International Pooled Analysis of Leisure-Time Physical Activity and Premenopausal Breast Cancer in Women From 19 Cohorts.

PURPOSE: There is strong evidence that leisure-time physical activity is protective against postmenopausal breast cancer risk but the association with premenopausal breast cancer is less clear. The purpose of this study was to examine the association of physical activity with the risk of developing premenopausal breast cancer. METHODS: We pooled individual-level data on self-reported leisure-time physical activity across 19 cohort studies comprising 547,601 premenopausal women, with 10,231 incident cases of breast cancer. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% CIs for associations of leisure-time physical activity with breast cancer incidence. HRs for high versus low levels of activity were based on a comparison of risk at the 90th versus 10th percentiles of activity. We assessed the linearity of the relationship and examined subtype-specific associations and effect modification across strata of breast cancer risk factors, including adiposity. RESULTS: Over a median 11.5 years of follow-up (IQR, 8.0-16.1 years), high versus low levels of leisure-time physical activity were associated with a 6% (HR, 0.94 [95% CI, 0.89 to 0.99]) and a 10% (HR, 0.90 [95% CI, 0.85 to 0.95]) reduction in breast cancer risk, before and after adjustment for BMI, respectively. Tests of nonlinearity suggested an approximately linear relationship (Pnonlinearity = .94). The inverse association was particularly strong for human epidermal growth factor receptor 2-enriched breast cancer (HR, 0.57 [95% CI, 0.39 to 0.84]; Phet = .07). Associations did not vary significantly across strata of breast cancer risk factors, including subgroups of adiposity. CONCLUSION: This large, pooled analysis of cohort studies adds to evidence that engagement in higher levels of leisure-time physical activity may lead to reduced premenopausal breast cancer risk.

The association of women's birth size with risk of molecular breast cancer subtypes: a cohort study.

BACKGROUND: Because birth size appears to be positively associated with breast cancer risk, we have studied whether this risk may differ according to molecular breast cancer subtypes. METHODS: A cohort of 22,931 women born 1920-1966 were followed up for breast cancer occurrence from 1961 to 2012, and 870 were diagnosed during follow-up. Archival diagnostic material from 537 patients was available to determine molecular breast cancer subtype, specified as Luminal A, Luminal B (human epidermal growth factor receptor 2 (HER2)-), Luminal B (HER2+), HER2 type, and Triple negative (TN) breast cancer. Information on the women's birth weight, birth length and head circumference at birth was used to estimate hazard ratios (HR) with 95% confidence intervals (CI) for each molecular subtype, applying Cox regression, and stratified by maternal height. RESULTS: Birth length (per 2 cm increments) was positively associated with Luminal A (HR = 1.2, 95% CI, 1.0-1.3), Luminal B (HER2+) (HR = 1.3, 95% CI, 1.0-1.7), and TN breast cancer (HR = 1.4, 95% CI, 1.0-1.9). No clear association was found for birth weight and head circumference. The positive associations of birth length were restricted to women whose mothers were relatively tall (above population median). CONCLUSION: We found a positive association of birth length with risk of Luminal A, Luminal B (HER2+) and TN breast cancer that appears to be restricted to women whose mothers were relatively tall. This may support the hypothesis that breast cancer risk is influenced by determinants of longitudinal growth and that this finding deserves further scrutiny.

Menopausal hormone therapy and breast cancer risk: effect modification by body mass through life.

It is not known whether increased breast cancer risk caused by menopausal hormone therapy (HT) depends on body mass patterns through life. In a prospective study of 483,241 Norwegian women aged 50-69 years at baseline, 7656 women developed breast cancer during follow-up (2006-2013). We combined baseline information on recalled body mass in childhood/adolescence and current (baseline) body mass index (BMI) to construct mutually exclusive life-course body mass patterns. We assessed associations of current HT use with breast cancer risk according to baseline BMI and life-course patterns of body mass, and estimated relative excess risk due to interaction (RERI). Within all levels of baseline BMI, HT use was associated with increased risk. Considering life-course body mass patterns as a single exposure, we used women who "remained at normal weight" through life as the reference, and found that being "overweight as young" was associated with lower risk (hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.76-0.94), whereas women who "gained weight" had higher risk (HR 1.20, 95% CI 1.12-1.28). Compared to never users of HT who were "overweight as young", HT users who either "remained at normal weight" or "gained weight" in adulthood were at higher risk than expected when adding the separate risks (RERI 0.52, 95% CI 0.09-0.95, and RERI 0.37, 95% CI - 0.07-0.80), suggesting effect modification. Thus, we found that women who remain at normal weight or gain weight in adulthood may be more susceptible to the risk increasing effect of HT compared to women who were overweight as young.

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.

Characterization of FGD5 Expression in Primary Breast Cancers and Lymph Node Metastases.

Faciogenital dysplasia 5 ( FGD5) amplification drives tumor cell proliferation, and is present in 9.5% of breast cancers. We describe FGD5 expression, assess associations between FGD5 amplification and FGD5 expression, and assess FGD5 expression in relation to proliferation and prognosis. FGD5 immunohistochemistry was done on primary tumors ( n=829) and lymph node metastases ( n=231) from a cohort of Norwegian patients. We explored associations between FGD5 amplification, FGD5 expression, and proliferation, and analyzed the prognostic value of FGD5 expression by estimating cumulative risks of death and hazard ratios (HRs). We identified nuclear and cytoplasmic expression in 64% and 73% of primary tumors, respectively, and found an association between gene amplification and nuclear expression ( p=0.02). The proportion of cases with FGD5 expression was higher in lymph node metastases, compared with primary tumors ( p=0.004 for nuclear and p=0.001 for cytoplasmic staining). Neither proliferation nor prognosis was associated with FGD5 expression (age-adjusted HR 1.12 [95% confidence interval = 0.89-1.41] for nuclear expression; and 0.88 [95% CI = 0.70-1.12] for cytoplasmic expression). FGD5 is expressed in a high proportion of breast cancers and lymph node metastases. There was a correlation between FGD5 amplification and nuclear expression, but no association between FGD5 expression and proliferation or prognosis.

Corrigendum: Hypertension and the risk of endometrial cancer: a systematic review and meta-analysis of case-control and cohort studies.

This corrects the article DOI: 10.1038/srep44808.

Does Prophylactic Radiation Therapy to Avoid Gynecomastia in Patients With Prostate Cancer Increase the Risk of Breast Cancer?

PURPOSE: Prostate cancer (PC) patients who undergo antiandrogen monotherapy are offered prophylactic radiation therapy (PRT) to the breast buds to avoid gynecomastia. The aim of the present study was to evaluate whether the risk of breast cancer (BC) in men with PC as their first cancer diagnosis was influenced by PRT. METHODS AND MATERIALS: From the Norwegian Cancer Registry, we collected data from all patients with PC as their first cancer diagnosis from 1997 to 2014. We registered all RT given to the patients in the same period and the occurrence of BC diagnosed ≥3 months after the PC diagnosis. The histopathologic diagnoses of all BC cases were collected. Subdistribution hazard ratios for the risk of BC in the PRT and non-PRT groups were estimated. A standardized incidence ratio for BC was calculated by comparing our cohort to the standard male population. RESULTS: We analyzed 59,169 patients with PC, of whom 7864 (13.3%) had received PRT. The median follow-up time was 4 years. Of the 12 men with a diagnosis of BC, 3 had received PRT, and 2 of the 3 were phyllodes tumors. The risk of BC was not significantly different statistically for the patients given PRT compared with the non-PRT group (subdistribution hazard ratio 1.62, 95% confidence interval 0.41-5.62, adjusted for age and time of diagnosis). The standardized incidence ratio was 0.996 (95% confidence interval 0.57-1.75). CONCLUSIONS: In this registry-based study, we did not find an increased risk of BC in PC patients who received PRT. The number of BC cases in our study was low, and the risk of secondary BC after PRT seems to be negligible. The incidence of BC could, however, increase with additional follow-up. Also, 2 patients who had received PRT developed a malignant phyllodes tumor, an extremely rare type of BC associated with gynecomastia.

White Blood Cell BRCA1 Promoter Methylation Status and Ovarian Cancer Risk.

Background: The role of normal tissue gene promoter methylation in cancer risk is poorly understood. Objective: To assess associations between normal tissue BRCA1 methylation and ovarian cancer risk. Design: 2 case-control (initial and validation) studies. Setting: 2 hospitals in Norway (patients) and a population-based study (control participants). Participants: 934 patients and 1698 control participants in the initial study; 607 patients and 1984 control participants in the validation study. Measurements: All patients had their blood sampled before chemotherapy. White blood cell (WBC) BRCA1 promoter methylation was determined by using methylation-specific quantitative polymerase chain reaction, and the percentage of methylation-positive samples was compared between population control participants and patients with ovarian cancer, including the subgroup with high-grade serous ovarian cancer (HGSOC). Results: In the initial study, BRCA1 methylation was more frequent in patients with ovarian cancer than control participants (6.4% vs. 4.2%; age-adjusted odds ratio [OR], 1.83 [95% CI, 1.27 to 2.63]). Elevated methylation, however, was restricted to patients with HGSOC (9.6%; OR, 2.91 [CI, 1.85 to 4.56]), in contrast to 5.1% and 4.0% of patients with nonserous and low-grade serous ovarian cancer (LGSOC), respectively. These findings were replicated in the validation study (methylation-positive status in 9.1% of patients with HGSOC vs. 4.3% of control participants-OR, 2.22 [CI 1.40 to 3.52]-4.1% of patients with nonserous ovarian cancer, and 2.7% of those with LGSOC). The results were not influenced by tumor burden, storage time, or WBC subfractions. In separate analyses of young women and newborns, BRCA1 methylation was detected in 4.1% (CI, 1.8% to 6.4%) and 7.0% (CI, 5.0% to 9.1%), respectively. Limitations: Patients with ovarian cancer were recruited at the time of diagnosis in a hospital setting. Conclusion: Constitutively normal tissue BRCA1 promoter methylation is positively associated with risk for HGSOC. Primary Funding Source: Norwegian Cancer Society.

Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma.

BACKGROUND: Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings. OBJECTIVE: We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations. DESIGN, SETTING, AND PARTICIPANTS: Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis. RESULTS AND LIMITATIONS: Longer genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p<0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R2>0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, p<0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N=5573, OR=1.93, 95% CI=1.50-2.49, p<0.0001), papillary (N=573, OR=1.96, 95% CI=1.01-3.81, p=0.046), and chromophobe RCC (N=203, OR=2.37, 95% CI=0.78-7.17, p=0.13). CONCLUSIONS: Our investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk. PATIENT SUMMARY: Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma.

Monocyte/macrophage and T cell activation markers are not independently associated with MI risk in healthy individuals - results from the HUNT Study.

BACKGROUND: We hypothesized that circulating markers reflecting monocyte/macrophage and T cell activation are associated with increased risk of myocardial infarction (MI) in apparently healthy individuals. METHODS: Serum monocyte/macrophage and T cell activation markers soluble (s) CD163, sCD14, Gal3BP, sCD25 and sCD166 were analyzed by enzyme-immunoassay in a case-control study nested within the population-based HUNT2 cohort in Norway. Among 58,761 apparently healthy men and women followed a median 11.3years, 1587 incident MI cases were registered, and compared to 3959 age- and sex-matched controls. RESULTS: Higher serum sCD163 (Q4 vs. Q1 OR: 1.27, P-trend 0.002), sCD14 (Q4 vs. Q1 OR: 1.38, P-trend<0.001), and especially sCD25 (Q4 vs. Q1 OR: 1.45, P-trend<0.001), were associated with increased MI risk in the age-and sex adjusted models. However, after additional adjustment for cardiovascular risk factors these associations were strongly attenuated (Q4 vs Q1 ORs between 1.02 and 1.12, P-trends between 0.30 and 0.58). CONCLUSIONS: sCD163, sCD14 and sCD25 may reflect leukocyte activation and inflammatory mechanisms related to atherogenesis, but do not predict MI risk above and beyond conventional cardiovascular risk factors.

Placental weight in the first pregnancy and risk for preeclampsia in the second pregnancy: A population-based study of 186 859 women.

OBJECTIVE: To study whether placental weight in the first pregnancy is associated with preeclampsia in the second pregnancy. STUDY DESIGN: In this population-based study, we included all women with two consecutive singleton pregnancies reported to the Medical Birth Registry of Norway during 1999-2012 (n=186 859). Placental weight in the first pregnancy was calculated as z-scores, and the distribution was divided into five groups of equal size (quintiles). We estimated crude and adjusted odds ratios with 95% confidence intervals for preeclampsia in the second pregnancy according to quintiles of placental weight z-scores in the first pregnancy. The 3rd quintile was used as the reference group. RESULTS: Among women without preeclampsia in the first pregnancy, 1.4% (2507/177 149) developed preeclampsia in the second pregnancy. In these women, the risk for preeclampsia in the second pregnancy was associated with placental weight in the first pregnancy in both lowest (crude odds ratio (cOR) 1.30, 95% confidence interval (CI); 1.14-1.47) and highest quintile (cOR 1.20, 95% CI; 1.06-1.36). The risk associated with the highest quintile of placental weight was confined to term preeclampsia. Among women with preeclampsia in the first pregnancy, 15.7% (1522/9710) developed recurrent preeclampsia, and the risk for recurrent preeclampsia was associated with placental weight in lowest quintile in the first pregnancy (cOR 1.30, 95% CI; 1.10-1.55). Adjustment for interval between pregnancies, maternal diabetes, age, and smoking in the first pregnancy did not alter these estimates notably. CONCLUSION: Placental weight in the first pregnancy might help to identify women who could be at risk for developing preeclampsia in a second pregnancy.

Reproductive and hormonal risk factors of breast cancer: a historical perspective.

The complexity of breast cancer etiology has puzzled scientists for more than 300 years. In this brief review, we emphasize the importance of reproductive and hormonal factors in relation to the risk of breast cancer. By following the historical course of how various risk factors have been determined, this study attempts to illustrate the origin of hypotheses, their subsequent rejection, and development of new hypotheses. Starting with the contributions of Italian physicians in the 18th century and covering the activity of British epidemiologists before World War II, this review ends up with the international collaboration that became increasingly important in the second half of the 20th century.

Hypertension and the risk of endometrial cancer: a systematic review and meta-analysis of case-control and cohort studies.

A history of hypertension has been associated with increased risk of endometrial cancer in several studies, but the results have not been consistent. We conducted a systematic review and meta-analysis of case-control and cohort studies to clarify the association between hypertension and endometrial cancer risk. PubMed and Embase databases were searched up to 27th of February 2016. Prospective and case-control studies which reported adjusted relative risk estimates and 95% confidence intervals of endometrial cancer associated with a hypertension diagnosis were included. Summary relative risks were estimated using a random effects model. Nineteen case-control studies and 6 cohort studies were included. The summary RR was 1.61 (95% CI: 1.41-1.85, I2 = 86%) for all studies, 1.73 (95% CI: 1.45-2.06, I2 = 89%) for case-control studies and 1.32 (95% CI: 1.12-1.56, I2 = 47%) for cohort studies. The association between hypertension and endometrial cancer was weaker, but still significant, among studies with adjustment for smoking, BMI, oral contraceptive use, and parity, compared to studies without such adjustment. This meta-analysis suggest an increased risk of endometrial cancer among patients with hypertension, however, further studies with more comprehensive adjustments for confounders are warranted to clarify the association.

Body mass index and physical activity and the risk of diverticular disease: a systematic review and meta-analysis of prospective studies.

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.

Fruit and vegetable intake and the risk of cardiovascular disease, total cancer and all-cause mortality-a systematic review and dose-response meta-analysis of prospective studies.

Background: Questions remain about the strength and shape of the dose-response relationship between fruit and vegetable intake and risk of cardiovascular disease, cancer and mortality, and the effects of specific types of fruit and vegetables. We conducted a systematic review and meta-analysis to clarify these associations. Methods: PubMed and Embase were searched up to 29 September 2016. Prospective studies of fruit and vegetable intake and cardiovascular disease, total cancer and all-cause mortality were included. Summary relative risks (RRs) were calculated using a random effects model, and the mortality burden globally was estimated; 95 studies (142 publications) were included. Results: For fruits and vegetables combined, the summary RR per 200 g/day was 0.92 [95% confidence interval (CI): 0.90-0.94, I 2 = 0%, n = 15] for coronary heart disease, 0.84 (95% CI: 0.76-0.92, I 2 = 73%, n = 10) for stroke, 0.92 (95% CI: 0.90-0.95, I 2 = 31%, n = 13) for cardiovascular disease, 0.97 (95% CI: 0.95-0.99, I 2 = 49%, n = 12) for total cancer and 0.90 (95% CI: 0.87-0.93, I 2 = 83%, n = 15) for all-cause mortality. Similar associations were observed for fruits and vegetables separately. Reductions in risk were observed up to 800 g/day for all outcomes except cancer (600 g/day). Inverse associations were observed between the intake of apples and pears, citrus fruits, green leafy vegetables, cruciferous vegetables, and salads and cardiovascular disease and all-cause mortality, and between the intake of green-yellow vegetables and cruciferous vegetables and total cancer risk. An estimated 5.6 and 7.8 million premature deaths worldwide in 2013 may be attributable to a fruit and vegetable intake below 500 and 800 g/day, respectively, if the observed associations are causal. Conclusions: Fruit and vegetable intakes were associated with reduced risk of cardiovascular disease, cancer and all-cause mortality. These results support public health recommendations to increase fruit and vegetable intake for the prevention of cardiovascular disease, cancer, and premature mortality.

Cardiovascular mortality - Comparing risk factor associations within couples and in the total population - The HUNT Study.

BACKGROUND: To compare associations of conventional risk factors with cardiovascular death within couples and in the population as a whole. METHODS: We analysed baseline data (1995-97) from the HUNT2 Study in Norway linked to the national Causes of Death Registry. We compared risk within couples using stratified Cox regression. RESULTS: During 914776 person-years, 3964 cardiovascular deaths occurred, and 1658 of the deaths occurred among 1494 couples. There were consistently stronger associations of serum lipids and blood pressure with cardiovascular mortality within couples compared to the population as a whole. For instance, for systolic blood pressure (per 20mmHg), the hazard ratio (HR) within couples was 1.28 (95% confidence interval: 1.17, 1.40) compared to 1.16 (1.12, 1.20) in the total population, and for diastolic pressure (per 10mmHg), the corresponding HRs were 1.16 (1.07, 1.26) and 1.11 (1.08, 1.13). Anthropometric factors (BMI, waist circumference, waist-hip ratio) as well as diabetes, smoking, physical activity, and education, showed nearly identical positive associations within couples and in the total population. CONCLUSIONS: Prospective population studies may tend to slightly underestimate associations of these factors with cardiovascular mortality.

Cohort Profile: The Polish-Norwegian Study (PONS) cohort.

The PONS cohort is a longitudinal observational regional study collecting information on health and health-related behaviours in the south-eastern part of Poland. The study aims at providing information on determinants of health differences between Poland and other countries in the region, especially related to premature mortality. The baseline data collection contains records for 13 172 individuals (2010-11), between 45 and 64 years of age, from the city of Kielce and surrounding rural area. All cohort members were volunteer participants and gave informed consent prior to inclusion. Data were collected on current health status, medical history and health-related behaviours with focus on preventable causes of chronic diseases, including tobacco smoking, alcohol consumption, physical activity and dietary habits. In addition to an extensive questionnaire, blood and urine samples were collected for storage. The study is expected to provide valuable evidence related to various lifestyle behaviours and health, and insight into the usefulness of population approaches for preventive interventions in Polish communities. To access data or biological material or to use the sample to recruit participants for new studies, researchers should contact the principal investigator, Witold A Zatonski at: [canepid@coi.waw.pl].

Nut consumption and risk of cardiovascular disease, total cancer, all-cause and cause-specific mortality: a systematic review and dose-response meta-analysis of prospective studies.

BACKGROUND: Although nut consumption has been associated with a reduced risk of cardiovascular disease and all-cause mortality, data on less common causes of death has not been systematically assessed. Previous reviews missed several studies and additional studies have since been published. We therefore conducted a systematic review and meta-analysis of nut consumption and risk of cardiovascular disease, total cancer, and all-cause and cause-specific mortality. METHODS: PubMed and Embase were searched for prospective studies of nut consumption and risk of cardiovascular disease, total cancer, and all-cause and cause-specific mortality in adult populations published up to July 19, 2016. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models. The burden of mortality attributable to low nut consumption was calculated for selected regions. RESULTS: Twenty studies (29 publications) were included in the meta-analysis. The summary RRs per 28 grams/day increase in nut intake was for coronary heart disease, 0.71 (95% CI: 0.63-0.80, I2 = 47%, n = 11), stroke, 0.93 (95% CI: 0.83-1.05, I2 = 14%, n = 11), cardiovascular disease, 0.79 (95% CI: 0.70-0.88, I2 = 60%, n = 12), total cancer, 0.85 (95% CI: 0.76-0.94, I2 = 42%, n = 8), all-cause mortality, 0.78 (95% CI: 0.72-0.84, I2 = 66%, n = 15), and for mortality from respiratory disease, 0.48 (95% CI: 0.26-0.89, I2 = 61%, n = 3), diabetes, 0.61 (95% CI: 0.43-0.88, I2 = 0%, n = 4), neurodegenerative disease, 0.65 (95% CI: 0.40-1.08, I2 = 5.9%, n = 3), infectious disease, 0.25 (95% CI: 0.07-0.85, I2 = 54%, n = 2), and kidney disease, 0.27 (95% CI: 0.04-1.91, I2 = 61%, n = 2). The results were similar for tree nuts and peanuts. If the associations are causal, an estimated 4.4 million premature deaths in the America, Europe, Southeast Asia, and Western Pacific would be attributable to a nut intake below 20 grams per day in 2013. CONCLUSIONS: Higher nut intake is associated with reduced risk of cardiovascular disease, total cancer and all-cause mortality, and mortality from respiratory disease, diabetes, and infections.

Whole grain consumption and risk of cardiovascular disease, cancer, and all cause and cause specific mortality: systematic review and dose-response meta-analysis of prospective studies.

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.