A systematic review and meta-analysis of the 2007 WCRF/AICR score in relation to cancer-related health outcomes.

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.

Body mass index, abdominal fatness, weight gain and the risk of urinary incontinence: a systematic review and dose-response meta-analysis of prospective studies.

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.

Body size and obesity during adulthood, and risk of lympho-haematopoietic cancers: an update of the WCRF-AICR systematic review of published prospective studies.

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

Diabetes mellitus, blood glucose and the risk of heart failure: A systematic review and meta-analysis of prospective studies.

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%, pheterogeneity<0.0001) for diabetes vs. no diabetes (n = 41, 100284 cases and >613925 participants) and 1.25 (95% CI: 0.89-1.75, I2 = 95.6%, pheterogeneity<0.0001) per 20 mg/dl increase in blood glucose (1016 cases, 34309 participants, n = 2). In the analyses of diabetes and heart failure there was low or no heterogeneity among the population-based studies that adjusted for alcohol intake and physical activity and among the patient-based studies there was no heterogeneity among studies with ≥10 years follow-up. CONCLUSIONS: These results suggest that individuals with diabetes are at an increased risk of developing heart failure and there is evidence of increased risk even within the pre-diabetic range of blood glucose.

Diabetes mellitus and the risk of sudden cardiac death: A systematic review and meta-analysis of prospective studies.

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.

An update of the WCRF/AICR systematic literature review and meta-analysis on dietary and anthropometric factors and esophageal cancer risk.

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.

Tobacco smoking and the risk of diverticular disease - a systematic review and meta-analysis of prospective studies.

AIM: This systematic review and meta-analysis aimed to clarify whether tobacco smoking is associated with an increased risk of diverticular disease. METHOD: The PubMed and Embase databases were searched for studies of smoking and diverticular disease up to 19 February 2016. Prospective studies that reported adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) of diverticular disease associated with current or previous smoking were included. Summary RRs were estimated using a random effects model. RESULTS: We identified five prospective studies which comprised 6076 cases of incident diverticular disease (diverticulosis and diverticulitis) among 385 291 participants and three studies with 1118 cases of complications related to diverticular disease (abscess or perforation) among 292 965. 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 1.29 (95% CI 1.16-1.44, I2  = 62%, n = 5) for ever smokers. The summary RR 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 complications of diverticular disease, but the number of studies was small. CONCLUSION: The current meta-analysis provides evidence that tobacco smoking is associated with an increased incidence of diverticular disease and related complications.

Foods and beverages and colorectal cancer risk: a systematic review and meta-analysis of cohort studies, an update of the evidence of the WCRF-AICR Continuous Update Project.

OBJECTIVE: As part of the World Cancer Research Fund International Continuous Update Project, we updated the systematic review and meta-analysis of prospective studies to quantify the dose-response between foods and beverages intake and colorectal cancer risk. DATA SOURCES: PubMed and several databases up to 31 May 2015. STUDY SELECTION: Prospective studies reporting adjusted relative risk estimates for the association of specific food groups and beverages and risk of colorectal, colon and rectal cancer. DATA SYNTHESIS: Dose-response meta-analyses using random effect models to estimate summary relative risks (RRs). RESULTS: About 400 individual study estimates from 111 unique cohort studies were included. Overall, the risk increase of colorectal cancer is 12% for each 100 g/day increase of red and processed meat intake (95% CI = 4-21%, I2=70%, pheterogeneity (ph)<0.01) and 7% for 10 g/day increase of ethanol intake in alcoholic drinks (95% CI = 5-9%, I2=25%, ph = 0.21). Colorectal cancer risk decrease in 17% for each 90g/day increase of whole grains (95% CI = 11-21%, I2 = 0%, ph = 0.30, 6 studies) and 13% for each 400 g/day increase of dairy products intake (95% CI = 10-17%, I2 = 18%, ph = 0.27, 10 studies). Inverse associations were also observed for vegetables intake (RR per 100 g/day =0.98 (95% CI = 0.96-0.99, I2=0%, ph = 0.48, 11 studies) and for fish intake (RR for 100 g/day = 0.89 (95% CI = 0.80-0.99, I2=0%, ph = 0.52, 11 studies), that were weak for vegetables and driven by one study for fish. Intakes of fruits, coffee, tea, cheese, poultry and legumes were not associated with colorectal cancer risk. CONCLUSIONS: Our results reinforce the evidence that high intake of red and processed meat and alcohol increase the risk of colorectal cancer. Milk and whole grains may have a protective role against colorectal cancer. The evidence for vegetables and fish was less convincing.

Adult weight gain and colorectal adenomas-a systematic review and meta-analysis.

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

Fruits, vegetables and lung cancer risk: a systematic review and meta-analysis.

BACKGROUND: Lung cancer is the most common cause of cancer death. Fruits and vegetables containing carotenoids and other antioxidants have been hypothesized to decrease lung cancer risk. As part of the World Cancer Research Fund International Continuous Update Project, we conducted a systematic review and meta-analysis of prospective studies. METHODS: We searched PubMed and several databases up to December 2014 for prospective studies. We conducted meta-analyses comparing the highest and lowest intakes and dose-response meta-analyses to estimate summary relative risks (RRs) and 95% confidence intervals (CIs), and examine possible non-linear associations. We combined results from the Pooling Project with the studies we identified to increase the statistical power of our analysis. RESULTS: When comparing the highest with the lowest intakes, the summary RR estimates were 0.86 [95% CI 0.78-0.94; n (studies) = 18] for fruits and vegetables, 0.92 (95% CI 0.87-0.97; n = 25) for vegetables and 0.82 (95% CI 0.76-0.89; n = 29) for fruits. The association with fruit and vegetable intake was marginally significant in current smokers and inverse but not significant in former or never smokers. Significant inverse dose-response associations were observed for each 100 g/day increase: for fruits and vegetables [RR: 0.96; 95% CI 0.94-0.98, I(2) = 64%, n = 14, N (cases) = 9609], vegetables (RR: 0.94; 95% CI 0.89-0.98, I(2) = 48%, n = 20, N = 12 563) and fruits (RR: 0.92; 95% CI 0.89-0.95, I(2) = 57%, n = 23, N = 14 506). Our results were consistent among the different types of fruits and vegetables. The strength of the association differed across locations. There was evidence of a non-linear relationship (P < 0.01) between fruit and vegetable intake and lung cancer risk showing that no further benefit is obtained when increasing consumption above ∼400 g per day. CONCLUSIONS: Eliminating tobacco smoking is the best strategy to prevent lung cancer. Although residual confounding by smoking cannot be ruled out, the current evidence from prospective studies is consistent with a protective role of fruit and vegetables in lung cancer aetiology.

Fruit and vegetable consumption in relation to hepatocellular carcinoma in a multi-centre, European cohort study.

BACKGROUND: Vegetable and/or fruit intakes in association with hepatocellular carcinoma (HCC) risk have been investigated in case-control studies conducted in specific European countries and cohort studies conducted in Asia, with inconclusive results. No multi-centre European cohort has investigated the indicated associations. METHODS: In 486,799 men/women from the European Prospective Investigation into Cancer and nutrition, we identified 201 HCC cases after 11 years median follow-up. We calculated adjusted hazard ratios (HRs) for HCC incidence for sex-specific quintiles and per 100 g d(-1) increments of vegetable/fruit intakes. RESULTS: Higher vegetable intake was associated with a statistically significant, monotonic reduction of HCC risk: HR (100 g d(-1) increment): 0.83; 95% CI: 0.71-0.98. This association was consistent in sensitivity analyses with no apparent heterogeneity across strata of HCC risk factors. Fruit intake was not associated with HCC incidence: HR (100 g d(-1) increment): 1.01; 95% CI: 0.92-1.11. CONCLUSIONS: Vegetable, but not fruit, intake is associated with lower HCC risk with no evidence for heterogeneity of this association in strata of important HCC risk factors. Mechanistic studies should clarify pathways underlying this association. Given that HCC prognosis is poor and that vegetables are practically universally accessible, our results may be important, especially for those at high risk for the disease.

Anthropometric factors and endometrial cancer risk: a systematic review and dose-response meta-analysis of prospective studies.

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

Body mass index and survival in women with breast cancer-systematic literature review and meta-analysis of 82 follow-up studies.

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

Breastfeeding and the maternal risk of type 2 diabetes: a systematic review and dose-response meta-analysis of cohort studies.

BACKGROUND AND AIMS: Breastfeeding has been associated with reduced risk of maternal type 2 diabetes in some cohort studies, but the evidence from published studies have differed with regard to the strength of the association. To clarify this association we conducted a systematic review and dose-response meta-analysis of breastfeeding and maternal risk of type 2 diabetes. METHODS AND RESULTS: We conducted a systematic review and dose-response meta-analysis of prospective studies of breastfeeding and maternal risk of type 2 diabetes. We searched the PubMed, Embase and Ovid databases up to September 19th 2013. Summary relative risks were estimated using a random effects model. Six cohort studies including 10,842 cases among 273,961 participants were included in the meta-analysis. The summary RR for the highest duration of breastfeeding vs. the lowest was 0.68 (95% CI: 0.57-0.82, I(2) = 75%, p heterogeneity = 0.001, n = 6). The summary RR for a three month increase in the duration of breastfeeding per child was 0.89 (95% CI: 0.77-1.04, I(2) = 93%, p heterogeneity < 0.0001, n = 3) and the summary RR for a one year increase in the total duration of breastfeeding was 0.91 (95% CI: 0.86-0.96, I(2) = 81%, p heterogeneity = 0.001, n = 4). There was little difference in the summary estimates whether or not BMI had been adjusted for. The inverse associations appeared to be nonlinear, p nonlinearity < 0.0001 for both analyses, and in both analyses the reduction in risk was steeper when increasing breastfeeding from low levels. CONCLUSION: This meta-analysis suggests that there is a statistically significant inverse association between breastfeeding and maternal risk of type 2 diabetes.

Consumption of sweet beverages and type 2 diabetes incidence in European adults: results from EPIC-InterAct.

AIMS/HYPOTHESIS: Consumption of sugar-sweetened beverages has been shown, largely in American populations, to increase type 2 diabetes incidence. We aimed to evaluate the association of consumption of sweet beverages (juices and nectars, sugar-sweetened soft drinks and artificially sweetened soft drinks) with type 2 diabetes incidence in European adults. METHODS: We established a case-cohort study including 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants selected from eight European cohorts participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. After exclusions, the final sample size included 11,684 incident cases and a subcohort of 15,374 participants. Cox proportional hazards regression models (modified for the case-cohort design) and random-effects meta-analyses were used to estimate the association between sweet beverage consumption (obtained from validated dietary questionnaires) and type 2 diabetes incidence. RESULTS: In adjusted models, one 336 g (12 oz) daily increment in sugar-sweetened and artificially sweetened soft drink consumption was associated with HRs for type 2 diabetes of 1.22 (95% CI 1.09, 1.38) and 1.52 (95% CI 1.26, 1.83), respectively. After further adjustment for energy intake and BMI, the association of sugar-sweetened soft drinks with type 2 diabetes persisted (HR 1.18, 95% CI 1.06, 1.32), but the association of artificially sweetened soft drinks became statistically not significant (HR 1.11, 95% CI 0.95, 1.31). Juice and nectar consumption was not associated with type 2 diabetes incidence. CONCLUSIONS/INTERPRETATION: This study corroborates the association between increased incidence of type 2 diabetes and high consumption of sugar-sweetened soft drinks in European adults.

Mediterranean diet and incidence of hip fractures in a European cohort.

UNLABELLED: 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. INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: In a prospective study of adults, increased adherence to MD appears to protect against hip fracture occurrence, particularly among men.

Adherence to the mediterranean diet and risk of breast cancer in the European prospective investigation into cancer and nutrition cohort study.

Epidemiological evidence suggests that the Mediterranean diet (MD) could reduce the risk of breast cancer (BC). As evidence from the prospective studies remains scarce and conflicting, we investigated the association between adherence to the MD and risk of BC among 335,062 women recruited from 1992 to 2000, in ten European countries, and followed for 11 years on average. Adherence to the MD was estimated through an adapted relative Mediterranean diet (arMED) score excluding alcohol. Cox proportional hazards regression models were used while adjusting for BC risk factors. A total of 9,009 postmenopausal and 1,216 premenopausal first primary incident invasive BC were identified (5,862 estrogen or progesterone receptor positive [ER+/PR+] and 1,018 estrogen and progesterone receptor negative [ER-/PR-]). The arMED was inversely associated with the risk of BC overall and in postmenopausal women (high vs. low arMED score; hazard ratio [HR] = 0.94 [95% confidence interval [CI]: 0.88, 1.00] ptrend = 0.048, and HR = 0.93 [95% CI: 0.87, 0.99] ptrend = 0.037, respectively). The association was more pronounced in ER-/PR- tumors (HR = 0.80 [95% CI: 0.65, 0.99] ptrend = 0.043). The arMED score was not associated with BC in premenopausal women. Our findings show that adherence to a MD excluding alcohol was related to a modest reduced risk of BC in postmenopausal women, and this association was stronger in receptor-negative tumors. The results support the potential scope for BC prevention through dietary modification.

The link between family history and risk of type 2 diabetes is not explained by anthropometric, lifestyle or genetic risk factors: the EPIC-InterAct study.

AIMS/HYPOTHESIS: Although a family history of type 2 diabetes is a strong risk factor for the disease, the factors mediating this excess risk are poorly understood. In the InterAct case-cohort study, we investigated the association between a family history of diabetes among different family members and the incidence of type 2 diabetes, as well as the extent to which genetic, anthropometric and lifestyle risk factors mediated this association. METHODS: A total of 13,869 individuals (including 6,168 incident cases of type 2 diabetes) had family history data available, and 6,887 individuals had complete data on all mediators. Country-specific Prentice-weighted Cox models were fitted within country, and HRs were combined using random effects meta-analysis. Lifestyle and anthropometric measurements were performed at baseline, and a genetic risk score comprising 35 polymorphisms associated with type 2 diabetes was created. RESULTS: A family history of type 2 diabetes was associated with a higher incidence of the condition (HR 2.72, 95% CI 2.48, 2.99). Adjustment for established risk factors including BMI and waist circumference only modestly attenuated this association (HR 2.44, 95% CI 2.03, 2.95); the genetic score alone explained only 2% of the family history-associated risk of type 2 diabetes. The greatest risk of type 2 diabetes was observed in those with a biparental history of type 2 diabetes (HR 5.14, 95% CI 3.74, 7.07) and those whose parents had been diagnosed with diabetes at a younger age (<50 years; HR 4.69, 95% CI 3.35, 6.58), an effect largely confined to a maternal family history. CONCLUSIONS/INTERPRETATION: Prominent lifestyle, anthropometric and genetic risk factors explained only a marginal proportion of the excess risk associated with family history, highlighting the fact that family history remains a strong, independent and easily assessed risk factor for type 2 diabetes. Discovering factors that will explain the association of family history with type 2 diabetes risk will provide important insight into the aetiology of type 2 diabetes.

Alcohol dehydrogenase and aldehyde dehydrogenase gene polymorphisms, alcohol intake and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study.

BACKGROUND/OBJECTIVES: Heavy alcohol drinking is a risk factor of colorectal cancer (CRC), but little is known on the effect of polymorphisms in the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) on the alcohol-related risk of CRC in Caucasian populations. SUBJECTS/METHODS: A nested case-control study (1269 cases matched to 2107 controls by sex, age, study centre and date of blood collection) was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the impact of rs1229984 (ADH1B), rs1573496 (ADH7) and rs441 (ALDH2) polymorphisms on CRC risk. Using the wild-type variant of each polymorphism as reference category, CRC risk estimates were calculated using conditional logistic regression, with adjustment for matching factors. RESULTS: Individuals carrying one copy of the rs1229984(A) (ADH1B) allele (fast metabolizers) showed an average daily alcohol intake of 4.3 g per day lower than subjects with two copies of the rs1229984(G) allele (slow metabolizers) (P(diff)<0.01). None of the polymorphisms was associated with risk of CRC or cancers of the colon or rectum. Heavy alcohol intake was more strongly associated with CRC risk among carriers of the rs1573496(C) allele, with odds ratio equal to 2.13 (95% confidence interval: 1.26-3.59) compared with wild-type subjects with low alcohol consumption (P(interaction)=0.07). CONCLUSIONS: The rs1229984(A) (ADH1B) allele was associated with a reduction in alcohol consumption. The rs1229984 (ADH1B), rs1573496 (ADH7) and rs441 (ALDH2) polymorphisms were not associated with CRC risk overall in Western-European populations. However, the relationship between alcohol and CRC risk might be modulated by the rs1573496 (ADH7) polymorphism.