Publications
363 results found
Laine J, Huybrechts I, Gunter M, et al., 2021, Co-benefits from sustainable dietary shifts for population and environmental health: an assessment from a large European cohort study, The Lancet Planetary Health, Vol: 5, Pages: e786-e796, ISSN: 2542-5196
Background: Unhealthy diets, the rise of non-communicable diseases, and the declining health of the planet are highly intertwined, where food production and consumption are major drivers of increases in greenhouse gas (GHG) emissions, substantial land use, (LU) and adverse health outcomes such as cancer and mortality. Methods: In the European Prospective Investigation into Cancer and Nutrition (EPIC), a multi-centre prospective cohort study (n=443,991), we estimated associations between dietary contributions to GHG emissions and LU and all-cause and cause-specific mortality and incident cancers using Cox proportional-hazard regression models. Co-benefits, encompassing the potential effects of alternative diets on all-cause mortality and cancer and potential reduction in GHG emissions and LU, were estimated using counterfactual attributable fraction (AF) intervention models, simulating potential effects from dietary shifts based on the EAT-Lancet reference diet. Findings: There was an association between levels of dietary-based GHG emissions and LU and all-cause mortality, with a Hazard Ratio and 95% Confidence Interval (CI) of 1.13 (1.10, 1.16) and 1.18 (95% CI: 1.15, 1.21), respectively, comparing the fourth quartile to the first (HRQ4 vs Q1). Similar associations were observed for cause-specific mortality. There were also associations between overall cancer rates and GHG emissions (HRQ4 vs Q1: 1.11, 95% CI: 1.09, 1.14) and LU (HRQ4 vs Q1: 1.13, 95% CI: 1.10, 1.15); however, estimates differed by cancer type. Through counterfactual AF modelling of shifts in diets, we find that between 19 to 63% of deaths and 10 to 39% of cancers could be prevented, over a 20-year risk period, from adhering to different scores of the EAT-Lancet reference diet. Additionally, switching from a lower score of the EAT-Lancet reference diet to a higher score could reduce food-associated GHG and LU levels by 50% and 62%, respectively.Interpretation: Our results support shifts in diets that
Hanley-Cook GT, Huybrechts I, Biessy C, et al., 2021, Food biodiversity and total and cause-specific mortality in 9 European countries: An analysis of a prospective cohort study, PLoS Medicine, Vol: 18, ISSN: 1549-1277
BackgroundFood biodiversity, encompassing the variety of plants, animals, and other organisms consumed as food and drink, has intrinsic potential to underpin diverse, nutritious diets and improve Earth system resilience. Dietary species richness (DSR), which is recommended as a crosscutting measure of food biodiversity, has been positively associated with the micronutrient adequacy of diets in women and young children in low- and middle-income countries (LMICs). However, the relationships between DSR and major health outcomes have yet to be assessed in any population.Methods and findingsWe examined the associations between DSR and subsequent total and cause-specific mortality among 451,390 adults enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) study (1992 to 2014, median follow-up: 17 years), free of cancer, diabetes, heart attack, or stroke at baseline. Usual dietary intakes were assessed at recruitment with country-specific dietary questionnaires (DQs). DSR of an individual’s yearly diet was calculated based on the absolute number of unique biological species in each (composite) food and drink. Associations were assessed by fitting multivariable-adjusted Cox proportional hazards regression models. In the EPIC cohort, 2 crops (common wheat and potato) and 2 animal species (cow and pig) accounted for approximately 45% of self-reported total dietary energy intake [median (P10–P90): 68 (40 to 83) species consumed per year]. Overall, higher DSR was inversely associated with all-cause mortality rate. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing total mortality in the second, third, fourth, and fifth (highest) quintiles (Qs) of DSR to the first (lowest) Q indicate significant inverse associations, after stratification by sex, age, and study center and adjustment for smoking status, educational level, marital status, physical activity, alcohol intake, and total energy intake, Mediterranean diet score, red
Christakoudi S, Tsilidis K, Evangelou E, et al., 2021, Association of body-shape phenotypes with imaging measures of body composition in the UK Biobank cohort: relevance to colon cancer risk, BMC Cancer, Vol: 21, Pages: 1-15, ISSN: 1471-2407
BackgroundBody mass index (BMI), waist and hip circumference are strongly correlated and do not reflect body composition. A Body Shape Index (ABSI) and Hip Index (HI) define waist and hip size among individuals with the same weight and height and would thus reflect body density. We examined differences in body composition between body-shape phenotypes defined with ABSI and HI and used this information to propose explanations for associations between body-shape phenotypes and colon cancer risk.MethodsWe used data from the UK Biobank Resource for 15,520 men, 16,548 women with dual-emission X-ray absorptiometry (DXA) measurements; 3997 men, 4402 women with magnetic resonance imaging (MRI) measurements; 200,289 men, 230,326 women followed-up for colon cancer. We defined body-shape phenotypes as: large-ABSI-small-HI (“apple”), small-ABSI-large-HI (“pear”), small-ABSI-small-HI (“slim”), large-ABSI-large-HI (“wide”). We evaluated differences in body composition in linear models and associations with colon cancer risk in Cox proportional hazards models adjusted for confounders and explored heterogeneity by BMI.ResultsAmong individuals with the same height and weight, visceral adipose tissue (VAT) was lowest for “pear” and highest for “apple”, while abdominal subcutaneous adipose tissue (ASAT) was lowest for “slim” and highest for “wide” phenotype. In the gynoid region, differences between “apple” and “pear” phenotypes were accounted for mainly by fat mass in women but by lean mass in men. In men, lean mass was inversely associated with waist size, while the pattern of gynoid fat resembled ASAT in women. Lean and fat mass were higher for higher BMI, but not hand grip strength. Compared to normal weight “pear”, the risk of colon cancer in men (1029 cases) was higher for “apple” phenotype for normal weight (hazard ratio HR =&thi
Al-Jafar R, Zografou Themeli M, Zaman S, et al., 2021, Effect of religious fasting in Ramadan on blood pressure: results from LORANS (London Ramadan Study) and a meta-analysis., Journal of the American Heart Association, Vol: 10, Pages: 1-36, ISSN: 2047-9980
Background Ramadan fasting is practiced by hundreds of millions every year. This ritual practice changes diet and lifestyle dramatically; thus, the effect of Ramadan fasting on blood pressure must be determined. Methods and Results LORANS (London Ramadan Study) is an observational study, systematic review, and meta-analysis. In LORANS, we measured systolic blood pressure (SBP) and diastolic blood pressure (DBP) of 85 participants before and right after Ramadan. In the systematic review, studies were retrieved from PubMed, Embase, and Scopus from inception to March 3, 2020. We meta-analyzed the effect from these studies and unpublished data from LORANS. We included observational studies that measured SBP and/or DBP before Ramadan and during the last 2 weeks of Ramadan or the first 2 weeks of the month after. Data appraisal and extraction were conducted by at least 2 reviewers in parallel. We pooled SBP and DBP using a random-effects model. The systematic review is registered with PROSPERO (International Prospective Register of Systematic Reviews; CRD42019159477). In LORANS, 85 participants were recruited; mean age was 45.6±15.9 years, and 52.9% (n=45) of participants were men. SBP and DBP after Ramadan fasting were lower by 7.29 mm Hg (-4.74 to -9.84) and 3.42 mm Hg (-1.73 to -5.09), even after adjustment for potential confounders. We identified 2778 studies of which 33 with 3213 participants were included. SBP and DBP after/before Ramadan were lower by 3.19 mm Hg (-4.43 to -1.96, I2=48%) and 2.26 mm Hg (-3.19 to -1.34, I2=66%), respectively. In subgroup analyses, lower blood pressures were observed in the groups who are healthy or have hypertension or diabetes but not in patients with chronic kidney disease. Conclusions Our study suggests beneficial effects of Ramadan fasting on blood pressure independent of changes in weight, total body water, and fat mass and supports recommendations for some government
Katsoulis M, Lai AG, Diaz-Ordaz K, et al., 2021, Identifying adults at high-risk for change in weight and BMI in England: a longitudinal, large-scale, population-based cohort study using electronic health records, The Lancet Diabetes and Endocrinology, Vol: 9, Pages: 681-694, ISSN: 2213-8595
BACKGROUND: Targeted obesity prevention policies would benefit from the identification of population groups with the highest risk of weight gain. The relative importance of adult age, sex, ethnicity, geographical region, and degree of social deprivation on weight gain is not known. We aimed to identify high-risk groups for changes in weight and BMI using electronic health records (EHR). METHODS: In this longitudinal, population-based cohort study we used linked EHR data from 400 primary care practices (via the Clinical Practice Research Datalink) in England, accessed via the CALIBER programme. Eligible participants were aged 18-74 years, were registered at a general practice clinic, and had BMI and weight measurements recorded between Jan 1, 1998, and June 30, 2016, during the period when they had eligible linked data with at least 1 year of follow-up time. We calculated longitudinal changes in BMI over 1, 5, and 10 years, and investigated the absolute risk and odds ratios (ORs) of transitioning between BMI categories (underweight, normal weight, overweight, obesity class 1 and 2, and severe obesity [class 3]), as defined by WHO. The associations of demographic factors with BMI transitions were estimated by use of logistic regression analysis, adjusting for baseline BMI, family history of cardiovascular disease, use of diuretics, and prevalent chronic conditions. FINDINGS: We included 2 092 260 eligible individuals with more than 9 million BMI measurements in our study. Young adult age was the strongest risk factor for weight gain at 1, 5, and 10 years of follow-up. Compared with the oldest age group (65-74 years), adults in the youngest age group (18-24 years) had the highest OR (4·22 [95% CI 3·86-4·62]) and greatest absolute risk (37% vs 24%) of transitioning from normal weight to overweight or obesity at 10 years. Likewise, adults in the youngest age group with overweight or obesity at baseline were also at highest risk to transition to a hig
Bassukas ID, Tsilidis KK, Spyridonos P, 2021, Advanced keratinocyte skin cancer is a tumor with considerable disease burden and aggressiveness, Archives of Dermatological Research, Vol: 313, Pages: 707-709, ISSN: 0340-3696
In a 2013 study published in this Journal, Dacosta Byfield et al. used MediCare data to extract reliable estimations of the incidence (I = 6.16) and prevalence (P = 10.31) rates of advanced keratinocyte skin cancer (aKSC) per 100,000 US population. These data unmask a considerable disease burden of aKSC (tumor stages ≥ 3) compared to the corresponding projected SEER predictions in 2019 of all invasive cases (tumor stages ≥ 1). According to its incidence, aKSC ranks 19th out of 29 major SEER registered neoplasms and has an average disease duration of 1.67 years, which is the second shortest disease duration next only to pancreatic carcinoma. Furthermore, in support of the high disease aggressiveness of aKSC and using a calibration approach, we calculated a mortality estimate of 4.64 per 100,000 and a 5-year survival rate of 21.8% for this tumor, which corresponds to positions of 13th and 5th out of 29 cancers among the SEER tracked malignancies, respectively. Taken together, these data indicate a considerable disease burden and biologic aggressiveness of aKSC.
Koutsonida M, Kanellopoulou A, Markozannes G, et al., 2021, Adherence to Mediterranean diet and cognitive abilities in the Greek cohort of Epirus Health Study, Nutrients, Vol: 13, ISSN: 2072-6643
The Mediterranean diet is commonly proposed as a major modifiable protective factor that may delay cognitive impairment in the elderly. The aim of the study was to investigate the cross-sectional association of adherence to the Mediterranean diet with cognitive abilities in a younger Greek population. A total of 1201 healthy adults aged 21–77 years (mean: 47.8) from the Epirus Health Study cohort were included in the analysis. Adherence to the Mediterranean diet was measured using the 14-point Mediterranean Diet Adherence Screener (MEDAS) and cognition was measured using the Trail Making Test, the Verbal Fluency test and the Logical Memory test. Statistical analysis was performed using multiple linear regression models adjusted for age, sex, education, body mass index, smoking status, alcohol consumption and physical activity. Overall, no association was found between the MEDAS score and cognitive tests, which could be explained by the young mean age and high level of education of the participants. Future studies should target young and middle-aged individuals to gain further understanding of the association between Mediterranean diet and cognition in this age group.
Katsoulis M, Stavola BD, Diaz-Ordaz K, et al., 2021, Weight change and the onset of cardiovascular diseases: emulating trials using electronic health records., Epidemiology, Vol: 32, Pages: 744-755, ISSN: 1044-3983
BACKGROUND: Cross-sectional measures of body mass index (BMI) are associated with cardiovascular disease (CVD) incidence, but less is known about whether weight change affects the risk of CVD. METHODS: We estimated the effect of 2-y weight change interventions on 7-y risk of CVD (CVD death, myocardial infarction, stroke, hospitalization from coronary heart disease, and heart failure) by emulating hypothetical interventions using electronic health records. We identified 138,567 individuals with 45-69 years of age without chronic disease in England from 1998 to 2016. We performed pooled logistic regression, using inverse-probability weighting to adjust for baseline and time-varying confounders. We categorized each individual into a weight loss, maintenance, or gain group. RESULTS: Among those of normal weight, both weight loss [risk difference (RD) vs. weight maintenance = 1.5% (0.3% to 3.0%)] and gain [RD = 1.3% (0.5% to 2.2%)] were associated with increased risk for CVD compared with weight maintenance. Among overweight individuals, we observed moderately higher risk of CVD in both the weight loss [RD = 0.7% (-0.2% to 1.7%)] and the weight gain group [RD = 0.7% (-0.1% to 1.7%)], compared with maintenance. In the obese, those losing weight showed lower risk of coronary heart disease [RD = -1.4% (-2.4% to -0.6%)] but not of stroke. When we assumed that chronic disease occurred 1-3 years before the recorded date, estimates for weight loss and gain were attenuated among overweight individuals; estimates for loss were lower among obese individuals. CONCLUSION: Among individuals with obesity, the weight-loss group had a lower risk of coronary heart disease but not of stroke. Weight gain was associated with increased risk of CVD across BMI groups. See video abstract at, http://links.lww.com/EDE/B838.
Tsilidis K, 2021, Prevalence and determinants of sex-specific dietary supplement use in a Greek cohort, Nutrients, Vol: 13, Pages: 1-15, ISSN: 2072-6643
We describe the profile of dietary supplement use and its correlates in the Epirus Health Study cohort, which consists of 1,237 adults (60.5% women) residing in urban north-west Greece. The association between dietary supplement use and demographic characteristics, lifestyle behaviours, personal medical history and clinical measurements was assessed using logistic regression models, separately for women and men. The overall prevalence of dietary supplement use was 31.4%, and it was higher in women (37.3%) compared to men (22.4%; p-value=4.2-08). Based on multivariable logistic regression models, dietary supplement use in women was associated with age (positively until middle-age and slightly negatively afterwards), the presence of a chronic health condition (OR=1.71; 95% CI, 1.18-2.46), lost/removed teeth (OR=0.52; 95% CI, 0.35-0.78) and diastolic blood pressure (OR per 5 mmHg increase=0.84; 95% CI, 0.73-0.96); body mass index and worse general health status were borderline inversely associated. In men, dietary supplement use was positively associated with being employed (OR=2.53; 95% CI, 1.21-5.29). A considerable proportion of our sample used dietary supplements, and the factors associated with it differed between women and men.
Watts EL, Perez-Cornago A, Knuppel A, et al., 2021, Prospective analyses of testosterone and sex hormone-binding globulin with the risk of 19 types of cancer in men and postmenopausal women in UK Biobank, INTERNATIONAL JOURNAL OF CANCER, Vol: 149, Pages: 573-584, ISSN: 0020-7136
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- Citations: 23
Dossus L, Kouloura E, Biessy C, et al., 2021, Prospective analysis of circulating metabolites and endometrial cancer risk, Gynecologic Oncology, Vol: 162, Pages: 475-481, ISSN: 0090-8258
AbstractBackgroundEndometrial cancer is strongly associated with obesity and dysregulation of metabolic factors such as estrogen and insulin signaling are causal risk factors for this malignancy. To identify additional novel metabolic pathways associated with endometrial cancer we performed metabolomic analyses on pre-diagnostic plasma samples from 853 case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC).MethodsA total of 129 metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexoses, and sphingolipids) were measured by liquid chromatography-mass spectrometry. Conditional logistic regression estimated the associations of metabolites with endometrial cancer risk. An analysis focusing on clusters of metabolites using the bootstrap lasso method was also employed.ResultsAfter adjustment for body mass index, sphingomyelin [SM] C18:0 was positively (OR1SD: 1.18, 95% CI: 1.05–1.33), and glycine, serine, and free carnitine (C0) were inversely (OR1SD: 0.89, 95% CI: 0.80–0.99; OR1SD: 0.89, 95% CI: 0.79–1.00 and OR1SD: 0.91, 95% CI: 0.81–1.00, respectively) associated with endometrial cancer risk. Serine, C0 and two sphingomyelins were selected by the lasso method in >90% of the bootstrap samples. The ratio of esterified to free carnitine (OR1SD: 1.14, 95% CI: 1.02–1.28) and that of short chain to free acylcarnitines (OR1SD: 1.12, 95% CI: 1.00–1.25) were positively associated with endometrial cancer risk. Further adjustment for C-peptide or other endometrial cancer risk factors only minimally altered the results.ConclusionThese findings suggest that variation in levels of glycine, serine, SM C18:0 and free carnitine may represent specific pathways linked to endometrial cancer development. If causal, these pathways may offer novel targets for endometrial cancer prevention.
Christakoudi S, Tsilidis K, Evangelou E, et al., 2021, A Body Shape Index (ABSI), hip index and risk of cancer in the UK Biobank cohort, Cancer Medicine, Vol: 10, Pages: 5614-5628, ISSN: 2045-7634
Abdominal size is associated positively with the risk of some cancers but the influence of body mass index (BMI) and gluteofemoral size is unclear because waist and hip circumference are strongly correlated with BMI. We examined associations of 33 cancers with A Body Shape Index (ABSI) and hip index (HI), which are independent of BMI by design, and compared these with waist and hip circumference, using multivariable Cox proportional hazards models in UK Biobank. During a mean follow up of seven years, 14,682 incident cancers were ascertained in 200,289 men and 12,965 cancers in 230,326 women. In men, ABSI was associated positively with cancers of the head and neck (hazard ratio HR=1.14; 95% confidence interval 1.03-1.26 per one standard deviation increment), oesophagus (adenocarcinoma, HR=1.27; 1.12-1.44), gastric cardia (HR=1.31; 1.07-1.61), colon (HR=1.18; 1.10-1.26), rectum (HR=1.13; 1.04-1.22), lung (adenocarcinoma, HR=1.16; 1.03-1.30; squamous-cell carcinoma (SCC), HR=1.33; 1.17-1.52), and bladder (HR=1.15; 1.04-1.27), while HI was associated inversely with cancers of the oesophagus (adenocarcinoma, HR=0.89; 0.79-1.00), gastric cardia (HR=0.79; 0.65-0.96), colon (HR=0.92; 0.86-0.98), liver (HR=0.86; 0.75-0.98), and multiple myeloma (HR=0.86; 0.75-1.00). In women, ABSI was associated positively with cancers of the head and neck (HR=1.27; 1.10-1.48), oesophagus (SCC, HR=1.37; 1.07-1.76), colon (HR=1.08; 1.01-1.16), lung (adenocarcinoma, HR=1.17; 1.06-1.29; SCC, HR=1.40; 1.20-1.63; small-cell, HR=1.39; 1.14-1.69), kidney (clear-cell, HR=1.25; 1.03-1.50), and post-menopausal endometrium (HR=1.11; 1.02-1.20), while HI was associated inversely with skin SCC (HR=0.91; 0.83-0.99), post-menopausal kidney cancer (HR=0.77; 0.67-0.88) and post-menopausal melanoma (HR=0.90; 0.83-0.98). Unusually, ABSI was associated inversely with melanoma in men (HR=0.89; 0.82-0.96) and pre-menopausal women (HR=0.77; 0.65-0.91). Waist and hip circumference reflected associations with BMI
Tsilidis K, 2021, An umbrella review of the evidence associating diet and cancer risk at 11 anatomical sites, Nature Communications, Vol: 12, Pages: 1-10, ISSN: 2041-1723
There is evidence that diet and nutrition are modifiable risk factors for several cancers, but associations may be flawed due to inherent biases. Nutritional epidemiology studies have largely relied on a single assessment of diet using food frequency questionnaires. We conduct an umbrella review of meta-analyses of observational studies to evaluate the strength and validity of the evidence for the association between food/nutrient intake and risk of developing or dying from 11 primary cancers. It is estimated that only few single food/nutrient and cancer associations are supported by strong or highly suggestive meta-analytic evidence, and future similar research is unlikely to change this evidence. Alcohol consumption is positively associated with risk of postmenopausal breast, colorectal, esophageal, head & neck and liver cancer. Consumption of dairy products, milk, calcium and wholegrains are inversely associated with colorectal cancer risk. Coffee consumption is inversely associated with risk of liver cancer and skin basal cell carcinoma.
Ried-Larsen M, Rasmussen MG, Blond K, et al., 2021, Association of cycling with all-cause and cardiovascular disease mortality among persons with diabetes. The European Prospective Investigation into Cancer and Nutrition (EPIC) study, JAMA Internal Medicine, ISSN: 2168-6106
Importance: Premature death from all causes and cardiovascular disease (CVD) causes is higher among persons with diabetes.Objective: To investigate the association between time spent cycling and all-cause and CVD mortality among persons with diabetes, as well as to evaluate the association between change in time spent cycling and risk of all-cause and CVD mortality.Design, Setting, and Participants: This prospective cohort study included 7459 adults with diabetes from the European Prospective Investigation into Cancer and Nutrition study. Questionnaires regarding medical history, sociodemographic, and lifestyle information were administered in 10 Western European countries from 1992 through 2000 (baseline examination) and at a second examination 5 years after baseline. A total of 5423 participants with diabetes completed both examinations. The final updated primary analysis was conducted on November 13, 2020.Exposures: The primary exposure was self-reported time spent cycling per week at the baseline examination. The secondary exposure was change in cycling status from baseline to the second examination.Main Outcomes and Measures The primary and secondary outcomes were all-cause and CVD mortality, respectively, adjusted for other physical activity modalities, diabetes duration, and sociodemographic and lifestyle factors.Results: Of the 7459 adults with diabetes included in the analysis, the mean (SD) age was 55.9 (7.7) years, and 3924 (52.6%) were female. During 110 944 person-years of follow-up, 1673 deaths from all causes were registered. Compared with the reference group of people who reported no cycling at baseline (0 min/wk), the multivariable-adjusted hazard ratios for all-cause mortality were 0.78 (95% CI, 0.61-0.99), 0.76 (95% CI, 0.65-0.88), 0.68 (95% CI, 0.57-0.82), and 0.76 (95% CI, 0.63-0.91) for cycling 1 to 59, 60 to 149, 150 to 299, and 300 or more min/wk, respectively. In an analysis of change in time spent cycling with 57 802 person-years of f
Al-Jafar R, Elliott P, Tsilidis KK, et al., 2021, London Ramadan Fasting Study (LORANS): Rationale, design, and methods
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Hundreds of millions of Muslims fast during the month of Ramadan. The London Ramadan Fasting Study (LORANS) aims to assess the lifestyle changes during this month and investigate the effect of Ramadan fasting on health.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>LORANS is an observational study of participants that follow religious fasting in Ramadan. We advertised, recruited, and visited participants in five mosques in London, United Kingdom. In total, 146 individuals were recruited before Ramadan in May 2019 of which 85 participated in the follow up visit after Ramadan. The study protocol was approved by the ethics committee affiliated to Imperial College London. A written informed consent was signed by all the participants. Every participant completed a questionnaire, a physical examination, and gave blood samples at each visit. Moreover, they completed a 3-day food diary before Ramadan and once again during Ramadan to record dietary changes during the month of fasting.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The mean age of participants was 45.6± 15.9 years. 47.1% of the participants were females, 25.5% were obese, 4.7% were smokers, 14% were diabetic, 24% were hypertensive, and 5.2% had cardiovascular diseases. Data collection covered demographics, lifestyle, food intake, blood pressure, anthropometric measurements, body composition, and metabolic biomarker profiling.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>By engaging with mosques, proper introduction of the study aims and convenient recruitment in the mosque, we were able to recruit a balanced population regarding age and sex and collected valuable data on Ramadan fasting using high-quality
Janiaud P, Agarwal A, Tzoulaki I, et al., 2021, Validity of observational evidence on putative risk and protective factors: appraisal of 3744 meta-analyses on 57 topics, BMC Medicine, Vol: 19, ISSN: 1741-7015
BACKGROUND: The validity of observational studies and their meta-analyses is contested. Here, we aimed to appraise thousands of meta-analyses of observational studies using a pre-specified set of quantitative criteria that assess the significance, amount, consistency, and bias of the evidence. We also aimed to compare results from meta-analyses of observational studies against meta-analyses of randomized controlled trials (RCTs) and Mendelian randomization (MR) studies. METHODS: We retrieved from PubMed (last update, November 19, 2020) umbrella reviews including meta-analyses of observational studies assessing putative risk or protective factors, regardless of the nature of the exposure and health outcome. We extracted information on 7 quantitative criteria that reflect the level of statistical support, the amount of data, the consistency across different studies, and hints pointing to potential bias. These criteria were level of statistical significance (pre-categorized according to 10-6, 0.001, and 0.05 p-value thresholds), sample size, statistical significance for the largest study, 95% prediction intervals, between-study heterogeneity, and the results of tests for small study effects and for excess significance. RESULTS: 3744 associations (in 57 umbrella reviews) assessed by a median number of 7 (interquartile range 4 to 11) observational studies were eligible. Most associations were statistically significant at P < 0.05 (61.1%, 2289/3744). Only 2.6% of associations had P < 10-6, ≥1000 cases (or ≥20,000 participants for continuous factors), P < 0.05 in the largest study, 95% prediction interval excluding the null, and no large between-study heterogeneity, small study effects, or excess significance. Across the 57 topics, large heterogeneity was observed in the proportion of associations fulfilling various quantitative criteria. The quantitative criteria were mostly independent from one another. Across 62 associations assessed in both RCTs and in o
Ioannidou A, Watts E, Perez-Cornago A, et al., 2021, The relationship between Lipoprotein A and other lipids with prostate cancer risk: A multivariable Mendelian randomisation study, Publisher: Cold Spring Harbor Laboratory
Background Numerous epidemiological studies have investigated the role of blood lipids in prostate cancer (PCa) risk though findings remain inconclusive to date. The ongoing research has mainly involved observational studies which are often prone to confounding. This study aimed to identify the relationship between genetically predicted blood lipid concentrations and PCa.Methods and Findings Data for low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides (TG), apolipoprotein A (apoA) and B (apoB), lipoprotein A (Lp(a)) and PCa were acquired from genome-wide association studies in UK Biobank and the PRACTICAL consortium, respectively. We used a two-sample Mendelian randomisation (MR) approach with both univariable and multivariable (MVMR) models and utilised a variety of robust methods and sensitivity analyses to assess the possibility of MR assumptions violation. No association was observed between genetically predicted concentrations of HDL, TG, apoA and apoB and PCa risk. Genetically predicted LDL concentration was positively associated with total PCa in the univariable analysis but adjustment for HDL, TG and Lp(a) led to a null association. Genetically predicted concentration of Lp(a) was associated with higher total PCa risk in the univariable (ORweighted median per sd = 1.091; 95% CI 1.028-1.157; P=0.004) and MVMR analyses after adjustment for the other lipid traits (ORIVW per sd = 1.068; 95% CI 1.005-1.134; P = 0.034). Genetically predicted Lp(a) was also associated with advanced (MVMR ORIVW per sd = 1.078; 95% CI 0.999-1.163; P=0.055) and early age onset PCa (MVMR ORIVW per sd = 1.150; 95% CI 1.015,1.303; P = 0.028). Although multiple estimation methods were utilized to minimize the effect of pleiotropic traits, the presence of any unmeasured pleiotropy cannot be excluded and may limit our findings.Conclusions We observed that genetically predicted Lp(a) concentrations are associated with an increased PCa risk. Fu
Lopez DS, Polychronopoulou E, Tsilidis KK, et al., 2021, Independent and Joint Effects of Testosterone Replacement Therapy and Statins use on the Risk o Prostate Cancer Among White, Black, and Hispanic Men, CANCER PREVENTION RESEARCH, Vol: 14, Pages: 719-728, ISSN: 1940-6207
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Gill D, Zuber V, Dawson J, et al., 2021, Risk factors mediating the effect of body mass index and waist-to-hip ratio on cardiovascular outcomes: Mendelian randomization analysis, International Journal of Obesity, Vol: 45, Pages: 1428-1438, ISSN: 0307-0565
BackgroundHigher body mass index (BMI) and waist-to-hip ratio (WHR) increase the risk of cardiovascular disease, but the extent to which this is mediated by blood pressure, diabetes, lipid traits, and smoking is not fully understood.MethodsUsing consortia and UK Biobank genetic association summary data from 140,595 to 898,130 participants predominantly of European ancestry, Mendelian randomization mediation analysis was performed to investigate the degree to which systolic blood pressure (SBP), diabetes, lipid traits, and smoking mediated an effect of BMI and WHR on the risk of coronary artery disease (CAD), peripheral artery disease (PAD) and stroke.ResultsThe odds ratio of CAD per 1-standard deviation increase in genetically predicted BMI was 1.49 (95% CI 1.39 to 1.60). This attenuated to 1.34 (95% CI 1.24 to 1.45) after adjusting for genetically predicted SBP (proportion mediated 27%, 95% CI 3% to 50%), to 1.27 (95% CI 1.17 to 1.37) after adjusting for genetically predicted diabetes (41% mediated, 95% CI 18% to 63%), to 1.47 (95% CI 1.36 to 1.59) after adjusting for genetically predicted lipids (3% mediated, 95% −23% to 29%), and to 1.46 (95% CI 1.34 to 1.58) after adjusting for genetically predicted smoking (6% mediated, 95% CI −20% to 32%). Adjusting for all the mediators together, the estimate attenuated to 1.14 (95% CI 1.04 to 1.26; 66% mediated, 95% CI 42% to 91%). A similar pattern was observed when considering genetically predicted WHR as the exposure, and PAD or stroke as the outcome.ConclusionsMeasures to reduce obesity will lower the risk of cardiovascular disease primarily by impacting downstream metabolic risk factors, particularly diabetes and hypertension. Reduction of obesity prevalence alongside control and management of its mediators is likely to be most effective for minimizing the burden of obesity.
Diez-Obrero V, Van Duijnhoven F, Kim AE, et al., 2021, Genome-wide gene-calcium interaction in relation to colorectal cancer risk., Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
Papadimitriou N, Hidaka A, Kim A, et al., 2021, Consumption of fruits, vegetables and fiber and risk of colorectal cancer: A gene environment interaction analysis., Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
Laiou E, Rapti I, Schwarzer R, et al., 2021, Review: Nudge interventions to promote healthy diets and physical activity, FOOD POLICY, Vol: 102, ISSN: 0306-9192
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Agudo A, Cayssials V, Bonet C, et al., 2021, Inflammatory potential of the diet & risk of gastric cancer in the European Investigation into Cancer & Nutrition, American Journal of Clinical Nutrition, Vol: 36, Pages: 953-964, ISSN: 1938-3207
The role of chronic inflammation on breast cancer (BC) risk remains unclear beyond as an underlying mechanism of obesity and physical activity. We aimed to evaluate the association between the inflammatory potential of the diet and risk of BC overall, according to menopausal status and tumour subtypes. Within the European Prospective Investigation into Cancer and Nutrition cohort, 318,686 women were followed for 14 years, among whom 13,246 incident BC cases were identified. The inflammatory potential of the diet was characterized by an inflammatory score of the diet (ISD). Multivariable Cox regression models were used to assess the potential effect of the ISD on BC risk by means of hazard ratios (HR) and 95% confidence intervals (CI). ISD was positively associated with BC risk. Each increase of one standard deviation (1-Sd) of the score increased by 4% the risk of BC (HR = 1.04; 95% CI 1.01–1.07). Women in the highest quintile of the ISD (indicating a most pro-inflammatory diet) had a 12% increase in risk compared with those in the lowest quintile (HR = 1.12; 95% CI 1.04–1.21) with a significant trend. The association was strongest among premenopausal women, with an 8% increased risk for 1-Sd increase in the score (HR = 1.08; 95% CI 1.01–1.14). The pattern of the association was quite homogeneous by BC subtypes based on hormone receptor status. There were no significant interactions between ISD and body mass index, physical activity, or alcohol consumption. Women consuming more pro-inflammatory diets as measured by ISD are at increased risk for BC, especially premenopausal women.
Kanellopoulou A, Koskeridis F, Markozannes G, et al., 2021, Awareness, knowledge and trust in the Greek authorities towards COVID-19 pandemic: results from the Epirus Health Study cohort, BMC Public Health, Vol: 21, ISSN: 1471-2458
Background: To assess the level of knowledge and trust in the policy decisions taken regarding the coronavirus disease (COVID-19) pandemic among Epirus Health Study (EHS) participants.Methods: The EHS is an ongoing and deeply-phenotyped prospective cohort study that has recruited 667 participants in northwest Greece until August 31st, 2020. Level of knowledge on coronavirus (SARS-CoV-2) transmission and COVID-19 severity was labeled as poor, moderate or good. Variables assessing knowledge and beliefs towards the pandemic were summarized overall and by sex, age group (25-39, 40-49, 50-59, ≥60 years) and period of report (before the lifting of lockdown measures in Greece: March 30th to May 3rd, and two post-lockdown time periods: May 4th to June 31st, July 1st to August 31st). A hypothesis generating exposure-wide association analysis was conducted to evaluate the associations between 153 agnostically-selected explanatory variables and participants’ knowledge. Correction for multiple comparisons was applied using a false discovery rate (FDR) threshold of 5%.Results: A total of 563 participants (49 years mean age; 60% women) had available information on the standard EHS questionnaire, the clinical and biochemical measurements, and the COVID-19-related questionnaire. Percentages of poor, moderate and good knowledge status regarding COVID-19 were 4.5%, 10.0% and 85.6%, respectively. The majority of participants showed absolute or moderate trust in the Greek health authorities for the management of the epidemic (90.1%), as well as in the Greek Government (84.7%) and the official national sources of information (87.4%). Trust in the authorities was weaker in younger participants and those who joined the study after the lifting of lockdown measures (p-value0.001). None of the factors examined was associated with participants’ level of knowledge after correction for multiple testing.Conclusions: High level of knowledge about the COVID-19 pandemic and t
Tsilidis KK, Papadimitriou N, Dimou N, et al., 2021, Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study, American Journal of Clinical Nutrition, Vol: 113, Pages: 1490-1502, ISSN: 0002-9165
BACKGROUND: The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited. OBJECTIVES: To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR). METHODS: Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions. RESULTS: Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetica
Corlin L, Ruan M, Tsilidis KK, et al., 2021, Two-sample mendelian randomization analysis of associations between periodontal disease and risk of cancer., JNCI Cancer Spectrum, Vol: 5, ISSN: 2515-5091
Background: Observational studies indicate that periodontal disease may increase the risk of colorectal, lung, and pancreatic cancers. Using a 2-sample Mendelian randomization (MR) analysis, we assessed whether a genetic predisposition index for periodontal disease was associated with colorectal, lung, or pancreatic cancer risks. Methods: Our primary instrument included single nucleotide polymorphisms with strong genome-wide association study evidence for associations with chronic, aggressive, and/or severe periodontal disease (rs729876, rs1537415, rs2738058, rs12461706, rs16870060, rs2521634, rs3826782, and rs7762544). We used summary-level genetic data for colorectal cancer (n = 58 131 cases; Genetics and Epidemiology of Colorectal Cancer Consortium, Colon Cancer Family Registry, and Colorectal Transdisciplinary Study), lung cancer (n = 18 082 cases; International Lung Cancer Consortium), and pancreatic cancer (n = 9254 cases; Pancreatic Cancer Consortia). Four MR approaches were employed for this analysis: random-effects inverse-variance weighted (primary analyses), Mendelian Randomization-Pleiotropy RESidual Sum and Outlier, simple median, and weighted median. We conducted secondary analyses to determine if associations varied by cancer subtype (colorectal cancer location, lung cancer histology), sex (colorectal and pancreatic cancers), or smoking history (lung and pancreatic cancer). All statistical tests were 2-sided. Results: The genetic predisposition index for chronic or aggressive periodontitis was statistically significantly associated with a 3% increased risk of colorectal cancer (per unit increase in genetic index of periodontal disease; P = .03), 3% increased risk of colon cancer (P = .02), 4% increased risk of proximal colon cancer (P = .01), and 3% increased risk of colorectal cancer among females (P = .04); however, it was not statistically significantl
Pearson-Stuttard J, Papadimitriou N, Markozannes G, et al., 2021, Type 2 diabetes and cancer: an umbrella review of observational and Mendelian randomisation studies, Cancer Epidemiology, Biomarkers and Prevention, Vol: 30, Pages: 1218-1228, ISSN: 1055-9965
Background Type 2 diabetes(T2DM) has been associated with an increased risk of developing several common cancers, but it is unclear whether this association is causal. We aimed to summarise the evidence on T2DM and cancer and evaluate the validity of associations from both observational and Mendelian randomisation(MR) studies. Methods We performed an umbrella review of the evidence across meta-analyses of observational studies that examined associations of T2DM with risk of developing or dying from site-specific cancers, and MR studies that explored the potential causal association of T2DM and associated biomarkers with cancer risk. Results We identified eligible observational meta-analyses that assessed associations between T2DM and cancer incidence for 18 cancer sites, cancer mortality for seven sites, and cancer incidence or mortality for four sites. Positive associations between T2DM and six cancers reached strong or highly suggestive evidence. We found eight MR studies assessing the association of genetically predicted T2DM and seven and eight studies assessing the association of genetically predicted fasting insulin or fasting glucose concentrations, respectively, upon site-specific cancers. Positive associations were found between genetically predicted T2DM and fasting insulin and risk of six cancers. There was no association between genetically predicted fasting plasma glucose and cancer except for squamous cell lung carcinoma. Conclusions We found robust observational evidence for the association between T2DM and colorectal, hepatocellular, gallbladder, breast, endometrial and pancreatic cancer. Impact Potential causal associations were identified for genetically predicted T2DM and fasting insulin concentrations and risk of endometrial, pancreas, kidney, breast, lung and cervical cancer.
Tsilidis KK, 2021, Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study (vol 113, pg 1490, 2021), AMERICAN JOURNAL OF CLINICAL NUTRITION, Vol: 113, Pages: 1715-1715, ISSN: 0002-9165
Lopez DS, Huang D, Tsilidis KK, et al., 2021, The role of testosterone replacement therapy and statin use, and their combination, in prostate cancer, Cancer Causes and Control, Vol: 32, Pages: 965-976, ISSN: 0957-5243
Purpose:Previous studies have reported conflicting results in the associations of testosterone replacement therapy (TTh) and statins use with prostate cancer (PCa). However, the combination of these treatments with PCa stage and grade at diagnosis and prostate cancer-specific mortality (PCSM) and by race/ethnicity remains unclear.Methods:We identified non-Hispanic White (NHW, N = 58,576), non-Hispanic Black (NHB, n = 9,703) and Hispanic (n = 4,898) men diagnosed with PCa in SEER-Medicare data 2007–2011. Pre-diagnostic prescription of TTh and statins was ascertained for this analysis. Multivariable-adjusted logistic and Cox proportional hazards models were used to evaluate the association of TTh and statins use with PCa stage and grade and PCSM.Results:22.5% used statins alone, 1.2% used TTh alone, and 0.8% used both. TTh and statins were independently, inversely associated with PCa advanced stage and high grade. TTh plus statins was associated with 44% lower odds of advanced stage PCa (OR 0.56, 95% CI 0.35–0.91). As expected, similar inverse associations were present in NHWs as the overall cohort is mostly comprised NHW men. In Hispanic men, statin use with or without TTh was inversely associated with aggressive PCa.Conclusions:Pre-diagnostic use of TTh or statins, independent or in combination, was inversely associated with aggressive PCa, including in NHW and Hispanics men, but was not with PCSM. The findings for use of statins with aggressive PCa are consistent with cohort studies. Future prospective studies are needed to explore the independent inverse association of TTh and the combined inverse association of TTh plus statins on fatal PCa.
Amadou A, Freisling H, Jenab M, et al., 2021, Prevalent diabetes and risk of total, colorectal, prostate and breast cancers in an ageing population: meta-analysis of individual participant data from cohorts of the CHANCES consortium, BRITISH JOURNAL OF CANCER, Vol: 124, Pages: 1882-1890, ISSN: 0007-0920
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