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1.
Vitamin D and human health: evidence from Mendelian randomization studies.
Fang, A, Zhao, Y, Yang, P, Zhang, X, Giovannucci, EL
European journal of epidemiology. 2024
Abstract
We summarized the current evidence on vitamin D and major health outcomes from Mendelian randomization (MR) studies. PubMed and Embase were searched for original MR studies on vitamin D in relation to any health outcome from inception to September 1, 2022. Nonlinear MR findings were excluded due to concerns about the validity of the statistical methods used. A meta-analysis was preformed to synthesize study-specific estimates after excluding overlapping samples, where applicable. The methodological quality of the included studies was evaluated according to the STROBE-MR checklist. A total of 133 MR publications were eligible for inclusion in the analyses. The causal association between vitamin D status and 275 individual outcomes was examined. Linear MR analyses showed genetically high 25-hydroxyvitamin D (25(OH)D) concentrations were associated with reduced risk of multiple sclerosis incidence and relapse, non-infectious uveitis and scleritis, psoriasis, femur fracture, leg fracture, amyotrophic lateral sclerosis, anorexia nervosa, delirium, heart failure, ovarian cancer, non-alcoholic fatty liver disease, dyslipidemia, and bacterial pneumonia, but increased risk of Behçet's disease, Graves' disease, kidney stone disease, fracture of radium/ulna, basal cell carcinoma, and overall cataracts. Stratified analyses showed that the inverse association between genetically predisposed 25(OH)D concentrations and multiple sclerosis risk was significant and consistent regardless of the genetic instruments GIs selected. However, the associations with most of the other outcomes were only pronounced when using genetic variants not limited to those in the vitamin D pathway as GIs. The methodological quality of the included MR studies was substantially heterogeneous. Current evidence from linear MR studies strongly supports a causal role of vitamin D in the development of multiple sclerosis. Suggestive support for a number of other health conditions could help prioritize conditions where vitamin D may be beneficial or harmful.
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Ultra-processed foods and health: a comprehensive review.
Zhang, Y, Giovannucci, EL
Critical reviews in food science and nutrition. 2023;(31):10836-10848
Abstract
Dramatically increasing trends in consumption of ultra-processed foods have been reported across the globe. Public concern about the health consequences of ultra-processed foods is high. This manuscript provides a comprehensive review of trends in global consumption of ultra-processed foods, dietary nutrient profile of ultra-processed foods, demographic, socioeconomic, psychological, and behavioral characteristics of ultra-processed food consumers, current evidence from longitudinal studies at the population level on the association between ultra-processed foods consumption and major health outcomes (including all-cause and cause-specific mortality, cardiovascular disease, overweight and obesity, body composition and fat deposition, diabetes, cancer, and gastrointestinal and other diseases), potential mechanisms linking ultra-processed foods with these outcomes (nutrient displacement, factors that influence adiposity, and processing), and challenges and future research directions. The global trends in consumption of ultra-processed foods, the generally unfavorable nutrient profile of ultra-processed foods, the characteristics of ultra-processed food consumers, the accumulating longitudinal studies associating ultra-processed foods with major health outcomes, and the uncertainties and complexities in putative mechanisms all highlight the need for future high-quality epidemiologic and mechanistic investigations on this topic. It is critical to interpret findings in the light of the totality of evidence.
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3.
Are exposure-disease relationships assessed in cohorts of health professionals generalizable?: a comparative analysis based on WCRF/AICR systematic literature reviews.
Wang, P, Giovannucci, EL
Cancer causes & control : CCC. 2023;(1):39-45
Abstract
PURPOSE Although cohorts of health professionals are not representative of the general US population, the generalizability of exposure-disease relationships identified in these cohorts has not been extensively evaluated. Our objective was to compare the associations of risk factors with cancer risk obtained in the Nurses' Health Study (NHS), Nurses' Health Study II (NHSII), and the Health Professionals Follow-Up Study (HPFS) with those from meta-analyses of cohort studies. METHODS Data were extracted from the most recent systematic literature reviews conducted by the World Cancer Fund/American Institute of Cancer Research (WCRF/AICR). We examined risk factors with "convincing," "probable," or "limited-suggestive" evidence for 17 cancer types. Cohort-specific results for NHS, NHSII, and HPFS and corresponding sex-specific pooled meta-analysis results were obtained when available. We compared associations for continuous variables and inspected potential non-linearity in the dose-response meta-analyses. RESULTS Data for 88 comparisons across 11 cancer types were available. For most risk factors, we observed a close resemblance between the cohort-specific and corresponding sex-specific pooled associations. The 45 comparisons for factors considered as "convincing" or "probable" invariably exhibited similar associations in direction and magnitude. In 44 of the 45, the 95% CI from the NHS, NHSII, or HPFS captured the pooled estimate. In the one exception, the difference was 0.01. CONCLUSION The NHS, NHSII, and HPFS studies are not representative of the general US population concerning sociodemographic and behavioral factors. However, the generalizability of the exposure-disease relationship assessed in these cohorts is not impaired by these factors.
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Postdiagnosis body fatness, recreational physical activity, dietary factors and breast cancer prognosis: Global Cancer Update Programme (CUP Global) summary of evidence grading.
Tsilidis, KK, Cariolou, M, Becerra-Tomás, N, Balducci, K, Vieira, R, Abar, L, Aune, D, Markozannes, G, Nanu, N, Greenwood, DC, et al
International journal of cancer. 2023;(4):635-644
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Abstract
Based on the Global Cancer Update Programme, formally known as the World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project, we performed systematic reviews and meta-analyses to investigate the association of postdiagnosis body fatness, physical activity and dietary factors with breast cancer prognosis. We searched PubMed and Embase for randomised controlled trials and longitudinal observational studies from inception to 31 October 2021. We calculated summary relative risks (RRs) and 95% confidence intervals (CIs) using random-effects meta-analyses. An independent Expert Panel graded the quality of evidence according to predefined criteria. The evidence on postdiagnosis body fatness and higher all-cause mortality (RR per 5 kg/m2 in body mass index: 1.07, 95% CI: 1.05-1.10), breast cancer-specific mortality (RR: 1.10, 95% CI: 1.06-1.14) and second primary breast cancer (RR: 1.14, 95% CI: 1.04-1.26) was graded as strong (likelihood of causality: probable). The evidence for body fatness and breast cancer recurrence and other nonbreast cancer-related mortality was graded as limited (likelihood of causality: limited-suggestive). The evidence on recreational physical activity and lower risk of all-cause (RR per 10 metabolic equivalent of task-hour/week: 0.85, 95% CI: 0.78-0.92) and breast cancer-specific mortality (RR: 0.86, 95% CI: 0.77-0.96) was judged as limited-suggestive. Data on dietary factors was limited, and no conclusions could be reached except for healthy dietary patterns, isoflavone and dietary fibre intake and serum 25(OH)D concentrations that were graded with limited-suggestive evidence for lower risk of the examined outcomes. Our results encourage the development of lifestyle recommendations for breast cancer patients to avoid obesity and be physically active.
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Artificially Sweetened Beverages and Health Outcomes: An Umbrella Review.
Diaz, C, Rezende, LFM, Sabag, A, Lee, DH, Ferrari, G, Giovannucci, EL, Rey-Lopez, JP
Advances in nutrition (Bethesda, Md.). 2023;(4):710-717
Abstract
The consumption of artificially sweetened beverages (ASBs) is increasing in some countries. However, some meta-analyses have found that habitual consumers of ASBs (compared with low or no consumption) had an increased risk on some health outcomes. We performed an umbrella review of meta-analyses to grade the credibility of the evidence of claimed observational associations between ASBs and health outcomes. Data were searched in Web of Science, Embase, and PubMed for systematic reviews published up to 25 May 2022, examining association between ASBs and any health outcomes. Certainty of the evidence for each health outcome was obtained based on statistical results of tests used in umbrella reviews. The AMSTAR-2 tool (16 items) was used to identify high-quality systematic reviews. Answers of each item were rated as yes, no, or partial yes (for a partial adherence to the standard). We included data from 11 meta-analyses with unique population, exposure, comparison group, outcome obtained from 7 systematic reviews (51 cohort studies and 4 case-control studies). ASBs were associated with higher risk of obesity, type 2 diabetes, all-cause mortality, hypertension, and cardiovascular disease incidence (supported by highly suggestive evidence). Evidence for other outcomes (colorectal cancer, pancreatic cancer, gastrointestinal cancer, cancer mortality, cardiovascular mortality, chronic kidney disease, coronary artery disease, and stroke) was weak. Results of the quality assessment of systematic reviews using AMSTAR-2 showed some notable deficiencies: unclear sources of funding of eligible studies and lack of predefined study protocols to guide authors. The consumption of ASBs was associated with a higher risk of obesity, type 2 diabetes, all-cause mortality, hypertension, and cardiovascular disease incidence. However, further cohort studies and clinical trials in humans are still needed to understand the impact of ASBs on health outcomes.
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Field Synopsis of Environmental and Genetic Risk Factors of Sporadic Early-Onset Colorectal Cancer and Advanced Adenoma.
Zhang, R, Boakye, D, Yang, N, Zhou, X, Zhou, Y, Jiang, F, Yu, L, Wang, L, Sun, J, Yuan, S, et al
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2023;(8):1048-1060
Abstract
BACKGROUND To systematically appraise and synthesize available epidemiologic evidence on the associations of environmental and genetic factors with the risk of sporadic early-onset colorectal cancer (EOCRC) and early-onset advanced colorectal adenoma (EOCRA). METHODS Multiple databases were comprehensively searched to identify eligible observational studies. Genotype data from UK Biobank were incorporated to examine their associations with EOCRC in a nested case-control design. Meta-analyses of environmental risk factors were performed, and the strength of evidence was graded based on predefined criteria. Meta-analyses of genetic associations were conducted using the allelic, recessive, and dominant models, respectively. RESULTS A total of 61 studies were included, reporting 120 environmental factors and 62 genetic variants. We found 12 risk factors (current overweight, overweight in adolescence, high waist circumference, smoking, alcohol, sugary beverages intake, sedentary behavior, red meat intake, family history of colorectal cancer, hypertension, hyperlipidemia, and metabolic syndrome) and three protective factors (vitamin D, folate, and calcium intake) for EOCRC or EOCRA. No significant associations between the examined genetic variants and EOCRC risk were observed. CONCLUSIONS Recent data indicate that the changing patterns of traditional colorectal cancer risk factors may explain the rising incidence of EOCRC. However, research on novel risk factors for EOCRC is limited; therefore, we cannot rule out the possibility of EOCRC having different risk factors than late-onset colorectal cancer (LOCRC). IMPACT The potential for the identified risk factors to enhance the identification of at-risk groups for personalized EOCRC screening and prevention and for the prediction of EOCRC risk should be comprehensively addressed by future studies.
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Postdiagnosis recreational physical activity and breast cancer prognosis: Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis.
Cariolou, M, Abar, L, Aune, D, Balducci, K, Becerra-Tomás, N, Greenwood, DC, Markozannes, G, Nanu, N, Vieira, R, Giovannucci, EL, et al
International journal of cancer. 2023;(4):600-615
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Abstract
It is important to clarify the associations between modifiable lifestyle factors such as physical activity and breast cancer prognosis to enable the development of evidence-based survivorship recommendations. We performed a systematic review and meta-analyses to summarise the evidence on the relationship between postbreast cancer diagnosis physical activity and mortality, recurrence and second primary cancers. We searched PubMed and Embase through 31st October 2021 and included 20 observational studies and three follow-up observational analyses of patients enrolled in clinical trials. In linear dose-response meta-analysis of the observational studies, each 10-unit increase in metabolic equivalent of task (MET)-h/week higher recreational physical activity was associated with 15% and 14% lower risk of all-cause (95% confidence interval [CI]: 8%-22%, studies = 12, deaths = 3670) and breast cancer-specific mortality (95% CI: 4%-23%, studies = 11, deaths = 1632), respectively. Recreational physical activity was not associated with breast cancer recurrence (HR = 0.97, 95% CI: 0.91-1.05, studies = 6, deaths = 1705). Nonlinear dose-response meta-analyses indicated 48% lower all-cause and 38% lower breast cancer-specific mortality with increasing recreational physical activity up to 20 MET-h/week, but little further reduction in risk at higher levels. Predefined subgroup analyses across strata of body mass index, hormone receptors, adjustment for confounders, number of deaths, menopause and physical activity intensities were consistent in direction and magnitude to the main analyses. Considering the methodological limitations of the included studies, the independent Expert Panel concluded 'limited-suggestive' likelihood of causality for an association between recreational physical activity and lower risk of all-cause and breast cancer-specific mortality.
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Association of gallstone disease with risk of colorectal cancer: a systematic review and meta-analysis of observational studies.
Polychronidis, G, Siddiqi, H, Ali Ahmed, F, Papatheodorou, S, Giovannucci, EL, Song, M
International journal of epidemiology. 2023;(5):1424-1434
Abstract
BACKGROUND Numerous studies have assessed the association of gallstones or cholecystectomy (CE) with risk of colorectal cancer (CRC). However, the findings are mixed. OBJECTIVE To systematically review and meta-analyse the association between the presence of gallstone disease (GD), or CE and the incidence of CRC. Secondary endpoints were the risk based on type of exposure, study design, tumour subsites and sex. METHODS PubMed and EMBASE were searched from September 2020 to May 2021. The protocol was registered on the Open Science Foundation Platform. We identified and classified studies according to their design into prospective cohort, population-based case-control, hospital-based case-control and necropsy studies reporting CRC incidence among individuals with diagnosed GD or after CE (or both). Among 2157 retrieved studies, 65 (3%) met the inclusion criteria. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Data were extracted by two independent reviewers. We evaluated the quality of the study according to the Newcastle-Ottawa Scale and only studies with a score of 6 and above were included in the final analyses. We pooled log-transformed odds ratios/risk ratios from the available adjusted models to estimate a summary relative risk (RR) and 95% confidence interval (CI) in a random-effects model. The primary outcome was overall CRC incidence. We also conducted secondary analyses according to sex and CRC subsites (proximal colon, distal colon and rectum). The outcome was measured by RRs with 95% CIs. RESULTS The overall association of GD and/or CE with CRC was RR = 1.15 (1.08; 1.24), primarily driven by hospital-based case-control studies [RR = 1.61 (1.29; 2.01)], whereas a more modest association was found in population-based case-control and cohort studies [RR = 1.10 (1.02; 1.19)]. Most hospital-based case-control and necropsy studies reported estimates that were adjusted for age and sex only, leaving room for residual confounding; therefore we restricted to population-based case-control and cohort studies for our subsequent analyses. Similar associations were found for women [RR = 1.21 (1.05; 1.4) and men (RR = 1.24 (1.06; 1.44)]. When assessed by CRC subsites, GD and CE were primarily associated with higher risk of proximal colon cancer [RR = 1.16 (1.07; 1.26)] but not distal colon cancer [RR = 0.99 (0.96; 1.03)] or rectal cancer [RR = 0.94 (0.89; 1.00)]. CONCLUSIONS Gallstones are associated with a modestly increased risk of colon cancer, primarily in the proximal colon.
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Overall and abdominal obesity and risks of all-cause and cause-specific mortality in Korean adults: a pooled analysis of three population-based prospective cohorts.
Jang, H, Kim, R, Lee, JT, Lee, DH, Giovannucci, EL, Oh, H
International journal of epidemiology. 2023;(4):1060-1073
Abstract
BACKGROUND Studies found a J-shaped association between body mass index (BMI) and mortality. However, it is unclear whether the association is driven by biases, particularly confounding by fat-free mass. METHODS We conducted an individual-level pooled analysis of three cohorts of Korean adults (aged ≥ 40 years; n = 153 248). Mortality was followed up through December 2019. Anthropometric data were directly measured at baseline. Fat and fat-free mass were predicted using validated prediction models. Using Cox proportional hazards models, we estimated the associations of BMI and waist circumference (WC) with all-cause and cause-specific mortality. To account for biases, we excluded participants aged ≥ 70 years, deaths that occurred within 5 years of follow-up and ever smokers, and adjusted for fat-free mass index (FFMI). RESULTS During the follow-up of up to 18 years, 6061 deaths were identified. We observed J-shaped association of BMI (nadir at 22-26) and monotonically positive association of WC with all-cause, cardiovascular, and cancer mortality among Korean adults without a history of cancer or cardiovascular disease. In the BMI analysis, excluding ever smokers and adjusting for FFMI attenuated the excess mortality in underweight participants and transformed the J-shaped association into a monotonically positive shape, suggesting an increased mortality at BMI > 22.0. Excluding participants aged ≥ 70 years and deaths that occurred within 5 years of follow-up did not change the results. In the WC analysis, the monotonic positive associations did not change after the control. Similar results were observed among participants with a history of cancer or cardiovascular disease. CONCLUSIONS Our data suggest that both overall and abdominal body fat are associated with increased mortality in Korean adults.
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The Contribution of Genetic Risk and Lifestyle Factors in the Development of Adult-Onset Inflammatory Bowel Disease: A Prospective Cohort Study.
Sun, Y, Yuan, S, Chen, X, Sun, J, Kalla, R, Yu, L, Wang, L, Zhou, X, Kong, X, Hesketh, T, et al
The American journal of gastroenterology. 2023;(3):511-522
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Abstract
INTRODUCTION The joint associations across genetic risk, modifiable lifestyle factors, and inflammatory bowel disease (IBD) remains unclear. METHODS Genetic susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) was estimated by polygenic risk scores and further categorized into high, intermediate, and low genetic risk categories. Weighted healthy lifestyle scores were constructed based on 5 common lifestyle factors and categorized into favorable (4 or 5 healthy lifestyle factors), intermediate (3 healthy lifestyle factors), and unfavorable (0-2 healthy lifestyle factors) groups. Cox proportional hazards regression model was used to estimate the hazard ratios (HR) and 95% confidence interval (CI) for their associations. RESULTS During the 12-year follow-up, 707 cases with CD and 1576 cases with UC were diagnosed in the UK Biobank cohort. Genetic risk and unhealthy lifestyle categories were monotonically associated with CD and UC risk with no multiplicative interaction between them. The HR of CD and UC were 2.24 (95% CI 1.75-2.86) and 2.15 (95% CI 1.82-2.53) for those with a high genetic risk, respectively. The HR of CD and UC for individuals with an unfavorable lifestyle were 1.94 (95% CI 1.61-2.33) and 1.98 (95% CI 1.73-2.27), respectively. The HR of individuals with a high genetic risk but a favorable lifestyle (2.33, 95% CI 1.58-3.44 for CD, and 2.05, 95% CI 1.58-2.66 for UC) were reduced nearly by half, compared with those with a high genetic risk but an unfavorable lifestyle (4.40, 95% CI 2.91-6.66 for CD and 4.44, 95% CI 3.34-5.91 for UC). DISCUSSION Genetic and lifestyle factors were independently associated with susceptibility to incident CD and UC. Adherence to a favorable lifestyle was associated with a nearly 50% lower risk of CD and UC among participants at a high genetic risk.