary fat, SF, MUFA or PUFA are linked to risk of CRC., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: Gene mutations associated with iron overload have been identified. How food and nutrient intakes affect iron status in persons who may be at risk of iron overload because their genetic status is unknown., Objective: The objective was to determine the relation between food and nutrient intakes, HFE genotype, and iron status. Foods and nutrients associated with iron stores, with adjustment for gene mutations associated with hemochromatosis, were explored., Design: A prospective cohort of women aged 35-69 y (the UK Women's Cohort Study) provided information on diet through a questionnaire and food diary; 6779 women in the cohort provided cheek cell samples, blood samples, or both, which were genotyped for C282Y and H63D mutations, and 2489 women also had their iron status assessed. Relations between serum ferritin and iron intake were investigated by using multiple linear regression, with adjustment for potential confounders., Results: The strongest dietary association with serum ferritin concentration was a positive association with heme iron and not with nonheme or total iron. Weaker positive associations were seen with red and white meat, and negative associations were seen with total energy and white and brown whole-meal bread, independent of genotype and other potential confounders. The effect of genotype on ferritin concentrations primarily occurred after menopause, at which time a strong interaction between genotype and heme iron intake was observed. Other factors associated with serum ferritin concentrations were age, body mass index, blood donation, menopausal status, and HFE genotype., Conclusions: Postmenopausal women eating a diet rich in heme iron and who were C282Y homozygotes had the highest serum ferritin concentrations.