Intakes of specific fatty acids have been postulated to impact breast cancer risk but epidemiological data based on dietary questionnaires remain conflicting.
We assessed the association between ...plasma phospholipid fatty acids and breast cancer risk in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition study. Sixty fatty acids were measured by gas chromatography in pre-diagnostic plasma phospholipids from 2982 incident breast cancer cases matched to 2982 controls. Conditional logistic regression models were used to estimate relative risk of breast cancer by fatty acid level. The false discovery rate (q values) was computed to control for multiple comparisons. Subgroup analyses were carried out by estrogen receptor (ER) and progesterone receptor expression in the tumours.
A high level of palmitoleic acid odds ratio (OR) for the highest quartile compared with the lowest OR (Q4–Q1) 1.37; 95% confidence interval (CI), 1.14–1.64; P for trend=0.0001, q value=0.004 as well as a high desaturation index (DI16) (16:1n–7/16:0) OR (Q4–Q1), 1.28; 95% C, 1.07–1.54; P for trend=0.002, q value=0.037, as biomarkers of de novo lipogenesis, were significantly associated with increased risk of breast cancer. Levels of industrial trans-fatty acids were positively associated with ER-negative tumours OR for the highest tertile compared with the lowest (T3–T1)=2.01; 95% CI, 1.03–3.90; P for trend=0.047, whereas no association was found for ER-positive tumours (P-heterogeneity=0.01). No significant association was found between n-3 polyunsaturated fatty acids and breast cancer risk, overall or by hormonal receptor.
These findings suggest that increased de novo lipogenesis, acting through increased synthesis of palmitoleic acid, could be a relevant metabolic pathway for breast tumourigenesis. Dietary trans-fatty acids derived from industrial processes may specifically increase ER-negative breast cancer risk.
Aims/hypothesis We examined the association between serum C-reactive protein (CRP) and incident diabetes in a prospective study, and added these data to a literature-based meta-analysis to explore ...potential sources of heterogeneity between studies. Methods We analysed a case-control study nested within the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort, including 293 incident diabetes cases and 708 controls. We combined 16 published studies on CRP and incident diabetes in a random-effect meta-analysis. Results In the EPIC-Norfolk cohort, serum CRP was associated with a higher risk of diabetes after adjusting for age, sex, BMI, family history of diabetes, smoking and physical activity (OR 1.49, comparing the extreme thirds of CRP distribution 95% CI 1.03-2.15, p = 0.03). However, the association was completely attenuated after further adjustment for WHR, serum γ-glutamyltransferase and serum adiponectin (OR 1.00; 95% CI 0.66-1.51, p = 1.0). In a meta-analysis of 16 published studies with 3,920 incident diabetes cases and 24,914 controls, the RR was 1.72 (95% CI 1.54-1.92), comparing the extreme thirds of CRP distribution, with substantial heterogeneity between studies (I ² = 52.8%, p = 0.007). Conclusions/interpretation Initial evidence of association between CRP and incident diabetes was confounded by central adiposity, markers of liver dysfunction and adiponectin in the primary analysis. Despite an overall positive association in the meta-analysis, considerable heterogeneity existed between studies. The degree of adjustment for central adiposity and baseline glycaemia explained some of this heterogeneity and suggests that CRP may not be an independent risk factor for type 2 diabetes.
Diets high in vegetables and fruits have been suggested to be inversely associated with risk of gastric cancer. However, the evidence of the effect of variety of consumption is limited. We therefore ...investigated whether consumption of a variety of vegetables and fruit is associated with gastric and esophageal cancer in the European Prospective Investigation into Cancer and Nutrition study. Data on food consumption and follow‐up on cancer incidence were available for 452,269 participants from 10 European countries. After a mean follow‐up of 8.4 years, 475 cases of gastric and esophageal adenocarcinomas (180 noncardia, 185 cardia, gastric esophageal junction and esophagus, 110 not specified) and 98 esophageal squamous cell carcinomas were observed. Diet Diversity Scores were used to quantify the variety in vegetable and fruit consumption. We used multivariable Cox proportional hazard models to calculate risk ratios. Independent from quantity of consumption, variety in the consumption of vegetables and fruit combined and of fruit consumption alone were statistically significantly inversely associated with the risk of esophageal squamous cell carcinoma (continuous hazard ratio per 2 products increment 0.88; 95% CI 0.79–0.97 and 0.76; 95% CI 0.62–0.94, respectively) with the latter particularly seen in ever smokers. Variety in vegetable and/or fruit consumption was not associated with risk of gastric and esophageal adenocarcinomas. Independent from quantity of consumption, more variety in vegetable and fruit consumption combined and in fruit consumption alone may decrease the risk of esophageal squamous cell carcinoma. However, residual confounding by lifestyle factors cannot be excluded.
Aims/hypothesis
There has been long-standing debate about whether diabetes is a causal risk factor for pancreatic cancer or a consequence of tumour development. Prospective epidemiological studies ...have shown variable relationships between pancreatic cancer risk and blood markers of glucose and insulin metabolism, overall and as a function of lag times between marker measurements (blood donation) and date of tumour diagnosis.
Methods
Pre-diagnostic levels of HbA
1c
and C-peptide were measured for 466 participants with pancreatic cancer and 466 individually matched controls within the European Prospective Investigation into Cancer and Nutrition. Conditional logistic regression models were used to estimate ORs for pancreatic cancer.
Results
Pancreatic cancer risk gradually increased with increasing pre-diagnostic HbA
1c
levels up to an OR of 2.42 (95% CI 1.33, 4.39 highest ≥6.5%, 48 mmol/mol vs lowest ≤5.4%, 36 mmol/mol category), even for individuals with HbA
1c
levels within the non-diabetic range. C-peptide levels showed no significant relationship with pancreatic cancer risk, irrespective of fasting status. Analyses showed no clear trends towards increasing hyperglycaemia (as marked by HbA
1c
levels) or reduced pancreatic beta cell responsiveness (as marked by C-peptide levels) with decreasing time intervals from blood donation to cancer diagnosis.
Conclusions/interpretation
Our data on HbA
1c
show that individuals who develop exocrine pancreatic cancer tend to have moderate increases in HbA
1c
levels, relatively independently of obesity and insulin resistance—the classic and major risk factors for type 2 diabetes. While there is no strong difference by lag time, more data are needed on this in order to reach a firm conclusion.
The role of long-term alcohol consumption for the risk of developing ulcerative colitis (UC) and Crohn's disease (CD) is unclear. For the first time, to prospectively assess the role of pre-disease ...alcohol consumption on the risk of developing UC or CD.
Nested within the European Prospective Investigation into Cancer and Nutrition (EPIC-IBD), incident UC and CD cases and matched controls where included. At recruitment, participants completed validated food frequency and lifestyle questionnaires. Alcohol consumption was classified as either: non-use, former, light (⩽0.5 and 1 drink per week), below the recommended limits (BRL) (⩽1 and 2 drinks per day), moderate (⩽2.5 and 5 drinks per day), or heavy use (>2.5 and >5 drinks per day) for women and men, respectively; and was expressed as consumption at enrolment and during lifetime. Conditional logistic regression was applied adjusting for smoking and education, taking light users as the reference.
Out of 262 451 participants in six countries, 198 UC incident cases/792 controls and 84 CD cases/336 controls were included. At enrolment, 8%/27%/32%/23%/11% UC cases and 7%/29%/40%/19%/5% CD cases were: non-users, light, BRL, moderate and heavy users, respectively. The corresponding figures for lifetime non-use, former, light, BRL, moderate and heavy use were: 3%/5%/23%/44%/19%/6% and 5%/2%/25%/44%/23%/1% for UC and CD cases, respectively. There were no associations between any categories of alcohol consumption and risk of UC or CD in the unadjusted and adjusted odds ratios.
There was no evidence of associations between alcohol use and the odds of developing either UC or CD.
Objective: To test the hypothesis that for any given body mass index (BMI) category, active individuals would have a smaller waist circumference than inactive individuals. Our second objective was to ...examine the respective contribution of waist circumference and physical inactivity on coronary heart disease (CHD) risk. Design: Prospective, population-based study with an 11.4-year follow-up. Subjects: A total of 21 729 men and women aged 45-79 years, residing in Norfolk, UK. Methods: During follow-up, 2191 CHD events were recorded. Physical activity was evaluated using a validated lifestyle questionnaire that takes into account both leisure-time and work-related physical activity. Waist circumference was measured and BMI was calculated for each participant. Results: For both men and women, we observed that within each BMI category (<25.0, 25-30 and > or = 30.0 kg m-2), active participants had a lower waist circumference than inactive participants (P<0.001). In contrast, within each waist circumference tertile, BMI did not change across physical activity categories (except for women with an elevated waist circumference). Compared with active men with a low waist circumference, inactive men with an elevated waist circumference had a hazard ratio (HR) for future CHD of 1.74 (95% confidence interval (CI), 1.34-2.27) after adjusting for age, smoking, alcohol intake and parental history of CHD. In the same model and after further adjusting for hormone replacement therapy use, compared with active women with a low waist circumference, inactive women with an elevated waist circumference had an HR for future CHD of 4.00 (95% CI, 2.04-7.86). Conclusion: In any BMI category, inactive participants were characterized by an increased waist circumference, a marker of abdominal adiposity, compared with active individuals. Physical inactivity and abdominal obesity were both independently associated with an increased risk of future CHD.
Background: Several antioxidant nutrients have been reported to be inversely associated with asthma. A study was undertaken to assess the independent associations of these nutrients with asthma in ...adults. Methods: A nested case-control study was performed in 515 adults with physician diagnosed asthma and 515 matched controls using dietary data obtained from 7 day food diaries. The main outcome measures were physician diagnosed asthma and current symptomatic asthma (diagnosed asthma and self-reported wheeze within the previous 12 months). Results: Cases were similar to controls in age, sex, social class, and daily energy intake but had a lower median intake of fruit (132.1 v 149.1 g/day, p⩽0.05). 51.5% of the population reported zero consumption of citrus fruit; relative to these individuals, people who consumed >46.3 g/day had a reduced risk of diagnosed and symptomatic asthma (OR adjusted for potential confounders 0.59 (95% CI 0.43 to 0.82) and 0.51 (95% CI 0.33 to 0.79), respectively). In nutrient analysis, dietary vitamin C and manganese were inversely and independently associated with symptomatic asthma (adjusted OR per quintile increase 0.88 (95% CI 0.77 to 1.00) for vitamin C and 0.85 (95% CI 0.74 to 0.98) for manganese), but only manganese was independently associated with diagnosed asthma (OR 0.86 (95% CI 0.77 to 0.95)). Adjusted plasma levels of vitamin C were significantly lower in symptomatic cases than in controls (54.3 v 58.2 μmol/l, p = 0.003). Conclusions: Symptomatic asthma in adults is associated with a low dietary intake of fruit, the antioxidant nutrients vitamin C and manganese, and low plasma vitamin C levels. These findings suggest that diet may be a potentially modifiable risk factor for the development of asthma.
Aims/hypothesis The aim of this study was to examine the association between baseline body iron stores and new-onset diabetes. Subjects and methods We studied the association between baseline serum ...ferritin concentration and type 2 diabetes in 360 clinically incident diabetes cases and 758 controls nested within the EPIC (European Prospective Investigation of Cancer)-Norfolk Cohort Study. Serum ferritin levels were categorised into five groups: sex-specific quartiles of the normal range of ferritin and a group with clinically raised ferritin below levels indicative of haemochromatosis. Results Baseline serum ferritin was higher among cases than control participants (geometric mean: men 96.6 vs 67.8 ng/ml, respectively, p < 0.001; women 45.9 vs 34.8 ng/ml, respectively, p = 0.005). In analyses adjusted for known risk factors (age, BMI, sex, family history, physical activity, smoking habit) and dietary factors measured by 7-day food diary, the risk of diabetes was markedly elevated in participants with clinically raised ferritin compared with the lowest quartile (odds ratio OR 7.4, 95% CI 3.5-15.4). Further adjustment for potential confounding by inflammation (C-reactive protein, IL-6 and fibrinogen) had no material impact on the observed association, while adjustment for hepatic enzymes (alanine aminotransferase and γ glutamyl transferase) and adiponectin attenuated the magnitude of association, but it remained statistically significant (OR 3.2 1.3-7.6). Conclusions/interpretation Serum ferritin is an important and independent predictor of the development of diabetes. This finding may have important implications for understanding the aetiology of diabetes.
Objective To examine the association between fruit and vegetable consumption and risk of different histological subtypes of lung cancer among participants of the European Prospective Investigation ...into Cancer and Nutrition study. Methods Multivariable Cox proportional hazard models were used to analyze the data. A calibration study in a subsample was used to reduce dietary measurement errors. Results During a mean follow-up of 8.7 years, 1,830 incident cases of lung cancer (574 adenocarcinoma, 286 small cell, 137 large cell, 363 squamous cell, 470 other histologies) were identified. In line with our previous conclusions, we found that after calibration a 100 g/day increase in fruit and vegetables consumption was associated with a reduced lung cancer risk (HR 0.94; 95% CI 0.89-0.99). This was also seen among current smokers (HR 0.93; 95% CI 0.90-0.97). Risks of squamous cell carcinomas in current smokers were reduced for an increase of 100 g/day of fruit and vegetables combined (HR 0.85; 95% CI 0.76-0.94), while no clear effects were seen for the other histological subtypes. Conclusion We observed inverse associations between the consumption of vegetables and fruits and risk of lung cancer without a clear effect on specific histological subtypes of lung cancer. In current smokers, consumption of vegetables and fruits may reduce lung cancer risk, in particular the risk of squamous cell carcinomas.
Stress is thought to exert both positive and negative effects on cognition, but the precise cognitive effects of social stress and individuals' response to stress remain unclear. We aimed to ...investigate the association between different measures of social stress and cognitive function in a middle- to older-aged population using data from the European Prospective Investigation into Cancer (EPIC)-Norfolk study.
Participants completed a comprehensive assessment of lifetime social adversity between 1993 and 1997 and the short form of the Mini Mental State Examination (SF-MMSE), an assessment of global cognitive function, during the third health check between 2004 and 2011 (a median of 10.5 years later). A low MMSE score was defined as a score in the bottom quartile (20-26).
Completed MMSE scores and stress measures were available for 5129 participants aged 48-90 years. Participants who reported that their lives had been more stressful over the previous 10 years were significantly more likely to have low MMSE scores odds ratio (OR) 1.14, 95% confidence interval (CI) 1.04-1.24 per unit increase in perceived stress, independently of sociodemographic factors, physical and emotional health. The effects were restricted to the highest level of stress and the association was stronger among participants with a lower educational level. Adaptation following life event experiences also seemed to be associated with MMSE scores after adjusting for sociodemographic factors, but the association was attenuated with further adjustment.
In this generally high-functioning population, individuals' interpretations and responses to stressful events, rather than the events themselves, were associated with cognitive function.
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