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Background Physical activity has been associated with a significant reduction in risk of sudden cardiac death in epidemiological studies, however, the strength of the association needs clarification. We conducted a systematic review and meta-analysis to summarize the available data from population-based prospective studies. Methods PubMed and Embase databases were searched for studies of physical activity and sudden cardiac death from inception to March 26th 2019. Prospective studies reporting adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) of sudden cardiac death associated with physical activity were included. A random effects model was used to estimate summary RRs (95% CIs). Results Thirteen prospective studies were included in the systematic review. Eight prospective studies with 1193 sudden cardiac deaths among 136,298 participants were included in the meta-analysis of physical activity and sudden cardiac death and the summary RR for highest vs. lowest level of physical activity was 0.52 (95% CI: 0.45–0.60, I2 = 0%, pheterogeneity = 0.72). The association was similar in men and women and among American and European studies. In the dose-response analysis the summary RR was 0.68 (95% CI: 0.55–0.86, I2 = 44%, n = 3) per 20 MET-hours/week. Although the test for nonlinearity was not significant, pnonlinearity = 0.18, there was no further reduction in risk beyond 20–25 MET-hours/week. The summary RR was 0.58 (95% CI: 0.41–0.81, I2 = 0%, pheterogeneity = 0.65, n = 2) for the highest vs. the lowest level of cardiorespiratory fitness. Conclusion This meta-analysis suggest that a high compared to a low level of physical activity may reduce the risk of sudden cardiac death in the general population. Further studies are needed to clarify the dose-response relationship between specific subtypes and intensities of physical activity in relation to sudden cardiac death.

Background: We conducted a systematic literature review and meta-analysis of observational studies investigating adherence to the 2007 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) lifestyle recommendations for cancer prevention and health outcomes. Patients and methods: We searched PubMed and the in-house database of the WCRF Continuous Update Project for publications up to June 2019. Cross-sectional studies were only narratively reviewed given their heterogeneity while findings of cohort/case-control studies were synthesized in umbrella reviews and meta-analyses. Summary relative risks (RRs) and 95% confidence intervals (CI) were estimated using a random-effects model when at least two studies reported results on a specific outcome. Results: Thirty-eight articles (17 prospective, 8 case-control, and 13 cross-sectional studies) were included. The summary RR per each point increment in the 2007 WCRF/AICR score was 0.90 (95% CI: 0.87-0.93, n = 11) for breast cancer, regardless of hormone receptor and menopausal status, 0.86 (95% CI: 0.82-0.89, n = 10) for colorectal cancer, and 0.93 (95% CI: 0.89-0.96, n = 2) for lung cancer risk. No statistically significant associations were reported for prostate (n = 6) and pancreatic cancers (n = 2). Adherence to the recommendations was associated with lower overall mortality (RR = 0.90, 95% CI 0.84-0.96, n = 3) and cancer-specific mortality (RR = 0.91, 95% CI 0.89-0.92; n = 3) in healthy populations, as well as with higher survival in cancer patients (n = 2). In cross-sectional studies, a healthier plasma marker profile and lower cancer risk factors in the general population and a better health status and quality of life in cancer patients/survivors were reported. Conclusions: Adhering to the 2007 WCRF/AICR recommendations is associated with lower risks of cancer incidence, namely breast and colorectal cancers, and mortality. Primary prevention of cancer should emphasize modification of multiple lifestyle factors. Upcoming studies examining the recently updated 2018 guidelines will further clarify such associations., This work was supported by the Biomedical Research Center Network of Epidemiology and Public Health [MS, no grant number] and the World Cancer Research Fund International [grant number 2007/SP01].

Background Adiposity has been associated with elevated risk of urinary incontinence in epidemiological studies; however, the strength of the association has differed between studies. Objectives To conduct a systematic literature review and dose-response meta-analysis of prospective studies on adiposity and risk of urinary incontinence. Search strategy We searched PubMed and Embase databases up to 19 July 2017. Selection criteria Prospective cohort studies were included. Data collection and analysis Data were extracted by one reviewer and checked for accuracy by a second reviewer. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random effects models. Main results Twenty-four prospective studies were included. The summary RR per 5 kg/m2 increment in body mass index (BMI) was 1.20 (95% CI 1.16-1.25, I2 = 62%, n = 11) for population-based studies and 1.19 (95% CI 1.08-1.30, I2 = 87.1%, n = 8) for pregnancy-based studies, 1.18 (95% CI 1.14-1.22, I2 = 0%, n = 2) per 10 cm increase in waist circumference and 1.34 (95% CI 1.11-1.62, I2 = 90%, n = 2) per 10 kg of weight gain. Although the test for nonlinearity was significant for BMI, P = 0.04, the association was approximately linear. For subtypes of urinary incontinence the summary RR per 5 BMI units was 1.45 (95% CI 1.25-1.68, I2 = 85%, n = 3) for frequent incontinence, 1.52 (95% CI 1.37-1.68, I2 = 34%, n = 4) for severe incontinence, 1.33 (95% CI 1.26-1.41, I2 = 0%, n = 8) for stress incontinence, 1.26 (95% CI 1.14-1.40, I2 = 70%, n = 7) for urge incontinence, and 1.52 (95% CI 1.36-1.69, I2 = 0%, n = 3) for mixed incontinence. Conclusion These results suggest excess weight may increase risk of urinary incontinence. Tweetable abstract Overweight and obesity increase the risk of urinary incontinence.

No association between polymorphisms in CYP2E1, GSTM1, NAT1, NAT2 and the risk of gastric adenocarcinoma in the European prospective investigation into cancer and nutrition.

Background Higher body mass index and waist circumference have been associated with increased risk of pancreatitis in several prospective studies; however, the results have not been entirely consistent. Aims We conducted a systematic review and dose-response meta-analysis of prospective studies on adiposity and risk of pancreatitis to clarify this association. Methods PubMed and Embase databases were searched for studies on adiposity and pancreatitis up to January 27, 2020. Prospective studies reporting adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for the association between adiposity and risk of pancreatitis were included, and summary RRs (95% CIs) were calculated using a random effects model. Results Ten prospective studies with 5129 cases and 1,693,657 participants were included. The summary RR (95% CI) of acute pancreatitis was 1.18 (95% CI: 1.03–1.35, I2 = 91%, n = 10 studies) per 5 kg/m2 increase in BMI and 1.36 (95% CI: 1.29–1.43, I2 = 0%, n = 3) per 10 cm increase in waist circumference. There was evidence of a nonlinear association between BMI and acute pancreatitis, pnonlinearity

A diagnosis of primary sclerosing cholangitis (PSC) has been associated with increased risk of hepatobiliary cancers, colorectal cancer and all-cause mortality in several studies, while associations with cardiovascular disease have been inconsistent. We conducted a systematic review and meta-analysis of published cohort studies on the topic to summarize these associations. PubMed and Embase databases were searched up to January 13th, 2020. Cohort studies on PSC and risk of cancer, cardiovascular disease, or mortality were included. Summary relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using random effects models. The summary RR (95% CI) comparing persons with PSC to persons without PSC was 584.37 (269.42–1267.51, I2 = 89%, n = 4) for cholangiocarcinoma (CCA), 155.54 (125.34–193.02, I2 = 0%, n = 3) for hepatobiliary cancer, 30.22 (11.99–76.17, I2 = 0%, n = 2) for liver cancer, 16.92 (8.73–32.78, I2 = 88%, n = 4) for gastrointestinal cancer, 7.56 (2.42–23.62, I2 = 0%, n = 3) for pancreatic cancer, 6.10 (4.19–8.87, I2 = 14%, n = 7) for colorectal cancer (CRC), 4.13 (2.99–5.71, I2 = 80%, n = 5) for total cancer, 3.55 (2.94–4.28, I2 = 46%, n = 5) for all-cause mortality, and 1.57 (0.25–9.69, I2 = 79%, n = 2) for cardiovascular disease. Strong positive associations were observed between PSC and risk of CCA, hepatobiliary cancer, liver cancer, gastrointestinal cancer, pancreatic cancer, CRC, total cancer, and all-cause mortality, but not for cardiovascular disease.

The association between physical activity and risk of abdominal aortic aneurysm has been inconsistent with some studies reporting a reduced risk while others have found no association. We conducted a systematic review and meta-analysis of prospective studies to quantify the association. PubMed and Embase databases were searched up to 3 October 2020. Prospective studies were included if they reported adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) of abdominal aortic aneurysm associated with physical activity. Summary RRs (95% CIs) were estimated using a random effects model. Nine prospective studies (2073 cases, 409,732 participants) were included. The summary RR for high vs. low physical activity was 0.70 (95% CI: 0.56–0.87, I2 = 58%) and per 20 metabolic equivalent task (MET)-hours/week increase of activity was 0.84 (95% CI: 0.74–0.95, I2 = 59%, n = 6). Although the test for nonlinearity was not significant (p = 0.09) the association appeared to be stronger when increasing the physical activity level from 0 to around 20–25 MET-hours/week than at higher levels. The current meta-analysis suggest that higher physical activity may reduce the risk of abdominal aortic aneurysm, however, further studies are needed to clarify the dose–response relationship between different subtypes and intensities of activity and abdominal aortic aneurysm risk.

Although physical activity is an established protective factor for cardiovascular diseases such as ischemic heart disease and stroke, less is known with regard to the association between specific domains of physical activity and heart failure, as well as the association between cardiorespiratory fitness and heart failure. We conducted a systematic review and meta-analysis of prospective observational studies to clarify the relations of total physical activity, domains of physical activity and cardiorespiratory fitness to risk of heart failure. PubMed and Embase databases were searched up to January 14th, 2020. Summary relative risks (RRs) were calculated using random effects models. Twenty-nine prospective studies (36 publications) were included in the review. The summary RRs for high versus low levels were 0.77 (95% CI 0.70–0.85, I2 = 49%, n = 7) for total physical activity, 0.74 (95% CI 0.68–0.81, I2 = 88.1%, n = 16) for leisure-time activity, 0.66 (95% CI 0.59–0.74, I2 = 0%, n = 2) for vigorous activity, 0.81 (95% CI 0.69–0.94, I2 = 86%, n = 3) for walking and bicycling combined, 0.90 (95% CI 0.86–0.95, I2 = 0%, n = 3) for occupational activity, and 0.31 (95% CI 0.19–0.49, I2 = 96%, n = 6) for cardiorespiratory fitness. In dose–response analyses, the summary RRs were 0.89 (95% CI 0.83–0.95, I2 = 67%, n = 4) per 20 MET-hours per day of total activity and 0.71 (95% CI 0.65–0.78, I2 = 85%, n = 11) per 20 MET-hours per week of leisure-time activity. Nonlinear associations were observed in both analyses with a flattening of the dose–response curve at 15–20 MET-hours/week for leisure-time activity. These findings suggest that high levels of total physical activity, leisure-time activity, vigorous activity, occupational activity, walking and bicycling combined and cardiorespiratory fitness are associated with reduced risk of developing heart failure.

Background Diabetes mellitus has been associated with increased risk of pancreatitis in several studies, however, not all studies have found an association. We conducted a systematic review and meta-analysis of prospective studies on diabetes mellitus and pancreatitis to clarify the association. Methods PubMed and Embase databases were searched for studies on diabetes mellitus and pancreatitis up to 8th of January 2020. Cohort studies that reported adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for the association between diabetes diagnosis and pancreatitis were included and summary RRs (95% CIs) were calculated using a random effects model. Results Eight cohort studies were included in the meta-analysis, and seven of these were included in the analysis of diabetes mellitus and acute pancreatitis (14124 cases, 5.7 million participants). Comparing diabetes patients with persons without diabetes the summary RRs (95% CIs) were 1.74 (95% CI: 1.33–2.29, I2 = 95%) for acute pancreatitis, 1.40 (95% CI: 0.88–2.22, I2 = 0%, n = 2) for chronic pancreatitis, and 1.39 (95% CI: 1.07–1.80, I2 = 54%, n = 3) for pancreatitis overall. Although there was some indication of publication bias in the analysis of acute pancreatitis this appeared to be explained by one outlying study which when excluded did not substantially alter the association. The results persisted in several subgroup and sensitivity analyses. Conclusions These results suggest that diabetes patients are at an increased risk of acute pancreatitis. Further studies are needed on diabetes and risk of chronic pancreatitis, pancreatitis overall and on gallstone-related and non-gallstone-related pancreatitis.

BACKGROUND AND AIM: The strength of the association between diabetes and risk of heart failure has differed between previous studies and the available studies have not been summarized in a meta-analysis. We therefore quantified the association between diabetes and blood glucose and heart failure in a systematic review and meta-analysis. METHODS AND RESULTS: PubMed and Embase databases were searched up to May 3rd 2018. Prospective studies on diabetes mellitus or blood glucose and heart failure risk were included. A random effects model was used to calculate summary relative risks (RRs) and 95% confidence intervals (CIs). Seventy seven studies were included. Among the population-based prospective studies, the summary RR for individuals with diabetes vs. no diabetes was 2.06 (95% CIs: 1.73-2.46, I2 = 99.8%, n = 30 studies, 401495 cases, 21416780 participants). The summary RR was 1.23 (95% CI: 1.15-1.32, I2 = 78.2%, n = 10, 5344 cases, 91758 participants) per 20 mg/dl increase in blood glucose and there was evidence of a J-shaped association with nadir around 90 mg/dl and increased risk even within the pre-diabetic blood glucose range. Among the patient-based studies the summary RR was 1.69 (95% CI: 1.57-1.81, I2 = 85.5%, pheterogeneity613925 participants) and 1.25 (95% CI: 0.89-1.75, I2 = 95.6%, pheterogeneity

Background We conducted a systematic review and meta-analysis to clarify the association between smoking and the risk of developing heart failure. Methods PubMed and Embase databases were searched up to 24 July 2018. Prospective studies were included if they reported adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) of heart failure associated with smoking. Summary RRs and 95% CIs were estimated using a random effects model. Results Twenty-six studies were included. The summary RR was 1.75 (95% CI: 1.54–1.99, I2 = 81%, n = 10) for current smokers, 1.16 (95% CI: 1.08–1.24, I2 = 51%, n = 9) for former smokers, and 1.44 (1.34–1.55, I2 = 83%, n = 10) for ever smokers compared with never smokers. The summary RR was 1.41 (95% CI: 1.01–1.96, I2 = 82%, n = 2) per 10 cigarettes per day, 1.11 (95% CI: 1.04–1.18, I2 = 70%, n = 3) and 1.08 (95% CI: 1.02–1.14, I2 = 34%, n = 2) per 10 pack-years among ever smokers and former smokers, respectively, and 0.79 (95% CI: 0.63–1.00, I2 = 96%, n = 2) per 10 years since quitting smoking. The association between smoking cessation and heart failure reached significance at 15 years of smoking cessation, and at 30 years the summary RR was 0.72 (95% CI: 0.57–0.90), only slightly higher than the summary RR for never smokers (0.64 (95% CI: 0.57–0.72)) when compared with current smokers. Conclusion Smoking is associated with increased risk of heart failure, but the risk decreases with increasing duration since smoking cessation. Any further studies should investigate the association between number of cigarettes per day, duration, pack-years and time since quitting smoking and risk of heart failure.

Background and aim: Colorectal cancer [CRC] is highly prevalent worldwide, with dietary habits being a major risk factor. We systematically reviewed and meta-analysed the observational evidence on the association between CRC and dietary patterns [DP] derived from Principal Component Analysis. Design: PRISMA guidelines were followed. Web of Science, Medline/PubMed, EMBASE, and The Cochrane Library were searched to identify all eligible papers published up to July 2017. Any pre-defined cancer in the colon was included, namely colon-rectal cancer (CRC), colon cancer (CC), rectal cancer (RC), or proximal and distal CC, if available. Western (WDP) and prudent (PDP) dietary patterns were compared as a proxy to estimate ‘unhealthy’ (Rich in meat and processed foods) and ‘healthy’ diets (containing fruits or vegetables), respectively. Meta-analyses were carried out using random effects model to calculate overall risk estimates. Relative risks (RR) and 95% confidence intervals were estimated comparing the highest versus the lowest categories of dietary patterns for any of the forms of colon cancer studied. Results: 28 studies were meta-analysed. A WDP was associated with increased risk of CRC (RR 1.25; 95% CI 1.11, 1.40), and of CC (RR 1.30; 95% CI 1.11, 1.52). A PDP was negatively associated with CRC (RR 0.81; 95% CI 0.73, 0.91). Sensitivity analyses showed that individuals from North- and South- American countries had a significantly higher risk of CRC than those from other continents. Conclusion: A PDP might reduce the risk of CRC. Conversely, a WDP is associated with a higher risk of disease.

We conducted a systematic review and meta-analysis to clarify the association between adiposity, diabetes, and physical activity and the risk of kidney stones. PubMed and Embase were searched up to April 22nd 2018 for relevant studies. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random effects models. Thirteen cohort studies were included. The summary relative risk was 1.21 (95% CI 1.12–1.30, I2 = 76%, n = 8) per 5 unit increment in BMI, 1.16 (95% CI 1.12–1.19, I2 = 0%, n = 5) per 10 cm increase in waist circumference, 1.06 (95% CI 1.04–1.08, I2 = 67%, n = 3) per 5 kg increase in weight and 1.12 (95% CI 1.06–1.18, I2 = 86%, n = 3) per 5 kg of weight gain. The summary RR was 1.16 (95% CI 1.03–1.31, I2 = 51%, n = 10) for participants with diabetes compared to participants without diabetes, and 0.93 (95% CI 0.78–1.10, I2 = 80%, n = 4) for high vs. low physical activity. These results suggest a positive association between adiposity and diabetes and the risk of kidney stones, but no association with physical activity. Electronic supplementary material The online version of this article (10.1007/s10654-018-0426-4) contains supplementary material, which is available to authorized users.

Smoking is an established risk factor for cardiovascular disease including coronary heart disease and stroke, however, data regarding smoking and sudden cardiac death have not been summarized in a meta-analysis previously. We therefore conducted a systematic review and meta-analysis to clarify this association. We searched the PubMed and Embase databases for studies of smoking and sudden cardiac death up to July 20th 2017. Prospective studies were included if they reported adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for smoking and sudden cardiac death. Summary RRs were estimated by use of a random effects model. Twelve prospective studies were included. The summary RR was 3.06 (95% CI 2.46–3.82, I2 = 41%, pheterogeneity = 0.12, n = 7) for current smokers and 1.38 (95% CI 1.20–1.60, I2 = 0%, pheterogeneity = 0.55, n = 7) for former smokers compared to never smokers. For four studies using non-current (never + former) smokers as the reference category the summary RR among current smokers was 2.08 (95% CI 1.70–2.53, I2 = 18%, pheterogeneity = 0.30). The results persisted in most of the subgroup analyses. There was no evidence of publication bias. These results confirm that smoking increases the risk of sudden cardiac death. Any further studies should investigate in more detail the effects of duration of smoking, number of cigarettes per day, pack-years, and time since quitting smoking and sudden cardiac death. Electronic supplementary material The online version of this article (10.1007/s10654-017-0351-y) contains supplementary material, which is available to authorized users.

Although overweight and obesity are established risk factors for some types of heart disease including ischemic heart disease, heart failure and atrial fibrillation, less is known about the association between adiposity and sudden cardiac death. We conducted a systematic review and meta-analysis of prospective studies to clarify the association between adiposity and risk of sudden cardiac death. PubMed and Embase databases were searched up to July 20th 2017. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random effects models. The summary RR was 1.16 (95% CI 1.05–1.28, I2 = 68%, n = 14) per 5 unit increment in BMI, and 1.82 (95% CI 1.61–2.07, I2 = 0%, n = 3) per 0.1 unit increase in waist-to-hip ratio, and 1.03 (95% CI 0.93–1.15, I2 = 0%, n = 2) per 10 cm increase in waist circumference. The heterogeneity in the analysis of BMI and sudden cardiac death persisted across most subgroup analyses. The association was stronger among studies with longer follow-up compared to short follow-up and was observed in the European and American studies, but not in the Asian studies. There was a J-shaped association between BMI and sudden cardiac death and the lowest risk was observed in the normal weight range, however, the increased risk with a low BMI was attenuated among studies with a longer duration of follow-up. This meta-analysis suggest an increased risk of sudden cardiac death with increasing BMI and waist-to-hip ratio, however, further studies with stratification for smoking status are needed of waist circumference, weight changes and adiposity at younger ages. Electronic supplementary material The online version of this article (10.1007/s10654-017-0353-9) contains supplementary material, which is available to authorized users.

Evidence from in vivo, in vitro and ecological studies are suggestive of a protective effect of vitamin D against pancreatic cancer (PC). However, this has not been confirmed by analytical epidemiological studies. We aimed to examine the association between pre-diagnostic circulating vitamin D concentrations and PC incidence in European populations. We conducted a pooled nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nord-Trondelag Health Study's second survey (HUNT2) cohorts. In total, 738 primary incident PC cases (EPIC n = 626; HUNT2 n = 112; median follow-up = 6.9 years) were matched to 738 controls. Vitamin D [25(OH)D2 and 25(OH)D3 combined] concentrations were determined using isotope-dilution liquid chromatography-tandem mass spectrometry. Conditional logistic regression models with adjustments for body mass index and smoking habits were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95%CI). Compared with a reference category of >50 to 75 nmol/L vitamin D, the IRRs (95% CIs) were 0.71 (0.42-1.20); 0.94 (0.72-1.22); 1.12 (0.82-1.53) and 1.26 (0.79-2.01) for clinically pre-defined categories of ≤25; >25 to 50; >75 to 100; and >100 nmol/L vitamin D, respectively (p for trend = 0.09). Corresponding analyses by quintiles of season-standardized vitamin D concentrations also did not reveal associations with PC risk (p for trend = 0.23). Although these findings among participants from the largest combination of European cohort studies to date show increasing effect estimates of PC risk with increasing pre-diagnostic concentrations of vitamin D, they are not statistically significant.

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.

Purpose There is no published dose–response meta-analysis on the association between height and colorectal cancer risk (CRC) by sex and anatomical sub-site. We conducted a meta-analysis of prospective studies on the association between height and CRC risk with subgroup analysis and updated evidence on the association between body fatness and CRC risk. Methods PubMed and several other databases were searched up to November 2016. A random effects model was used to calculate dose–response summary relative risks (RR’s). Results 47 studies were included in the meta-analyses including 50,936 cases among 7,393,510 participants. The findings support the existing evidence regarding a positive association of height, general and abdominal body fatness and CRC risk. The summary RR were 1.04 [95% (CI)1.02–1.05, I² = 91%] per 5 cm increase in height, 1.02 [95% (CI)1.01–1.02, I² = 0%] per 5 kg increase in weight, 1.06 [95% (CI)1.04–1.07, I² = 83%] per 5 kg/m2 increase in BMI, 1.02 [95% (CI)1.02–1.03, I² = 4%] per 10 cm increase in waist circumference, 1.03 [95% (CI)1.01–1.05, I² = 16%] per 0.1 unit increase in waist to hip ratio. The significant association for height and CRC risk was similar in men and women. The significant association for BMI and CRC risk was stronger in men than in women. Conclusion The positive association between height and risk of CRC suggests that life factors during childhood and early adulthood might play a role in CRC aetiology. Higher general and abdominal body fatness during adulthood are risk factors of CRC and these associations are stronger in men than in women. Electronic supplementary material The online version of this article (doi:10.1007/s00394-017-1557-1) contains supplementary material, which is available to authorized users.

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; I 2 :43%, N =9 studies, cases=5,507) 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%; I 2 :65%, N =7 studies). Although there was indication of non-linearity ( Pnon-linearity

Different adiposity measures have been associated with increased risk of atrial fibrillation, however, results have previously only been summarized for BMI. We therefore conducted a systematic review and meta-analysis of prospective studies to clarify the association between different adiposity measures and risk of atrial fibrillation. PubMed and Embase databases were searched up to October 24th 2016. Summary relative risks (RRs) were calculated using random effects models. Twenty-nine unique prospective studies (32 publications) were included. Twenty-five studies (83,006 cases, 2,405,381 participants) were included in the analysis of BMI and atrial fibrillation. The summary RR was 1.28 (95% confidence interval: 1.20–1.38, I2 = 97%) per 5 unit increment in BMI, 1.18 (95% CI: 1.12–1.25, I2 = 73%, n = 5) and 1.32 (95% CI: 1.16–1.51, I2 = 91%, n = 3) per 10 cm increase in waist and hip circumference, respectively, 1.09 (95% CI: 1.02–1.16, I2 = 44%, n = 4) per 0.1 unit increase in waist-to-hip ratio, 1.09 (95% CI: 1.02–1.16, I2 = 94%, n = 4) per 5 kg increase in fat mass, 1.10 (95% CI: 0.92–1.33, I2 = 90%, n = 3) per 10% increase in fat percentage, 1.10 (95% CI: 1.08–1.13, I2 = 74%, n = 10) per 5 kg increase in weight, and 1.08 (95% CI: 0.97–1.19, I2 = 86%, n = 2) per 5% increase in weight gain. The association between BMI and atrial fibrillation was nonlinear, p nonlinearity

Background Tobacco smoking has been associated with increased risk of pancreatitis in several studies, however, not all studies have found an association and it is unclear whether there is a dose-response relationship between increasing amount of tobacco smoked and pancreatitis risk. We conducted a systematic review and meta-analysis of prospective studies on tobacco smoking and pancreatitis to clarify the association. Methods PubMed and Embase databases were searched for relevant studies up to April 13th, 2019. Prospective studies that reported adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for the association between tobacco smoking and pancreatitis were included and summary RRs were calculated using a random effects model. Results Ten prospective studies were included. The summary RR for acute pancreatitis was 1.49 (95% CI: 1.29–1.72, I2 = 68%, n = 7) for current smokers, 1.24 (95% CI: 1.15–1.34, I2 = 0%, n = 7) for former smokers, and 1.39 (95% CI: 1.25–1.54, I2 = 69%, n = 7) for ever smokers compared to never smokers. Similar results were observed for chronic pancreatitis and acute/chronic pancreatitis combined. The summary RR per 10 cigarettes per day was 1.30 (95% CI: 1.18–1.42, I2 = 42%, n = 3) and per 10 pack-years in current smokers was 1.13 (95% CI: 1.08–1.17, I2 = 14%, n = 4) for acute pancreatitis and results were similar for chronic pancreatitis and acute/chronic pancreatitis combined. Conclusions These results suggest that tobacco smoking increases the risk of acute and chronic pancreatitis and acute and chronic pancreatitis combined and that there is a dose-response relationship between increasing number of cigarettes and pack-years and pancreatitis risk.

Purpose The purpose of the present study was to systematically review the complex associations between energy balance-related factors and breast cancer risk, for which previous evidence has suggested different associations in the life course of women and by hormone receptor (HR) status of the tumor. Methods Relevant publications on adulthood physical activity, sedentary behavior, body mass index (BMI), waist and hip circumferences, waist-to-hip ratio, and weight change and pre- and postmenopausal breast cancer risk were identified in PubMed up to 30 April 2017. Random-effects meta-analyses were conducted to summarize the relative risks across studies. Results One hundred and twenty-six observational cohort studies comprising over 22,900 premenopausal and 103,000 postmenopausal breast cancer cases were meta-analyzed. Higher physical activity was inversely associated with both pre- and postmenopausal breast cancers, whereas increased sitting time was positively associated with postmenopausal breast cancer. Although higher early adult BMI (ages 18–30 years) was inversely associated with pre- and postmenopausal breast cancers, adult weight gain and greater body adiposity increased breast cancer risk in postmenopausal women, and the increased risk was evident for HR+ but not HR− breast cancers, and among never but not current users of postmenopausal hormones. The evidence was less consistent in premenopausal women. There were no associations with adult weight gain, inverse associations with adult BMI (study baseline) and hip circumference, and non-significant associations with waist circumference and waist-to-hip ratio that were reverted to positive associations on average in studies accounting for BMI. No significant associations were observed for HR-defined premenopausal breast cancers. Conclusion Better understanding on the impact of these factors on pre- and postmenopausal breast cancers and their subtypes along the life course is needed.

Background A high intake of dietary fibre has been associated with a reduced risk of diverticular disease in several studies; however, the dose–response relationship between fibre intake and diverticular disease risk has varied, and the available studies have not been summarised in a meta-analysis. We conducted a systematic review and meta-analysis of prospective cohort studies to clarify the association between dietary fibre intake, fibre subtypes, and the risk of diverticular disease. Methods PubMed and Embase databases were searched up to August 9th 2018. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model and nonlinear associations were modelled using fractional polynomial models. Results Five prospective cohort studies with 19,282 cases and 865,829 participants were included in the analysis of dietary fibre and diverticular disease risk. The summary RR was 0.74 (95% CI 0.71–0.78, I2 = 0%) per 10 g/day. There was no evidence of a nonlinear association between dietary fibre intake and diverticular disease risk, pnonlinearity = 0.35, and there was a 23%, 41% and 58% reduction in risk for an intake of 20, 30, and 40 g/day, respectively, compared to 7.5 g/day. There was no evidence of publication bias with Egger’s test, p = 0.58 and the association persisted in subgroup and sensitivity analyses. The summary RR per 10 g/day was 0.74 (95% CI 0.67–0.81, I2 = 60%, n = 4) for cereal fibre, 0.56 (95% CI 0.37–0.84, I2 = 73%, n = 2) for fruit fibre, and 0.80 (95% CI 0.45–1.44, I2 = 87%, n = 2) for vegetable fibre. Conclusions These results suggest that a high fibre intake may reduce the risk of diverticular disease and individuals consuming 30 g of fibre per day have a 41% reduction in risk compared to persons with a low fibre intake. Further studies are needed on fibre types and risk of diverticular disease and diverticulitis. Electronic supplementary material The online version of this article (10.1007/s00394-019-01967-w) contains supplementary material, which is available to authorized users.

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 18–21years) 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 5kg/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.

Background— Obesity has been associated with increased risk of heart failure, but whether overweight also increases risk is unclear. It is also unclear whether abdominal adiposity is more strongly associated with heart failure risk than general adiposity. We conducted a systematic review and meta-analysis of prospective studies to clarify the strength and shape of the dose-response relationship between general and abdominal adiposity and the risk of heart failure. Methods and Results— PubMed and Embase databases were searched up to October 10, 2014. Summary relative risks were calculated using random-effects models. A total of 28 studies (27 publications) were included. Twenty-three prospective studies with >15 905 incident cases among 647 388 participants were included in the analysis of body mass index and heart failure incidence, and 4 studies were included for heart failure mortality. The summary relative risk for a 5-unit increment in body mass index was 1.41 (95% confidence interval, 1.34–1.47; I 2 =83%) for heart failure incidence and 1.26 (95% confidence interval, 0.85–1.87; I 2 =95%) heart failure mortality. Although the test for nonlinearity was significant ( P 2 ; however, there was evidence of increased risk even in the overweight body mass index range. The summary relative risk for a 10-cm increase in waist circumference was 1.29 (95% confidence interval, 1.21–1.37; I 2 =89%) and per 0.1-unit increase in waist-to-hip ratio was 1.29 (95% confidence interval, 1.13–1.47; I 2 =82%). Conclusion— Overweight and obesity and abdominal adiposity are associated with increased risk of heart failure.

Background Diabetes mellitus has been associated with reduced risk of abdominal aortic aneurysm in a number of epidemiological studies, however, until recently little data from prospective studies have been available. We therefore conducted a systematic review and meta-analysis of prospective studies to quantify the association. Material and methods Two investigators searched the PubMed and Embase databases for studies of diabetes and abdominal aortic aneurysm up to May 8th 2018. Prospective studies were included if they reported adjusted relative risk (RR) estimates and 95% confidence intervals (95% CIs) of abdominal aortic aneurysm associated with a diabetes diagnosis. Summary relative risks were estimated by use of a random effects model. Results We identified 16 prospective studies with 16,572 cases among 4,563,415 participants that could be included in the meta-analysis. The summary RR for individuals with diabetes compared to individuals without diabetes was 0.58 (95% CI: 0.51–0.66, I2 = 40.4%, pheterogeneity = 0.06). The results persisted when stratified by sex, duration of follow-up, and in most of the other subgroup analyses. There was no evidence of publication bias with Egger's test, p = 0.64 or by inspection of the funnel plots. Conclusions These results suggest that individuals with diabetes mellitus are at a reduced risk of abdominal aortic aneurysm, however, whether pharmacological agents for diabetes mellitus explain this observation needs to be clarified in future studies.

Background Epidemiological studies on smoking and atrial fibrillation have been inconsistent, with some studies showing a positive association while others have found no association. It is also unclear whether there is a dose–response relationship between the number of cigarettes smoked or pack-years and the risk of atrial fibrillation. We conducted a systematic review and meta-analysis to clarify the association. Design Systematic review and meta-analysis. Methods We searched the PubMed and Embase databases for studies of smoking and atrial fibrillation up to 20 July 2017. Prospective studies and nested case–control studies within cohort studies reporting adjusted relative risk estimates and 95% confidence intervals (CIs) of atrial fibrillation associated with smoking were included. Summary relative risks (95% CIs) were estimated using a random effects model. Results Twenty nine prospective studies (22 publications) were included. The summary relative risk was 1.32 (95% CI 1.12–1.56, I2 = 84%, n = 11 studies) for current smokers, 1.09 (95% CI 1.00–1.18, I2 = 33%, n = 9) for former smokers and 1.21 (95% CI 1.12–1.31, I2 = 80%, n = 14) for ever smokers compared to never smokers. Comparing current versus non-current smokers the summary relative risk was 1.33 (95% CI 1.14–1.56, I2 = 78%, n = 10). The summary relative risk was 1.14 (95% CI 1.10–1.20, I2 = 0%, n = 3) per 10 cigarettes per day and 1.16 (95% CI 1.09–1.25, I2 = 49%, n = 2) per 10 pack-years and there was no evidence of a non-linear association for cigarettes per day, Pnon-linearity = 0.17. Conclusions The current meta-analysis suggests that smoking is associated with an increased risk of atrial fibrillation in a dose-dependent matter, but the association is weaker among former smokers compared to current smokers.

Greater body mass index (BMI) has been associated with increased risk of psoriasis in case–control and cross-sectional studies, however, the evidence from prospective studies has been limited. We conducted a systematic review and dose–response meta-analysis of different adiposity measures and the risk of psoriasis to provide a more robust summary of the evidence based on data from prospective studies. PubMed and Embase databases were searched for relevant studies up to August 8th 2017. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random effects model. The summary relative risk (RR) for a 5 unit increment in BMI was 1.19 (95% CI 1.10–1.28, I2 = 83%, n = 7). The association appeared to be stronger at higher compared to lower levels of BMI, pnonlinearity < 0.0001, and the lowest risk was observed at a BMI around 20. The summary RR was 1.24 (95% CI 1.17–1.31, I2 = 0%, pheterogeneity = 0.72, n = 3) per 10 cm increase in waist circumference, 1.37 (95% CI 1.23–1.53, I2 = 0%, pheterogeneity = 0.93, n = 3) per 0.1 unit increase in waist-to-hip ratio, and 1.11 (95% CI 1.07–1.16, I2 = 47%, pheterogeneity = 0.15, n = 3) per 5 kg of weight gain. Adiposity as measured by BMI, waist circumference, waist-to-hip ratio, and weight gain is associated with increased risk of psoriasis. Open AccessThis article is distributed under the terms of the CreativeCommons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, dis-tribution, and reproduction in any medium, provided you giveappropriate credit to the original author(s) and the source, provide alink to the Creative Commons license, and indicate if changes weremade

We conducted a systematic literature review to explore the association between circulating C-reactive protein (CRP), a low-grade inflammation biomarker, and breast cancer risk. Relevant prospective studies in women were identified in PubMed and Web of Science until February 2015. Random-effects dose–response meta-analysis was conducted, overall and in postmenopausal women. Twelve out of 15 studies identified were included in the meta-analysis on any breast cancers (3,522 cases; 69,610 women) and nine on postmenopausal breast cancer (2,516 cases; 36,847 women). For each doubling of CRP concentration, a 7% [95% confidence interval (CI), 2%–12%] and 6% (95% CI, 1%–11%) increased risk was observed (I2 = 47% and 32%; Pheterogeneity = 0.04 and 0.17), respectively. The association was linear over most of the range of CRP concentrations. Positive associations remained in the studies that examined the exclusion of early years of follow-up. Associations were attenuated in studies adjusted for lifestyle factors, which partly explained the significant heterogeneity between studies in the overall analysis. On average, the associations in studies adjusted or not adjusted for body mass index were similar. Low-grade inflammation may have a role in breast cancer development. Additional prospective studies are needed to better understand confounding and effect modification from lifestyle factors. Cancer Epidemiol Biomarkers Prev; 24(10); 1439–49. ©2015 AACR.

Background Although diabetes mellitus is an established risk factor for myocardial infarction and stroke, data on the association with sudden cardiac death are less extensive and the findings have not been entirely consistent. We therefore conducted a systematic review and meta-analysis of prospective studies on diabetes mellitus and risk of sudden cardiac death. Methods and results PubMed and Embase databases were searched up to July 18th 2017. Prospective studies that reported adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for the association between a diabetes diagnosis or pre-diabetes and risk of sudden cardiac death were included. Summary RRs were estimated by use of a random effects model. Nineteen population-based prospective studies (11 publications) (3610 cases, 249,225 participants) and 10 patient-based prospective studies (2713 cases, 55,098 participants) were included. The summary RR for diabetes patients vs. persons without diabetes was 2.02 (95% CI: 1.81–2.25, I2 = 0%, pheterogeneity = 0.91) in the population-based studies. The summary RR was 1.23 (95% CI: 1.05–1.44, I2 = 6%, pheterogeneity = 0.34) for the association between pre-diabetes and sudden cardiac death (n = 3 studies, 1000 sudden cardiac deaths, 18,360 participants). In the patient-based studies, the summary RR of sudden cardiac death for diabetes patients vs. patients without diabetes was 1.75 (95% CI: 1.51–2.03, I2 = 39%, pheterogeneity = 0.10) for all patients combined, 1.63 (95% CI: 1.36–1.97, I2 = 39%, n = 5) for coronary heart disease patients, and 1.85 (95% CI: 1.48–2.33, I2 = 0%, n = 3) for heart failure patients. Conclusions These results suggest that diabetes patients are at an increased risk of sudden cardiac death both in the general population and among different patient groups.

Improvements in colorectal cancer (CRC) detection and treatment have led to greater numbers of CRC survivors, for whom there is limited evidence on which to provide dietary guidelines to improve survival outcomes. Higher intake of red and processed meat and lower intake of fibre are associated with greater risk of developing CRC, but there is limited evidence regarding associations with survival after CRC diagnosis. Among 3789 CRC cases in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, pre-diagnostic consumption of red meat, processed meat, poultry and dietary fibre was examined in relation to CRC-specific mortality (n 1008) and all-cause mortality (n 1262) using multivariable Cox regression models, adjusted for CRC risk factors. Pre-diagnostic red meat, processed meat or fibre intakes (defined as quartiles and continuous grams per day) were not associated with CRC-specific or all-cause mortality among CRC survivors; however, a marginal trend across quartiles of processed meat in relation to CRC mortality was detected (P 0·053). Pre-diagnostic poultry intake was inversely associated with all-cause mortality among women (hazard ratio (HR)/20 g/d 0·92; 95 % CI 0·84, 1·00), but not among men (HR 1·00; 95 % CI 0·91, 1·09) (P for heterogeneity=0·10). Pre-diagnostic intake of red meat or fibre is not associated with CRC survival in the EPIC cohort. There is suggestive evidence of an association between poultry intake and all-cause mortality among female CRC survivors and between processed meat intake and CRC-specific mortality; however, further research using post-diagnostic dietary data is required to confirm this relationship., The coordination of EPIC is financially supported by the European Commission (Directorate General for Health and Consumer Affairs; DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale and Institut National de la Santé et de la Recherche Médicale (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro (AIRC) and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund and Statistics Netherlands (The Netherlands); Nordic Center of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra and ISCIII RETIC (Instituto de Salud Carlos III Las Redes temáticas de investigación cooperativa en salud) (RD06/0020) (Spain); World Cancer Research Foundation ref. 2011/428, AGAUR (Agency for Management of University and Research Grants), Generalitat de Catalunya (exp. 2014 SGR 726), Health Research Funds (FIS Exp PI11/1486) and RD12/0036/0018 and Catalan Institute of Oncology (ICO-IDIBELL)(Barcelona); Swedish Cancer Society, Swedish Scientific Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 to EPIC-Oxford) and Medical Research Council (1000143 to EPIC-Norfolk) (UK).

BACKGROUND: Emerging evidence from cohort studies indicates that adiposity is associated with greater incidence of head and neck cancer (HNC). However, most studies have used self-reported anthropometry which is prone to error. METHODS: Among 363 094 participants in the European Prospective Investigation into Cancer and Nutrition study (EPIC) with measured anthropometry, there were 837 incident cases of HNC. HNC risk was examined in relation to body mass index (BMI) [lean: < 22.5 kg/m², normal weight (reference): 22.5-24.9 kg/m², overweight 25-29.9 kg/m², obese: > 30 kg/m²], waist circumference (WC), hip circumference (HC) and waist to hip ratio (WHR) using Cox proportional hazards models. RESULTS: Among men, a BMI < 22.5 kg/m² was associated with higher HNC risk [hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.23 - 2.12)]; BMI was not associated with HNC among women. WC and WHR were associated with greater risk of HNC among women, (WC per 5 cm: HR 1.08, 95% CI 1.02 - 1.15; WHR per 0.1 unit: HR 1.64, 95% CI 1.38 - 1.93). After stratification by smoking status, the association for WHR was present only among smokers (p interaction 0.004). Among men, WC and WHR were associated with HNC only upon additional adjustment for BMI (WC per 5 cm: HR 1.16, 95% CI 1.07 - 1.26; WHR per 0.1 unit: HR 1.42, 95% CI 1.21 - 1.65). CONCLUSION: Central adiposity, particularly among women, may have a stronger association with HNC risk than previously estimated. IMPACT: Strategies to reduce obesity may beneficially impact HNC incidence., The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC- 2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada; , PI13/01162 to EPIC-Murcia), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to K.T. Khaw, N.J. Wareham; C570/A16491 to R.C. Travis and C8221/A19170 to Tim Key (EPIC-Oxford), Medical Research Council (1000143 to K.T. Khaw, N.J. Wareham, MR/M012190/1 to Tim Key (EPIC-Oxford)) (United Kingdom).

Purpose We conducted a systematic review and meta-analysis of prospective studies of the association between body mass index (BMI) and physical activity and diverticular disease risk. Methods PubMed and Embase databases were searched up to February 7, 2017. Summary relative risks and 95% confidence intervals (95% CIs) were calculated using a random effects model and nonlinear associations were modeled using fractional polynomial models. Results Six cohort studies of BMI and diverticular disease risk (28,915 cases, 1,636,777 participants) and five cohort studies of physical activity and diverticular disease risk (2080 cases, 147,869 participants) were included. The summary relative risk (RR) of incident diverticular disease for a 5 unit BMI increment was 1.28 (95% CI: 1.18–1.40, I 2 = 77%, n = 6) for diverticular disease, 1.31 (95% CI: 1.09–1.56, I 2 = 74%, n = 2) for diverticulitis, and 1.20 (95% CI: 1.04–1.40, I 2 = 56%, n = 3) for diverticular disease complications. There was no evidence of a nonlinear association between BMI and diverticular disease risk (p nonlinearity = 0.22), and risk increased even within the normal weight range. Compared to a BMI of 20, the summary RR for a BMI of 22.5, 25.0, 27.5, 30.0, 32.5, 35.0, 37.5, and 40.0 was 1.15 (1.07–1.23), 1.31 (1.17–1.47), 1.50 (1.31–1.71), 1.71 (1.52–1.94), 1.96 (1.77–2.18), 2.26 (2.00–2.54), 2.60 (2.11–3.21), and 3.01 (2.06–4.39), respectively. The summary RR was 0.76 (95% CI: 0.63–0.93, I 2 = 54%, n = 5) for high vs. low physical activity and 0.74 (95% CI: 0.57–0.97, I 2 = 39.5%, p heterogeneity = 0.20, n = 2) for high vs. low vigorous physical activity. Conclusions These results suggest that even moderate increases in BMI may increase the risk of diverticular disease as well as diverticular disease complications and that a higher level of physical activity may reduce the risk. Electronic supplementary material The online version of this article (doi:10.1007/s00394-017-1443-x) contains supplementary material, which is available to authorized users.

Use of dietary supplements is rising in countries where colorectal cancer is prevalent. We conducted a systematic literature review and meta-analyses of prospective cohort studies on dietary supplement use and colorectal cancer risk. We identified relevant studies in Medline, Embase and Cochrane up to January 2013. Original and peer-reviewed papers on dietary supplement use and colorectal cancer, colon cancer, or rectal cancer incidence were included. "Use-no use"(U-NU), "highest-lowest"(H-L) and "dose-response"(DR) meta-analyses were performed. Random-effects models were used to estimate summary estimates. In total, 24 papers were included in the meta-analyses. We observed inverse associations for colorectal cancer risk and multivitamin (U-NU: RR = 0.92; 95% CI: 0.87,0.97) and calcium supplements (U-NU: RR = 0.86; 95% CI: 0.79,0.95; H-L: RR = 0.80; 95% CI: 0.70,0.92; DR: for an increase of 100 mg/day, RR = 0.96; 95% CI: 0.94,0.99). Inconsistent associations were found for colon cancer risk and supplemental vitamin A and vitamin C, and for colorectal cancer risk and supplemental vitamin D, vitamin E, garlic and folic acid. Meta-analyses of observational studies suggest a beneficial role for multivitamins and calcium supplements on colorectal cancer risk, while the association with other supplements and colorectal cancer risk is inconsistent. Residual confounding of lifestyle factors might be present. Before recommendations can be made, an extensive assessment of dietary supplement use and a better understanding of underlying mechanisms is needed.

In the World Cancer Research Fund/American Institute for Cancer Research report from 2007 the evidence relating body fatness to ovarian cancer risk was considered inconclusive, while the evidence supported a probably causal relationship between adult attained height and increased risk. Several additional cohort studies have since been published, and therefore we conducted an updated meta-analysis of the evidence as part of the Continuous Update Project. We searched PubMed and several other databases up to December 2013. Summary relative risks (RRs) were calculated using a random effects model. The summary relative risk for a 5 unit increment in BMI was 1.07 (95% CI: 1.02-1.11, I2=53%, n=26 studies). There was evidence of a nonlinear association, pnonlinearity

Greater body fatness has been associated with increased risk of gout in several studies; however, the strength of the association has differed between studies, and it is not clear whether the association differs by gender. We conducted a systematic review and meta-analysis of prospective studies to clarify the association between adiposity and risk of gout. PubMed and Embase were searched up to August 30, 2013. Summary relative risks (RRs) were calculated using a random effects model. Ten prospective studies of body mass index (BMI) and gout risk with 27,944 cases and 215,739 participants were included (median follow-up 10.5 years). The summary RR for a 5 unit increment was 1.55 [95 % confidence interval (95 % CI) 1.44–1.66, I 2 = 67 %] for all studies combined. The heterogeneity was explained by one study, which appeared to be an outlier. The summary RR per 5 BMI units was 1.62 (95 % CI 1.33–1.98, I 2 = 79 %) for men and 1.49 (95 % CI 1.32–1.68, I 2 = 30 %) for women, p heterogeneity = 0.72. The relative risks were 1.78, 2.67, 3.62, and 4.64 for persons with BMI 25, 30, 35, and 40 compared with persons with a BMI of 20. BMI in young adulthood, waist-to-hip ratio, and weight gain from age 21–25 to midlife were also associated with increased risk, but few studies were included in these analyses. Greater body mass index increases risk of gout. Further studies are needed on adiposity throughout the life course, waist-to-hip ratio, and weight changes in relation to gout as there were few studies that had published on these exposures.

Background: We conducted a systematic review and meta-analysis of existing data from observational studies to assess the strength of the association of alcohol drinking with second primary cancer risk in patients with upper aerodigestive tract (UADT; oral cavity, pharynx, larynx, and esophagus) cancer. Methods: PubMed and Embase were searched up to July 2012 and the reference lists of studies included in the analysis were examined. Random-effects models were used to estimate summary relative risks (RR) and 95% confidence interval (CI). Results: Nineteen studies, 8 cohort and 11 case–control studies, were included. In highest versus lowest meta-analyses, alcohol drinking was associated with significantly increased risk of UADT second primary cancers (RR, 2.97; 95% CI, 1.96–4.50). Significantly increased risks were also observed for UADT and lung combined (RR, 1.90; 95% CI, 1.16–3.11) and all sites (RR, 1.60; 95% CI, 1.22–2.10) second primary cancers. For an increase in the alcohol intake of 10 grams per day, dose–response meta-analysis resulted in a significantly increased RR of 1.09 (95% CI, 1.04–1.14) for UADT second primary cancers. Conclusions: Alcohol drinking in patients with UADT cancer is associated with an increased risk of second primary cancers. Studies conducted in alcohol drinking patients with UADT cancer and evaluating the effect of alcohol cessation on second primary cancer and other outcomes are needed. Impact: Our results emphasize the importance of prevention policies aiming to reduce alcohol drinking. Health-care professionals should encourage alcohol drinking patients with UADT cancer to reduce their consumption and reinforce the surveillance of this at-risk subpopulation. Cancer Epidemiol Biomarkers Prev; 23(2); 324–31. ©2013 AACR.

Current evidence indicates that red and processed meat intake increases the risk of colorectal cancer; however, the association with colorectal adenomas is unclear. To conduct a systematic review and meta-analysis of epidemiological studies of red and processed meat intake and risk of colorectal adenomas as part of the Continuous Update Project of the World Cancer Research Fund. PubMed and several other databases were searched for relevant studies from their inception up to 31 December 2011. Summary relative risks (RRs) were estimated using a random effects model. Nineteen case–control studies and seven prospective studies were included in the analyses. The summary RR per 100 g/day of red meat was 1.27 (95 % CI 1.16–1.40, I 2 = 5 %, n = 16) for all studies combined, 1.20 (95 % CI 1.06–1.36, I 2 = 0 %, n = 6) for prospective studies, and 1.34 (95 % CI 1.12–1.59, I 2 = 31 %, n = 10) for case–control studies. The summary RR per 50 g/day of processed meat intake was 1.29 (95 % CI 1.10–1.53, I 2 = 27 %, n = 10) for all studies combined, 1.45 (95 % CI 1.10–1.90, I 2 = 0 %, n = 2) for prospective studies, and 1.23 (95 % CI 0.99–1.52, I 2 = 37 %, n = 8) for case–control studies. There was evidence of a nonlinear association between red meat (p nonlinearity

Background: Fatty acids in blood may be related to the risk of prostate cancer, but epidemiologic evidence is inconsistent. Blood fatty acids are correlated through shared food sources and common endogenous desaturation and elongation pathways. Studies of individual fatty acids cannot take this into account, but pattern analysis can. Treelet transform (TT) is a novel method that uses data correlation structures to derive sparse factors that explain variation. Objective: The objective was to gain further insight in the association between plasma fatty acids and risk of prostate cancer by applying TT to take data correlations into account. Design: We reanalyzed previously published data from a case-control study of prostate cancer nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. TT was used to derive factors explaining the variation in 26 plasma phospholipid fatty acids of 962 incident prostate cancer cases matched to 1061 controls. Multiple imputation was used to deal with missing data in covariates. ORs of prostate cancer according to factor scores were determined by using multivariable conditional logistic regression. Results: Four simple factors explained 38% of the variation in plasma fatty acids. A high score on a factor reflecting a long-chain n-3 PUFA pattern was associated with greater risk of prostate cancer (OR for highest compared with lowest quintile: 1.36; 95% CI: 0.99, 1.86; P-trend = 0.041). Conclusion: Pattern analyses using TT groupings of correlated fatty acids indicate that intake or metabolism of long-chain n-3 PUFAs may be relevant to prostate cancer etiology. Am J Clin Nutr 2012;96:1354-61.

Pancreatic cancer is the fourth most common cause of cancer death worldwide with large geographical variation, which implies the contribution of diet and lifestyle in its etiology. We examined the association of meat and fish consumption with risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 477,202 EPIC participants from 10 European countries recruited between 1992 and 2000 were included in our analysis. Until 2008, 865 nonendocrine pancreatic cancer cases have been observed. Calibrated relative risks (RRs) and 95% confidence intervals (CIs) were computed using multivariable-adjusted Cox hazard regression models. The consumption of red meat (RR per 50 g increase per day = 1.03, 95% CI = 0.93-1.14) and processed meat (RR per 50 g increase per day = 0.93, 95% CI = 0.71-1.23) were not associated with an increased pancreatic cancer risk. Poultry consumption tended to be associated with an increased pancreatic cancer risk (RR per 50 g increase per day = 1.72, 95% CI = 1.04-2.84); however, there was no association with fish consumption (RR per 50 g increase per day = 1.22, 95% CI = 0.92-1.62). Our results do not support the conclusion of the World Cancer Research Fund that red or processed meat consumption may possibly increase the risk of pancreatic cancer. The positive association of poultry consumption with pancreatic cancer might be a chance finding as it contradicts most previous findings.

PURPOSE: Data from prospective epidemiological studies in Asian populations and from experimental studies in animals and cell lines suggest a possible protective association between dietary isoflavones and the development of prostate cancer. We examined the association between circulating concentrations of genistein and prostate cancer risk in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition. METHODS: Concentrations of the isoflavone genistein were measured in prediagnostic plasma samples for 1,605 prostate cancer cases and 1,697 matched control participants. Relative risks (RRs) for prostate cancer in relation to plasma concentrations of genistein were estimated by conditional logistic regression. RESULTS: Plasma genistein concentrations were not associated with prostate cancer risk; the multivariate relative risk for men in the highest fifth of genistein compared with men in the lowest fifth was 1.00 (95 % confidence interval: 0.79, 1.27; p linear trend = 0.82). There was no evidence of heterogeneity in this association by age at blood collection, country of recruitment, or cancer stage or histological grade. CONCLUSION: Plasma genistein concentration was not associated with prostate cancer risk in this large cohort of European men.

Obesity, a major risk factor for endometrial cancer, is a low-grade inflammatory state characterized by elevated concentrations of cytokines and acute phase reactants. The current study had two aims: first to investigate the associations of C-reactive protein (CRP), interleukin 6 (IL6), and IL1 receptor antagonist (IL1Ra) with endometrial cancer risk and second to examine to which extent these markers can influence the association between obesity and endometrial cancer. We conducted a case–control study, nested within the European Prospective Investigation into Cancer and Nutrition, which comprised 305 incident cases of endometrial cancer and 574 matched controls. CRP, IL6, and IL1Ra were measured in prospectively collected blood specimens by immunoassays. Data were analyzed using conditional logistic regression. All statistical tests were two-sided, and P values Ptrend=0.02), IL6 (OR for top versus bottom quartile: 1.66, 95% CI: 1.08–2.54, Ptrend=0.008), and IL1Ra (OR for top versus bottom quartile: 1.82, 95% CI: 1.22–2.73, Ptrend=0.004). After adjustment for body mass index (BMI), the estimates were strongly reduced and became non-significant. The association between BMI and endometrial cancer was also substantially attenuated (∼10–20%) after adjustment for inflammatory markers, even when the effects of C-peptide or estrone had already been taken into account. We provided epidemiological evidence that chronic inflammation might mediate the association between obesity and endometrial cancer and that endometrial carcinogenesis could be promoted by an inflammatory milieu.

Objective To quantify the dose-response relation between consumption of whole grain and specific types of grains and the risk of cardiovascular disease, total cancer, and all cause and cause specific mortality. Data sources PubMed and Embase searched up to 3 April 2016. Study selection Prospective studies reporting adjusted relative risk estimates for the association between intake of whole grains or specific types of grains and cardiovascular disease, total cancer, all cause or cause specific mortality. Data synthesis Summary relative risks and 95% confidence intervals calculated with a random effects model. Results 45 studies (64 publications) were included. The summary relative risks per 90 g/day increase in whole grain intake (90 g is equivalent to three servings—for example, two slices of bread and one bowl of cereal or one and a half pieces of pita bread made from whole grains) was 0.81 (95% confidence interval 0.75 to 0.87; I 2 =9%, n=7 studies) for coronary heart disease, 0.88 (0.75 to 1.03; I 2 =56%, n=6) for stroke, and 0.78 (0.73 to 0.85; I 2 =40%, n=10) for cardiovascular disease, with similar results when studies were stratified by whether the outcome was incidence or mortality. The relative risks for morality were 0.85 (0.80 to 0.91; I 2 =37%, n=6) for total cancer, 0.83 (0.77 to 0.90; I 2 =83%, n=11) for all causes, 0.78 (0.70 to 0.87; I 2 =0%, n=4) for respiratory disease, 0.49 (0.23 to 1.05; I 2 =85%, n=4) for diabetes, 0.74 (0.56 to 0.96; I 2 =0%, n=3) for infectious diseases, 1.15 (0.66 to 2.02; I 2 =79%, n=2) for diseases of the nervous system disease, and 0.78 (0.75 to 0.82; I 2 =0%, n=5) for all non-cardiovascular, non-cancer causes. Reductions in risk were observed up to an intake of 210-225 g/day (seven to seven and a half servings per day) for most of the outcomes. Intakes of specific types of whole grains including whole grain bread, whole grain breakfast cereals, and added bran, as well as total bread and total breakfast cereals were also associated with reduced risks of cardiovascular disease and/or all cause mortality, but there was little evidence of an association with refined grains, white rice, total rice, or total grains. Conclusions This meta-analysis provides further evidence that whole grain intake is associated with a reduced risk of coronary heart disease, cardiovascular disease, and total cancer, and mortality from all causes, respiratory diseases, infectious diseases, diabetes, and all non-cardiovascular, non-cancer causes. These findings support dietary guidelines that recommend increased intake of whole grain to reduce the risk of chronic diseases and premature mortality.

Aim This systematic review and meta-analysis aimed to clarify whether tobacco smoking is associated with an increased risk of diverticular disease. Methods PubMed and Embase databases were searched for studies of smoking and diverticular disease up to February 19, 2016. Prospective studies that reported adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) of diverticular disease associated with current, r or previous smoking were included. Summary RRs were estimated using a random effects model. Results We identified five prospective studies which comprised 6,076 incident diverticular disease (diverticulosis and diverticulitis) cases, 385,291 participants and three studies with 1,118 cases of complications related to diverticular disease (abscess or perforation) among 292,965 participants that could be included in the meta-analysis. The summary RR for incident diverticular disease was 1.36 (95% CI: 1.15-1.61, I2=84%, n=4) for current smokers, 1.17 (95% CI: 1.05-1.31, I2=49%, n=4) for former smokers and 1.33 (95% CI: 1.22-1.46, I2=55%, n=7) for ever smokers. The summary relative risk was 1.11 (95% CI: 0.99-1.25,I2=82%, n=4) per 10 cigarettes per day. Although there was some indication of nonlinearity there was a dose-dependent positive association with increasing number of cigarettes smoked per day. There was some evidence that smoking also increases the risk of diverticular disease complications, but the number of studies was small. Conclusion The current meta-analysis provides evidence that tobacco smoking is associated with an increased incidence of of diverticular disease and related complications. This article is protected by copyright. All rights reserved.

Prevention of hip fractures is of critical public health importance. In a cohort of adults from eight European countries, evidence was found that increased adherence to Mediterranean diet, measured by a 10-unit dietary score, is associated with reduced hip fracture incidence, particularly among men. Evidence on the role of dietary patterns on hip fracture incidence is scarce. We explored the association of adherence to Mediterranean diet (MD) with hip fracture incidence in a cohort from eight European countries. A total of 188,795 eligible participants (48,814 men and 139,981 women) in the European Prospective Investigation into Cancer and nutrition study with mean age 48.6 years (±10.8) were followed for a median of 9 years, and 802 incident hip fractures were recorded. Diet was assessed at baseline through validated dietary instruments. Adherence to MD was evaluated by a MD score (MDs), on a 10-point scale, in which monounsaturated were substituted with unsaturated lipids. Association with hip fracture incidence was assessed through Cox regression with adjustment for potential confounders. Increased adherence to MD was associated with a 7 % decrease in hip fracture incidence [hazard ratio (HR) per 1-unit increase in the MDs 0.93; 95 % confidence interval (95 % CI) = 0.89–0.98]. This association was more evident among men and somewhat stronger among older individuals. Using increments close to one standard deviation of daily intake, in the overall sample, high vegetable (HR = 0.86; 95 % CI = 0.79–0.94) and high fruit (HR = 0.89; 95 % CI = 0.82–0.97) intake was associated with decreased hip fracture incidence, whereas high meat intake (HR = 1.18; 95 % CI = 1.06–1.31) with increased incidence. Excessive ethanol consumption (HR high versus moderate = 1.74; 95 % CI = 1.32–2.31) was also a risk factor. In a prospective study of adults, increased adherence to MD appears to protect against hip fracture occurrence, particularly among men.

BACKGROUND: The glycemic potential of a diet is associated with chronically elevated insulin concentrations, which may augment breast cancer (BC) risk by stimulating insulin receptor or by affecting insulin-like growth factor I (IGF-I)-mediated mitogenesis. It is unclear whether this effect differs by BC phenotype. OBJECTIVE: The objective was to investigate the relation between glycemic index (GI), glycemic load (GL), and total carbohydrate intake with BC by using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN: We identified 11,576 women with invasive BC among 334,849 EPIC women aged 34-66 y (5th to 95th percentiles) at baseline over a median follow-up of 11.5 y. Dietary GI and GL were calculated from country-specific dietary questionnaires. We used multivariable Cox proportional hazards models to quantify the association between GI, GL, and carbohydrate intake and BC risk. BC tumors were classified by receptor status. RESULTS: Overall GI, GL, and carbohydrates were not related to BC. Among postmenopausal women, GL and carbohydate intake were significantly associated with an increased risk of estrogen receptor-negative (ER(-)) BC when extreme quintiles (Q) were compared [multivariable HR(Q5-Q1) (95% CI) = 1.36 (1.02, 1.82; P-trend = 0.010) and HR(Q5-Q1) = 1.41 (1.05, 1.89; P-trend = 0.009), respectively]. Further stratification by progesterone receptor (PR) status showed slightly stronger associations with ER(-)/PR(-) BC [HR(Q5-Q1) (95% CI) = 1.48 (1.07, 2.05; P-trend = 0.010) for GL and HR(Q5-Q1) = 1.62 (1.15, 2.30; P-trend = 0.005) for carbohydrates]. No significant association with ER-positive BC was observed. CONCLUSION: Our results indicate that a diet with a high GL and carbohydrate intake is positively associated with an increased risk of developing ER(-) and ER(-)/PR(-) BC among postmenopausal women.

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, I2 = 0%] for dietary fiber, 0.95 (95% CI 0.86–1.06, I2 = 4%) for fruit fiber, 0.99 (95% CI 0.92–1.07, I2 = 1%) for vegetable fiber, 0.96 (95% CI 0.90–1.02, I2 = 5%) for cereal fiber, 0.91 (95% CI 0.84–0.99, I2 = 7%) for soluble fiber and 0.95 (95% CI 0.89–1.02, I2 = 0%) for insoluble fiber. The summary RR per 10 g/day of dietary fiber was 0.95 (95% CI 0.91–0.98, I2 = 0%, Pheterogeneity = 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.

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.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.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%).Both general and abdominal fatness increases pancreatic cancer risk. Among nonsmokers, risk increases even among persons within the normal BMI range.

Dietary carbohydrate, glycemic index, and glycemic load are thought to influence colorectal cancer risk through hyperinsulinemia. We review and quantitatively summarize in a meta-analysis the evidence from prospective cohort studies. We searched the PubMed database for prospective studies of carbohydrate, glycemic index, and glycemic load and colorectal cancer risk, up to October 2011. Summary relative risks were estimated by the use of a random effects model. We identified 14 cohort studies that could be included in the meta-analysis of carbohydrate, glycemic index, and glycemic load and colorectal cancer risk. The summary RR for high versus low intake was 1.00 (95% CI: 0.87–1.14, I 2 = 31%) for carbohydrate, 1.07 (95% CI: 0.99–1.16, I 2 = 28%) for glycemic index, and 1.00 (95% CI: 0.91–1.10, I 2 = 39%) for glycemic load. In the dose–response analysis, the summary RR was 0.95 (95% CI: 0.84–1.07, I 2 = 58%) per 100 grams of carbohydrate per day, 1.07 (95% CI: 0.99–1.15, I 2 = 39%) per 10 glycemic index units, and 1.01 (95% CI: 0.95–1.08, I 2 = 47%) per 50 glycemic load units. Exclusion of one or two outlying studies reduced the heterogeneity, but the results were similar. This meta-analysis of cohort studies does not support an independent association between diets high in carbohydrate, glycemic index, or glycemic load and colorectal cancer risk.