Publications
1312 results found
Yammine SG, Huybrechts I, Biessy C, et al., 2023, Dietary fatty acids and endometrial cancer risk within the European Prospective Investigation into Cancer and Nutrition., BMC Cancer, Vol: 23, Pages: 1-12, ISSN: 1471-2407
BACKGROUND: Diet may impact important risk factors for endometrial cancer such as obesity and inflammation. However, evidence on the role of specific dietary factors is limited. We investigated associations between dietary fatty acids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: This analysis includes 1,886 incident endometrial cancer cases and 297,432 non-cases. All participants were followed up for a mean of 8.8 years. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of endometrial cancer across quintiles of individual fatty acids estimated from various food sources quantified through food frequency questionnaires in the entire EPIC cohort. The false discovery rate (q-values) was computed to control for multiple comparisons. RESULTS: Consumption of n-6 γ-linolenic acid was inversely associated with endometrial cancer risk (HR comparing 5th with 1st quintileQ5-Q1=0.77, 95% CI = 0.64; 0.92, ptrend=0.01, q-value = 0.15). This association was mainly driven by γ-linolenic acid derived from plant sources (HRper unit increment=0.94, 95%CI= (0.90;0.98), p = 0.01) but not from animal sources (HRper unit increment= 1.00, 95%CI = (0.92; 1.07), p = 0.92). In addition, an inverse association was found between consumption of n-3 α-linolenic acid from vegetable sources and endometrial cancer risk (HRper unit increment= 0.93, 95%CI = (0.87; 0.99), p = 0.04). No significant association was found between any other fatty acids (individual or grouped) and endometrial cancer risk. CONCLUSION: Our results suggest that higher consumption of γ-linolenic acid and α-linoleic acid from plant sources may be associated with lower risk of endometrial cancer.
Chan DSM, Vieira R, Abar L, et al., 2023, Postdiagnosis body fatness, weight change and breast cancer prognosis: Global Cancer Update Program (CUP global) systematic literature review and meta-analysis, International Journal of Cancer, Vol: 152, Pages: 572-599, ISSN: 0020-7136
Previous evidence on postdiagnosis body fatness and mortality after breast cancer was graded as limited-suggestive. To evaluate the evidence on body mass index (BMI), waist circumference, waist-hip-ratio and weight change in relation to breast cancer prognosis, an updated systematic review was conducted. PubMed and Embase were searched for relevant studies published up to 31 October, 2021. Random-effects meta-analyses were conducted to estimate summary relative risks (RRs). The evidence was judged by an independent Expert Panel using pre-defined grading criteria. One randomized controlled trial and 225 observational studies were reviewed (220 publications). There was strong evidence (likelihood of causality: probable) that higher postdiagnosis BMI was associated with increased all-cause mortality (64 studies, 32 507 deaths), breast cancer-specific mortality (39 studies, 14 106 deaths) and second primary breast cancer (11 studies, 5248 events). The respective summary RRs and 95% confidence intervals per 5 kg/m2 BMI were 1.07 (1.05-1.10), 1.10 (1.06-1.14) and 1.14 (1.04-1.26), with high between-study heterogeneity (I2 = 56%, 60%, 66%), but generally consistent positive associations. Positive associations were also observed for waist circumference, waist-hip-ratio and all-cause and breast cancer-specific mortality. There was limited-suggestive evidence that postdiagnosis BMI was associated with higher risk of recurrence, nonbreast cancer deaths and cardiovascular deaths. The evidence for postdiagnosis (unexplained) weight or BMI change and all outcomes was graded as limited-no conclusion. The RCT showed potential beneficial effect of intentional weight loss on disease-free-survival, but more intervention trials and well-designed observational studies in diverse populations are needed to elucidate the impact of body composition and their changes on breast cancer outcomes.
Tsilidis KK, Cariolou M, Becerra-Tomas N, et al., 2023, Postdiagnosis body fatness, recreational physical activity, dietary factors and breast cancer prognosis: Global Cancer Update Programme (CUP Global) summary of evidence grading, International Journal of Cancer, Vol: 152, Pages: 635-644, ISSN: 0020-7136
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.
Becerra-Tomas N, Balducci K, Abar L, et al., 2023, Postdiagnosis dietary factors, supplement use and breast cancer prognosis: Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis, International Journal of Cancer, Vol: 152, Pages: 616-634, ISSN: 0020-7136
Little is known about how diet might influence breast cancer prognosis. The current systematic reviews and meta-analyses summarise the evidence on postdiagnosis dietary factors and breast cancer outcomes from randomised controlled trials and longitudinal observational studies. PubMed and Embase were searched through 31st October 2021. Random-effects linear dose-response meta-analysis was conducted when at least three studies with sufficient information were available. The quality of the evidence was evaluated by an independent Expert Panel. We identified 108 publications. No meta-analysis was conducted for dietary patterns, vegetables, wholegrains, fish, meat, and supplements due to few studies, often with insufficient data. Meta-analysis was only possible for all-cause mortality with dairy, isoflavone, carbohydrate, dietary fibre, alcohol intake and serum 25-hydroxyvitamin D (25(OH)D), and for breast cancer-specific mortality with fruit, dairy, carbohydrate, protein, dietary fat, fibre, alcohol intake and serum 25(OH)D. The results, with few exceptions, were generally null. There was limited-suggestive evidence that predefined dietary patterns may reduce the risk of all-cause and other causes of death; that isoflavone intake reduces the risk of all-cause mortality (relative risk (RR) per 2 mg/day: 0.96, 95% confidence interval (CI): 0.92-1.02), breast cancer-specific mortality (RR for high vs low: 0.83, 95% CI: 0.64-1.07), and recurrence (RR for high vs low: 0.75, 95% CI: 0.61-0.92); that dietary fibre intake decreases all-cause mortality (RR per 10 g/day: 0.87, 95% CI: 0.80-0.94); and that serum 25(OH)D is inversely associated with all-cause and breast cancer-specific mortality (RR per 10 nmol/L: 0.93, 95% CI: 0.89-0.97 and 0.94, 95% CI: 0.90-0.99, respectively). The remaining associations were graded as limited-no conclusion.
Cariolou M, Abar L, Aune D, et al., 2023, Postdiagnosis recreational physical activity and breast cancer prognosis: Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis, International Journal of Cancer, Vol: 152, Pages: 600-615, ISSN: 0020-7136
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.
Wong E, Bertin N, Hebrard M, et al., 2023, The Singapore National Precision Medicine Strategy, NATURE GENETICS, Vol: 55, Pages: 178-+, ISSN: 1061-4036
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- Citations: 3
Karavasiloglou N, Hughes DJ, Murphy N, et al., 2023, Prediagnostic serum calcium concentrations and risk of colorectal cancer development in 2 large European prospective cohorts, The American Journal of Clinical Nutrition, Vol: 117, Pages: 33-45, ISSN: 0002-9165
BACKGROUND: Higher dietary calcium consumption is associated with lower colorectal cancer (CRC) risk. However, little data are available on the association between circulating calcium concentrations and CRC risk. OBJECTIVES: To explore the association between circulating calcium concentrations and CRC risk using data from 2 large European prospective cohort studies. METHODS: Conditional logistic regression models were used to calculate multivariable-adjusted ORs and 95% CIs in case-control studies nested within the European Prospective Investigation into Cancer and Nutrition (EPIC; n-cases = 947, n-controls = 947) and the UK Biobank (UK-BB; n-cases = 2759, n-controls = 12,021) cohorts. RESULTS: In EPIC, nonalbumin-adjusted total serum calcium (a proxy of free calcium) was not associated with CRC (OR: 0.94; 95% CI: 0.85, 1.03; modeled as continuous variable, per 1 mg/dL increase), colon cancer (OR: 0.93; 95% CI: 0.82, 1.05) or rectal cancer (OR: 1.01; 95% CI: 0.84, 1.20) risk in the multivariable adjusted model. In the UK-BB, serum ionized calcium (free calcium, most active form) was inversely associated with the risk of CRC (OR: 0.85; 95% CI: 0.76, 0.95; per 1 mg/dL) and colon cancer (OR: 0.78; 95% CI: 0.68, 0.90), but not rectal cancer (OR: 1.02; 95% CI: 0.83, 1.24) in multivariable adjusted models. Meta-analysis of EPIC and UK-BB CRC risk estimates showed an inverse risk association for CRC in the multivariable adjusted model (OR: 0.90; 95%CI: 0.84, 0.97). In analyses by quintiles, in both cohorts, higher levels of serum calcium were associated with reduced CRC risk (EPIC: ORQ5vs.Q1: 0.69; 95% CI: 0.47, 1.00; P-trend = 0.03; UK-BB: ORQ5vs.Q1: 0.82; 95% CI: 0.72, 0.94; P-trend < 0.01). Analyses by anatomical subsite showed an inverse cancer risk association in the colon (EPIC: ORQ5vs.Q1: 0.63, 95% CI: 0.39, 1.02; P-trend = 0.05; UK-BB: ORQ5vs.Q1: 0.75; 95% CI: 0.64, 0.88; P-trend < 0.01) but not the rectum. CONCLUSIONS: In UK-BB, higher serum ionized calcium
Casalone E, Birolo G, Pardini B, et al., 2022, Serum extracellular vesicle-derived microRNAs as potential biomarkers for pleural mesothelioma in a European prospective study, Cancers, Vol: 15, Pages: 1-15, ISSN: 2072-6694
Malignant pleural mesothelioma (MPM) is an aggressive cancer with a dismal prognosis. Early therapeutic interventions could improve patient outcomes. We aimed to identify a pattern of microRNAs (miRNAs) as potential early non-invasive markers of MPM. In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition cohort, we screened the whole miRNome in serum extracellular vesicles (EVs) of preclinical MPM cases. In a subgroup of 20 preclinical samples collected five years prior MPM diagnosis, we observed an upregulation of miR-11400 (fold change (FC) = 2.6, adjusted p-value = 0.01), miR-148a-3p (FC = 1.5, p-value = 0.001), and miR-409-3p (FC = 1.5, p-value = 0.04) relative to matched controls. The 3-miRNA panel showed a good classification capacity with an area under the receiver operating characteristic curve (AUC) of 0.81 (specificity = 0.75, sensitivity = 0.70). The diagnostic ability of the model was also evaluated in an independent retrospective cohort, yielding a higher predictive power (AUC = 0.86). A signature of EV miRNA can be detected up to five years before MPM; moreover, the identified miRNAs could provide functional insights into the molecular changes related to the late carcinogenic process, preceding MPM development.
Leong W-Y, Gupta A, Hasan M, et al., 2022, Reference equations for evaluation of spirometry function tests in South Asia, and amongst South Asians living in other countries, European Respiratory Journal, Vol: 60, ISSN: 0903-1936
Background:There is little data to accurate interpretation of spirometry data in SouthAsia, a major global region with high reported burden for chronicrespiratory disease.Method:We measured lung function in 7,453 healthy men and women aged over18 years, from Bangladesh, North India, South India, Pakistan and SriLanka, as part of the South Asia Biobank study. We first assessed theaccuracy of existing equations for predicting normal forced vital capacity(FVC), forced expiratory volume in 1s (FEV1), and FEV1/FVC ratio. Wethen used our data to derive (N=5,589) and internally validate(N=1,864) new prediction equations amongst South Asians, with furtherexternal validation amongst 339 healthy South Asians living inSingapore.Results:GLI2012 and NHANESIII consistently overestimated expiratory volumes(best fit GLI-SEA, mean [sd] z-score: FEV1 -1.29 [1.04]; FVC -1.12[1.12]). Age, height and weight were strong predictors of lung functionin our participants (P<0.001), and sex specific reference equations usingthese three variables were highly accurate in both internal validation (z-scores: FEV1 0.03 [0.99]; FVC 0.04 [0.97]; FEV1/FVC -0.03 [0.99]) andexternal validation (z-scores: FEV1 0.31 [0.99]; FVC 0.24 [0.97];FEV1/FVC 0.16 [0.91]). Further adjustment for study regions improvesthe model fit, with highest accuracy for estimation of region specific lungfunction in South Asia.Conclusion:We present improved equations for predicting lung function in SouthAsians. These offer the opportunity to enhance diagnosis andmanagement of acute and chronic lung diseases in this major globalpopulation.
Aune D, Markozannes G, Abar L, et al., 2022, Physical activity and health-related quality of life in women with breast cancer: a meta-analysis, JNCI Cancer Spectrum, Vol: 6, Pages: 1-14, ISSN: 2515-5091
Background: Physical activity (PA) is associated with improved health-related quality-of-life (HRQoL) among women with breast cancer; however, uncertainty remains regarding PA types and dose (frequency, duration, intensity) and various HRQoL measures. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to clarify whether specific types and doses of physical activity was related to global and specific domains of HRQoL, as part of the Global Cancer Update Programme, formerly known as the World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project. Methods: PubMed and CENTRAL databases were searched up to August 31, 2019. Weighted mean differences (WMDs) in HRQoL scores were estimated using random effects models. An independent Expert Panel graded the evidence. Results: Seventy-nine RCTs (14,554 breast cancer patients) were included. PA interventions resulted in higher global HRQoL as measured by the Functional Assessment of Cancer Therapy-Breast, WMDs (95% confidence intervals)=5.94 (2.64-9.24, I2=59%, n=12), Functional Assessment of Cancer Therapy-General, 4.53 (1.94-7.13, I2=72%, n=18), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30, 6.78 (2.61-10.95, I2=76.3%, n=17). The likelihood of causality was considered probable that PA improves HRqoL in breast cancer survivors. Effects were weaker for physical function and mental/emotional health. Evidence regarding dose and type of PA remains insufficient for firm conclusions. Conclusion: PA results in improved global HRQoL in breast cancer survivors with weaker effects observed for physical function and mental/emotional health. Additional research is needed to define the impact of types and doses of activity on various domains of HRQoL.
Chan SH, Bylstra Y, Teo JX, et al., 2022, Analysis of clinically relevant variants from ancestrally diverse Asian genomes, Nature Communications, Vol: 13, ISSN: 2041-1723
Asian populations are under-represented in human genomics research. Here, we characterize clinically significant genetic variation in 9051 genomes representing East Asian, South Asian, and severely under-represented Austronesian-speaking Southeast Asian ancestries. We observe disparate genetic risk burden attributable to ancestry-specific recurrent variants and identify individuals with variants specific to ancestries discordant to their self-reported ethnicity, mostly due to cryptic admixture. About 27% of severe recessive disorder genes with appreciable carrier frequencies in Asians are missed by carrier screening panels, and we estimate 0.5% Asian couples at-risk of having an affected child. Prevalence of medically-actionable variant carriers is 3.4% and a further 1.6% harbour variants with potential for pathogenic classification upon additional clinical/experimental evidence. We profile 23 pharmacogenes with high-confidence gene-drug associations and find 22.4% of Asians at-risk of Centers for Disease Control and Prevention Tier 1 genetic conditions concurrently harbour pharmacogenetic variants with actionable phenotypes, highlighting the benefits of pre-emptive pharmacogenomics. Our findings illuminate the diversity in genetic disease epidemiology and opportunities for precision medicine for a large, diverse Asian population.
DeVries AA, Dennis J, Tyrer JP, et al., 2022, Copy Number Variants Are Ovarian Cancer Risk Alleles at Known and Novel Risk Loci, JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, Vol: 114, Pages: 1533-1544, ISSN: 0027-8874
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- Citations: 1
Gaziano L, Sun L, Arnold M, et al., 2022, Mild-to-moderate kidney dysfunction and cardiovascular disease: observational and mendelian randomization analyses., Circulation, Vol: 146, Pages: 1-11, ISSN: 0009-7322
BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderat
Berndt S, Vijai J, Benavente Y, et al., 2022, Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes, LEUKEMIA, ISSN: 0887-6924
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- Citations: 4
Botteri E, Peveri G, Berstad P, et al., 2022, Changes in lifestyle and risk of colorectal cancer in the European prospective investigation into cancer and nutrition., American Journal of Gastroenterology, Vol: 10, Pages: 1-10, ISSN: 0002-9270
INTRODUCTION: We investigated the impact of changes in lifestyle habits on colorectal cancer (CRC) risk in a multi-country European cohort. METHODS: We used baseline and follow-up questionnaire data from the EPIC cohort to assess changes in lifestyle habits and their associations with CRC development. We calculated a healthy lifestyle index (HLI) score based on smoking status, alcohol consumption, body mass index and physical activity collected at the two timepoints. HLI ranged from 0 (most unfavourable) to 16 (most favourable). We estimated the association between HLI changes and CRC risk using Cox regression models and reported hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Among 295,865 participants, 2,799 CRC cases were observed over a median of 7.8 years. Median time between questionnaires was 5.7 years. Each unit increase in HLI from the baseline to the follow-up assessment was associated with a statistically significant 3% lower CRC risk. Among participants in the top tertile at baseline (HLI>11), those in the bottom tertile at follow-up (HLI≤9) had a higher CRC risk (HR 1.34; 95%CI 1.02-1.75) than those remaining in the top tertile. Among individuals in the bottom tertile at baseline, those in the top tertile at follow-up had a lower risk (HR 0.77; 95%CI 0.59-1.00) than those remaining in the bottom tertile. DISCUSSION: Improving adherence to a healthy lifestyle was inversely associated with CRC risk, while worsening adherence was positively associated with CRC risk. These results justify and support recommendations for healthy lifestyle changes and healthy lifestyle maintenance for CRC prevention.
Deschasaux-Tanguy M, Huybrechts I, Julia C, et al., 2022, Food choices characterized by the Nutri-Score nutrient profile and risk of cardiovascular diseases, Publisher: OXFORD UNIV PRESS, ISSN: 1101-1262
Mayen A-L, Viallon V, Botteri E, et al., 2022, A longitudinal evaluation of alcohol intake throughout adulthood and colorectal cancer risk, European Journal of Epidemiology, Vol: 37, Pages: 915-929, ISSN: 0393-2990
BackgroundAlcohol intake is an established risk factor for colorectal cancer (CRC); however, there is limited knowledge on whether changing alcohol drinking habits during adulthood modifies CRC risk.ObjectiveLeveraging longitudinal exposure assessments on alcohol intake at different ages, we examined the relationship between change in alcohol intake and subsequent CRC risk.MethodsWithin the European Prospective Investigation into Cancer and Nutrition, changes in alcohol intake comparing follow-up with baseline assessments were investigated in relation to CRC risk. The analysis included 191,180, participants and 1530 incident CRC cases, with exclusion of the first three years of follow-up to minimize reverse causation. Trajectory profiles of alcohol intake, assessed at ages 20, 30, 40, 50 years, at baseline and during follow-up, were estimated using latent class mixed models and related to CRC risk, including 407,605 participants and 5,008 incident CRC cases.ResultsMean age at baseline was 50.2 years and the follow-up assessment occurred on average 7.1 years later. Compared to stable intake, a 12 g/day increase in alcohol intake during follow-up was positively associated with CRC risk (HR = 1.15, 95%CI 1.04, 1.25), while a 12 g/day reduction was inversely associated with CRC risk (HR = 0.86, 95%CI 0.78, 0.95). Trajectory analysis showed that compared to low alcohol intake, men who increased their alcohol intake from early- to mid- and late-adulthood by up to 30 g/day on average had significantly increased CRC risk (HR = 1.24; 95%CI 1.08, 1.42), while no associations were observed in women. Results were consistent by anatomical subsite.ConclusionsIncreasing alcohol intake during mid-to-late adulthood raised CRC risk, while reduction lowered risk.
Piovani D, Hassan C, Repici A, et al., 2022, Risk of Cancer in Inflammatory Bowel Diseases: Umbrella Review and Reanalysis of Meta-analyses, GASTROENTEROLOGY, Vol: 163, Pages: 671-684, ISSN: 0016-5085
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- Citations: 10
Clasen JL, Heath AK, Van Puyvelde H, et al., 2022, Biomarkers of the transsulfuration pathway and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, International Journal of Cancer, Vol: 151, Pages: 708-716, ISSN: 0020-7136
Previous studies have suggested that components of one-carbon metabolism, particularly circulating vitamin B6, have an etiological role in renal cell carcinoma (RCC). Vitamin B6 is a cofactor in the transsulfuration pathway. We sought to holistically investigate the role of the transsulfuration pathway in RCC risk. We conducted a nested case-control study (455 RCC cases and 455 matched controls) within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Plasma samples from the baseline visit were analyzed for metabolites of the transsulfuration pathway, including pyridoxal 5'-phosphate (PLP, the biologically active form of vitamin B6), homocysteine, serine, cystathionine, and cysteine, in addition to folate. Bayesian conditional logistic regression was used to estimate associations of metabolites with RCC risk as well as interactions with established RCC risk factors. Circulating PLP and cysteine were inversely associated with RCC risk, and these association were not attenuated after adjustment for other transsulfuration metabolites (odds ratio (OR) and 90% credible interval (CrI) per 1 SD increase in log concentration: 0.76 [0.66, 0.87]; 0.81 [0.66, 0.96], respectively). A comparison of joint metabolite profiles suggested substantially greater RCC risk for the profile representative of low overall transsulfuration function compared with high function (OR 2.70 [90% CrI 1.26, 5.70]). We found some statistical evidence of interactions of cysteine with body mass index, and PLP and homocysteine with smoking status, on their associations with RCC risk. In conclusion, we found evidence suggesting that the transsulfuration pathway may play a role in metabolic dysregulation leading to RCC development. This article is protected by copyright. All rights reserved.
Fortuin-de Smidt MC, Sewe MO, Lassale C, et al., 2022, Physical activity attenuates but does not eliminate coronary heart disease risk amongst adults with risk factors: EPIC-CVD case-cohort study, European Journal of Preventive Cardiology, Vol: 29, Pages: 1618-1629, ISSN: 2047-4873
AimsThis study aimed to evaluate the association between physical activity and the incidence of coronary heart disease (CHD) in individuals with and without CHD risk factors.Methods and resultsEPIC-CVD is a case-cohort study of 29 333 participants that included 13 582 incident CHD cases and a randomly selected sub-cohort nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Self-reported physical activity was summarized using the Cambridge physical activity index (inactive, moderately inactive, moderately active, and active). Participants were categorized into sub-groups based on the presence or the absence of the following risk factors: obesity (body mass index ≥30 kg/m2), hypercholesterolaemia (total cholesterol ≥6.2 mmol/L), history of diabetes, hypertension (self-reported or ≥140/90 mmHg), and current smoking. Prentice-weighted Cox regression was used to assess the association between physical activity and incident CHD events (non-fatal and fatal).Compared to inactive participants without the respective CHD risk factor (referent), excess CHD risk was highest in physically inactive and lowest in moderately active participants with CHD risk factors. Corresponding excess CHD risk estimates amongst those with obesity were 47% [95% confidence interval (CI) 32–64%] and 21% (95%CI 2–44%), with hypercholesterolaemia were 80% (95%CI 55–108%) and 48% (95%CI 22–81%), with hypertension were 80% (95%CI 65–96%) and 49% (95%CI 28–74%), with diabetes were 142% (95%CI 63–260%), and 100% (95%CI 32–204%), and amongst smokers were 152% (95%CI 122–186%) and 109% (95%CI 74–150%).ConclusionsIn people with CHD risk factors, moderate physical activity, equivalent to 40 mins of walking per day, attenuates but does not completely offset CHD risk.
Heath AK, Muller DC, van den Brandt PA, et al., 2022, Diet-wide association study of 92 foods and nutrients and lung cancer risk in the European Prospective Investigation into Cancer and Nutrition study and the Netherlands Cohort Study, International Journal of Cancer, Vol: 151, Pages: 1935-1946, ISSN: 0020-7136
Diet-wide association study of 92 foods and nutrients and lung cancer risk in the European Prospective Investigation into Cancer and Nutrition study and the Netherlands Cohort Study
Christakoudi S, Riboli E, Evangelou E, et al., 2022, Associations of body shape phenotypes with sex steroids and their binding proteins in the UK Biobank cohort, Scientific Reports, Vol: 12, ISSN: 2045-2322
Associations of sex steroids and their binding proteins with body shape are unclear, because waist and hip circumference are correlated strongly with body size. We defined body shape using “a body shape index” (ABSI) and hip index (HI), which are independent of weight and height by design, and examined associations in multivariable generalised linear models for the UK Biobank cohort (179,902 men, 207,444 women). Total testosterone was associated inversely with ABSI, especially in men. Free testosterone was lowest for large-ABSI-large-HI (“wide”) and highest for small-ABSI-small-HI (“slim”) in men, but lowest for small-ABSI-large-HI (“pear”) and highest for large-ABSI-small-HI (“apple”) in women. Oestradiol was associated inversely with ABSI in obese pre-menopausal women but positively with HI in obese men and post-menopausal women not using hormone replacement therapy. Sex-hormone binding globulin (SHBG) was associated inversely with ABSI but positively with HI and was lowest for “apple” and highest for “pear” phenotype in both sexes. Albumin was associated inversely with HI in women, but matched the pattern of free testosterone in obese men (lowest for “wide”, highest for “slim” phenotype). In conclusion, sex steroids and their binding proteins are associated with body shape, including hip as well as waist size, independent of body size.
Dam V, Onland-Moret NC, Burgess S, et al., 2022, Genetically Determined Reproductive Aging and Coronary Heart Disease: A Bidirectional 2-sample Mendelian Randomization, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 107, Pages: E2952-E2961, ISSN: 0021-972X
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- Citations: 11
Christakoudi S, Riboli E, Evangelou E, et al., 2022, Associations of body shape index (ABSI) and hip index with liver, metabolic, and inflammatory biomarkers in the UK Biobank cohort, Scientific Reports, Vol: 12, ISSN: 2045-2322
Associations of liver, metabolic, and inflammatory biomarkers in blood with body shape are unclear, because waist circumference (WC) and hip circumference (HC) are dependent on overall body size, resulting in bias. We have used the allometric “a body shape index” (ABSI = WC(mm)∗Weight(kg)-2/3∗Height(m)5/6) and hip index (HIwomen = HC(cm)∗Weight(kg)-0.482∗Height(cm)0.310, HImen = HC(cm)∗Weight(kg)-2/5∗Height(cm)1/5), which are independent of body mass index (BMI) by design, in multivariable linear regression models for 121,879 UK Biobank men and 135,559 women. Glucose, glycated haemoglobin (HbA1c), triglycerides, low-density-lipoprotein cholesterol, apolipoprotein-B, alanine aminotransferase (ALT), gamma-glutamyltransferase, and lymphocytes were associated positively with BMI and ABSI but inversely with HI. High-density-lipoprotein cholesterol and apolipoprotein-A1 were associated inversely with BMI and ABSI but positively with HI. Lipid-related biomarkers and ALT were associated only with HI in obese men. C-reactive protein, neutrophils, monocytes, and alkaline phosphatase were associated positively, while bilirubin was associated inversely, with BMI and ABSI but not with HI. Associations were consistent within the clinical reference ranges but were lost or changed direction for low or high biomarker levels. Our study confirms associations with waist and hip size, independent of BMI, for metabolic biomarkers but only with waist size for inflammatory biomarkers, suggesting different contribution of the mechanistic pathways related to body shape.
Chan SSM, Chen Y, Casey K, et al., 2022, Obesity is associated with increased risk of Crohn's disease, but not ulcerative colitis: a pooled analysis of five prospective cohort studies, Clinical Gastroenterology and Hepatology, Vol: 20, Pages: 1048-1058, ISSN: 1542-3565
BACKGROUND AND AIMS: It is unclear whether obesity is associated with the development of inflammatory bowel disease despite compelling data from basic science studies. We therefore examined the association between obesity and risk of Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We conducted pooled analyses of 5 prospective cohorts with validated anthropometric measurements for body mass index (BMI) and waist-hip ratio and other lifestyle factors. Diagnoses of CD and UC were confirmed through medical records or ascertained using validated definitions. We used Cox proportional hazards modeling to calculate pooled multivariable-adjusted HRs (aHRs) and 95% confidence intervals (CIs). RESULTS: Among 601,009 participants (age range, 18-98 years) with 10,110,018 person-years of follow-up, we confirmed 563 incident cases of CD and 1047 incident cases of UC. Obesity (baseline BMI ≥30 kg/m2) was associated with an increased risk of CD (pooled aHR, 1.34; 95% CI, 1.05-1.71, I2 = 0%) compared with normal BMI (18.5 to <25 kg/m2). Each 5 kg/m2 increment in baseline BMI was associated with a 16% increase in risk of CD (pooled aHR, 1.16; 95% CI, 1.05-1.22; I2 = 0%). Similarly, with each 5 kg/m2 increment in early adulthood BMI (age, 18-20 years), there was a 22% increase in risk of CD (pooled aHR, 1.22; 95% CI, 1.05-1.40; I2 = 13.6%). An increase in waist-hip ratio was associated with an increased risk of CD that did not reach statistical significance (pooled aHR across quartiles, 1.08; 95% CI, 0.97-1.19; I2 = 0%). No associations were observed between measures of obesity and risk of UC. CONCLUSIONS: In an adult population, obesity as measured by BMI was associated with an increased risk of older-onset CD but not UC.
Aguenaou H, Babio N, Deschasaux-Tanguy M, et al., 2022, Comment on Muzzioli et al. Are Front-of-Pack Labels a Health Policy Tool? <i>Nutrients</i> 2022, <i>14</i>, 771 <i>Comment</i>, NUTRIENTS, Vol: 14
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- Citations: 2
Mariosa D, Smith-Byrne K, Richardson TG, et al., 2022, Body size at different ages and risk of six cancers: a Mendelian randomization and prospective cohort study, JNCI: Journal of the National Cancer Institute, Vol: 114, Pages: 1296-1300, ISSN: 0027-8874
It is unclear if body weight in early life affects cancer risk independently of adult body weight. To investigate this question for six obesity-related cancers, we performed univariable and multivariable analyses using i) Mendelian randomization (MR) analysis and ii) longitudinal analyses in prospective cohorts. Both the MR and longitudinal analyses indicated that larger body size at age 10 was associated with higher risk of endometrial (ORMR=1.61, 95%CI = 1.23–2.11) and kidney cancer (ORMR=1.40, 95%CI = 1.09–1.80). These associations were attenuated after accounting for adult body size in both the MR and cohort analyses. Early life BMI was not consistently associated with the other investigated cancers. The lack of clear independent risk associations suggests that early life BMI influences endometrial and kidney cancer risk mainly through pathways that are common with adult BMI.
Demirkan A, Zudina L, Pupko I, et al., 2022, Diabetes-cancer multi-phenotype GWAS in EPIC study: an improved power for defining genetic causes of multi-morbidity, Publisher: SPRINGERNATURE, Pages: 494-494, ISSN: 1018-4813
Balkhiyarova Z, Demirkan A, Pupko I, et al., 2022, Blood metabolite levels have shared genetic effects and affect risk of breast and colorectal cancer, Publisher: KARGER, Pages: 33-33, ISSN: 0001-5652
Papadimitriou N, Bouras E, van den Brandt PA, et al., 2022, A prospective diet-wide association study for risk of colorectal cancer in EPIC, Clinical Gastroenterology and Hepatology, Vol: 20, Pages: 864-873.e13, ISSN: 1542-3565
BACKGROUND & AIMS: Evidence regarding the association of dietary exposures with colorectal cancer (CRC) risk is not consistent with a few exceptions. Therefore, we conducted a diet-wide association study (DWAS) in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the associations between several dietary exposures with CRC risk. METHODS: The association of 92 food and nutrient intakes with CRC risk was assessed in 386,792 participants, 5,069 of whom developed incident CRC. Correction for multiple comparisons was performed using the false discovery rate, and emerging associations were examined in the Netherlands Cohort Study (NLCS). Multiplicative gene-nutrient interactions were also tested in EPIC based on known CRC-associated loci. RESULTS: In EPIC, alcohol, liquor/spirits, wine, beer/cider, soft drinks, and pork were positively associated with CRC, whereas milk, cheese, calcium, phosphorus, magnesium, potassium, riboflavin, vitamin B6, beta-carotene, fruit, fibre, non-white bread, banana, and total protein intakes were inversely associated. Of these 20 associations, 13 were replicated in NLCS, for which a meta-analysis was performed, namely alcohol (summary HR per 1 SD increment in intake: 1.07; 95%CI:1.04-1.09), liquor/spirits (1.04; 1.02-1.06), wine (1.04;1.02-1.07), beer/cider (1.06;1.04-1.08), milk (0.95;0.93-0.98), cheese (0.96;0.94-0.99), calcium (0.93;0.90-0.95), phosphorus (0.92;0.90-0.95), magnesium (0.95;0.92-0.98), potassium (0.96;0.94-0.99), riboflavin (0.94;0.92-0.97), beta-carotene (0.96;0.93-0.98), and total protein (0.94;0.92-0.97). None of the gene-nutrient interactions were significant after adjustment for multiple comparisons. CONCLUSIONS: Our findings confirm a positive association for alcohol and an inverse association for dairy products and calcium with CRC risk, and also suggest a lower risk at higher dietary intakes of phosphorus, magnesium, potassium, riboflavin, beta-carotene and total protein.
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