Postdiagnosis body fatness, recreational physical activity, dietary factors and breast cancer prognosis: Global Cancer Update Programme (CUP Global) summary of evidence grading.

Based on the Global Cancer Update Programme, formally known as the World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project, we performed systematic reviews and meta-analyses to investigate the association of postdiagnosis body fatness, physical activity and dietary factors with breast cancer prognosis. We searched PubMed and Embase for randomised controlled trials and longitudinal observational studies from inception to 31 October 2021. We calculated summary relative risks (RRs) and 95% confidence intervals (CIs) using random-effects meta-analyses. An independent Expert Panel graded the quality of evidence according to predefined criteria. The evidence on postdiagnosis body fatness and higher all-cause mortality (RR per 5 kg/m2 in body mass index: 1.07, 95% CI: 1.05-1.10), breast cancer-specific mortality (RR: 1.10, 95% CI: 1.06-1.14) and second primary breast cancer (RR: 1.14, 95% CI: 1.04-1.26) was graded as strong (likelihood of causality: probable). The evidence for body fatness and breast cancer recurrence and other nonbreast cancer-related mortality was graded as limited (likelihood of causality: limited-suggestive). The evidence on recreational physical activity and lower risk of all-cause (RR per 10 metabolic equivalent of task-hour/week: 0.85, 95% CI: 0.78-0.92) and breast cancer-specific mortality (RR: 0.86, 95% CI: 0.77-0.96) was judged as limited-suggestive. Data on dietary factors was limited, and no conclusions could be reached except for healthy dietary patterns, isoflavone and dietary fibre intake and serum 25(OH)D concentrations that were graded with limited-suggestive evidence for lower risk of the examined outcomes. Our results encourage the development of lifestyle recommendations for breast cancer patients to avoid obesity and be physically active.

Postdiagnosis body fatness, weight change and breast cancer prognosis: Global Cancer Update Program (CUP global) systematic literature review and meta-analysis.

Previous evidence on postdiagnosis body fatness and mortality after breast cancer was graded as limited-suggestive. To evaluate the evidence on body mass index (BMI), waist circumference, waist-hip-ratio and weight change in relation to breast cancer prognosis, an updated systematic review was conducted. PubMed and Embase were searched for relevant studies published up to 31 October, 2021. Random-effects meta-analyses were conducted to estimate summary relative risks (RRs). The evidence was judged by an independent Expert Panel using pre-defined grading criteria. One randomized controlled trial and 225 observational studies were reviewed (220 publications). There was strong evidence (likelihood of causality: probable) that higher postdiagnosis BMI was associated with increased all-cause mortality (64 studies, 32 507 deaths), breast cancer-specific mortality (39 studies, 14 106 deaths) and second primary breast cancer (11 studies, 5248 events). The respective summary RRs and 95% confidence intervals per 5 kg/m2 BMI were 1.07 (1.05-1.10), 1.10 (1.06-1.14) and 1.14 (1.04-1.26), with high between-study heterogeneity (I2  = 56%, 60%, 66%), but generally consistent positive associations. Positive associations were also observed for waist circumference, waist-hip-ratio and all-cause and breast cancer-specific mortality. There was limited-suggestive evidence that postdiagnosis BMI was associated with higher risk of recurrence, nonbreast cancer deaths and cardiovascular deaths. The evidence for postdiagnosis (unexplained) weight or BMI change and all outcomes was graded as limited-no conclusion. The RCT showed potential beneficial effect of intentional weight loss on disease-free-survival, but more intervention trials and well-designed observational studies in diverse populations are needed to elucidate the impact of body composition and their changes on breast cancer outcomes.

Postdiagnosis recreational physical activity and breast cancer prognosis: Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis.

It is important to clarify the associations between modifiable lifestyle factors such as physical activity and breast cancer prognosis to enable the development of evidence-based survivorship recommendations. We performed a systematic review and meta-analyses to summarise the evidence on the relationship between postbreast cancer diagnosis physical activity and mortality, recurrence and second primary cancers. We searched PubMed and Embase through 31st October 2021 and included 20 observational studies and three follow-up observational analyses of patients enrolled in clinical trials. In linear dose-response meta-analysis of the observational studies, each 10-unit increase in metabolic equivalent of task (MET)-h/week higher recreational physical activity was associated with 15% and 14% lower risk of all-cause (95% confidence interval [CI]: 8%-22%, studies = 12, deaths = 3670) and breast cancer-specific mortality (95% CI: 4%-23%, studies = 11, deaths = 1632), respectively. Recreational physical activity was not associated with breast cancer recurrence (HR = 0.97, 95% CI: 0.91-1.05, studies = 6, deaths = 1705). Nonlinear dose-response meta-analyses indicated 48% lower all-cause and 38% lower breast cancer-specific mortality with increasing recreational physical activity up to 20 MET-h/week, but little further reduction in risk at higher levels. Predefined subgroup analyses across strata of body mass index, hormone receptors, adjustment for confounders, number of deaths, menopause and physical activity intensities were consistent in direction and magnitude to the main analyses. Considering the methodological limitations of the included studies, the independent Expert Panel concluded 'limited-suggestive' likelihood of causality for an association between recreational physical activity and lower risk of all-cause and breast cancer-specific mortality.

Postdiagnosis dietary factors, supplement use and breast cancer prognosis: Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis.

Little is known about how diet might influence breast cancer prognosis. The current systematic reviews and meta-analyses summarise the evidence on postdiagnosis dietary factors and breast cancer outcomes from randomised controlled trials and longitudinal observational studies. PubMed and Embase were searched through 31st October 2021. Random-effects linear dose-response meta-analysis was conducted when at least three studies with sufficient information were available. The quality of the evidence was evaluated by an independent Expert Panel. We identified 108 publications. No meta-analysis was conducted for dietary patterns, vegetables, wholegrains, fish, meat, and supplements due to few studies, often with insufficient data. Meta-analysis was only possible for all-cause mortality with dairy, isoflavone, carbohydrate, dietary fibre, alcohol intake and serum 25-hydroxyvitamin D (25(OH)D), and for breast cancer-specific mortality with fruit, dairy, carbohydrate, protein, dietary fat, fibre, alcohol intake and serum 25(OH)D. The results, with few exceptions, were generally null. There was limited-suggestive evidence that predefined dietary patterns may reduce the risk of all-cause and other causes of death; that isoflavone intake reduces the risk of all-cause mortality (relative risk (RR) per 2 mg/day: 0.96, 95% confidence interval (CI): 0.92-1.02), breast cancer-specific mortality (RR for high vs low: 0.83, 95% CI: 0.64-1.07), and recurrence (RR for high vs low: 0.75, 95% CI: 0.61-0.92); that dietary fibre intake decreases all-cause mortality (RR per 10 g/day: 0.87, 95% CI: 0.80-0.94); and that serum 25(OH)D is inversely associated with all-cause and breast cancer-specific mortality (RR per 10 nmol/L: 0.93, 95% CI: 0.89-0.97 and 0.94, 95% CI: 0.90-0.99, respectively). The remaining associations were graded as limited-no conclusion.

Physical Activity and Health-Related Quality of Life in Women With Breast Cancer: A Meta-Analysis.

BACKGROUND: Physical activity (PA) is associated with improved health-related quality of life (HRQoL) among women with breast cancer; however, uncertainty remains regarding PA types and dose (frequency, duration, intensity) and various HRQoL measures. A systematic review and meta-analysis of randomized controlled trials was conducted to clarify whether specific types and doses of physical activity was related to global and specific domains of HRQoL, as part of the Global Cancer Update Programme, formerly known as the World Cancer Research Fund-American Institute for Cancer Research Continuous Update Project. METHODS: PubMed and CENTRAL databases were searched up to August 31, 2019. Weighted mean differences (WMDs) in HRQoL scores were estimated using random effects models. An independent expert panel graded the evidence. RESULTS: A total of 79 randomized controlled trials (14 554 breast cancer patients) were included. PA interventions resulted in higher global HRQoL as measured by the Functional Assessment of Cancer Therapy-Breast (WMD = 5.94, 95% confidence intervals [CI] = 2.64 to 9.24; I2 = 59%, n = 12), Functional Assessment of Cancer Therapy-General (WMD = 4.53, 95% CI = 1.94 to 7.13; I2 = 72%, n = 18), and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (WMD = 6.78, 95% CI = 2.61 to 10.95; I2 = 76.3%, n = 17). The likelihood of causality was considered probable that PA improves HRQoL in breast cancer survivors. Effects were weaker for physical function and mental and emotional health. Evidence regarding dose and type of PA remains insufficient for firm conclusions. CONCLUSION: PA results in improved global HRQoL in breast cancer survivors with weaker effects observed for physical function and mental and emotional health. Additional research is needed to define the impact of types and doses of activity on various domains of HRQoL.

Primary sclerosing cholangitis and the risk of cancer, cardiovascular disease, and all-cause mortality: a systematic review and meta-analysis of cohort studies.

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.

High Body Mass Index and Central Adiposity Is Associated with Increased Risk of Acute Pancreatitis: A Meta-Analysis.

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 < 0.0001, with a steeper association at higher levels of BMI, but not for waist circumference, pnonlinearity = 0.19. Comparing a BMI of 35 with a BMI of 22, there was a 58% increase in the RR and there was a fourfold increase in the RR comparing a waist circumference of 110 cm with 69 cm. There was no evidence of publication bias. CONCLUSIONS: This meta-analysis suggests that both increasing BMI and waist circumference are associated with a dose-response-related increase in the risk of acute pancreatitis.

Physical activity and the risk of heart failure: a systematic review and dose-response meta-analysis of prospective studies.

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.

Physical activity and the risk of abdominal aortic aneurysm: a systematic review and meta-analysis of prospective studies.

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.

Physical activity and the risk of sudden cardiac death: a systematic review and meta-analysis of prospective studies.

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.

Diabetes mellitus and the risk of pancreatitis: A systematic review and meta-analysis of cohort studies.

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.

Dietary fibre intake and the risk of diverticular disease: a systematic review and meta-analysis of prospective studies.

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.

Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort.

BACKGROUND & AIMS: There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. RESULTS: Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80-0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82-0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83-1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78-0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18-1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026). CONCLUSIONS: In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.

Tobacco smoking and the risk of pancreatitis: A systematic review and meta-analysis of prospective studies.

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.

World Cancer Research Fund International: Continuous Update Project-systematic literature review and meta-analysis of observational cohort studies on physical activity, sedentary behavior, adiposity, and weight change and breast cancer 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.

Role of diet in type 2 diabetes incidence: umbrella review of meta-analyses of prospective observational studies.

OBJECTIVE: To summarise the evidence of associations between dietary factors and incidence of type 2 diabetes and to evaluate the strength and validity of these associations. DESIGN: Umbrella review of systematic reviews with meta-analyses of prospective observational studies. DATA SOURCES: PubMed, Web of Science, and Embase, searched up to August 2018. ELIGIBILITY CRITERIA: Systematic reviews with meta-analyses reporting summary risk estimates for the associations between incidence of type 2 diabetes and dietary behaviours or diet quality indices, food groups, foods, beverages, alcoholic beverages, macronutrients, and micronutrients. RESULTS: 53 publications were included, with 153 adjusted summary hazard ratios on dietary behaviours or diet quality indices (n=12), food groups and foods (n=56), beverages (n=10), alcoholic beverages (n=12), macronutrients (n=32), and micronutrients (n=31), regarding incidence of type 2 diabetes. Methodological quality was high for 75% (n=115) of meta-analyses, moderate for 23% (n=35), and low for 2% (n=3). Quality of evidence was rated high for an inverse association for type 2 diabetes incidence with increased intake of whole grains (for an increment of 30 g/day, adjusted summary hazard ratio 0.87 (95% confidence interval 0.82 to 0.93)) and cereal fibre (for an increment of 10 g/day, 0.75 (0.65 to 0.86)), as well as for moderate intake of total alcohol (for an intake of 12-24 g/day v no consumption, 0.75 (0.67 to 0.83)). Quality of evidence was also high for the association for increased incidence of type 2 diabetes with higher intake of red meat (for an increment of 100 g/day, 1.17 (1.08 to 1.26)), processed meat (for an increment of 50 g/day, 1.37 (1.22 to 1.54)), bacon (per two slices/day, 2.07 (1.40 to 3.05)), and sugar sweetened beverages (for an increase of one serving/day, 1.26 (1.11 to 1.43)). CONCLUSIONS: Overall, the association between dietary factors and type 2 diabetes has been extensively studied, but few of the associations were graded as high quality of evidence. Further factors are likely to be important in type 2 diabetes prevention; thus, more well conducted research, with more detailed assessment of diet, is needed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018088106.

Dietary patterns derived from principal component analysis (PCA) and risk of colorectal cancer: a systematic review and meta-analysis.

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 the 31st July 2017. Any pre-defined cancer of 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.

Tobacco smoking and the risk of heart failure: A systematic review and meta-analysis of prospective studies.

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.

Dietary intake and blood concentrations of antioxidants and the risk of cardiovascular disease, total cancer, and all-cause mortality: a systematic review and dose-response meta-analysis of prospective studies.

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, ß-carotene, α-carotene, ß-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.