Intake of dairy products has been associated with risk of some cancers, but findings are often inconsistent and information on hepatocellular carcinoma (HCC) risk is limited, particularly from ...prospective settings. The aim of our study was to investigate the association between consumption of total and specific dairy products (milk/cheese/yogurt) and their components (calcium/vitamin D/fats/protein), with first incident HCC (Ncases = 191) in the European Prospective Investigation into Cancer and Nutrition cohort, including a nested case–control subset (Ncases = 122) with the assessment of hepatitis B virus/hepatitis C virus infections status, liver damage and circulating insulin‐like growth factor (IGF)‐I levels. For cohort analyses, multivariable‐adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI). For nested case–control analyses, conditional logistic regression was used to calculate odds ratios and 95% CI. A total of 477,206 participants were followed‐up for an average of 11 years (person‐years follow‐up = 5,415,385). In the cohort study, a significant positive HCC risk association was observed for total dairy products (highest vs. lowest tertile, HR = 1.66, 95% CI: 1.13–2.43; ptrend = 0.012), milk (HR = 1.51, 95% CI: 1.02–2.24; ptrend = 0.049), and cheese (HR = 1.56, 95% CI: 1.02–2.38; ptrend = 0.101), but not yogurt (HR = 0.94, 95% CI: 0.65–1.35). Dietary calcium, vitamin D, fat and protein from dairy sources were associated with increased HCC risk, whereas the same nutrients from nondairy sources showed inverse or null associations. In the nested case–control study, similar results were observed among hepatitis‐free individuals. Results from this large prospective cohort study suggest that higher consumption of dairy products, particularly milk and cheese, may be associated with increased HCC risk. Validation of these findings in other populations is necessary. Potential biologic mechanisms require further exploration.
What's New?
Currently, the role of dairy product intake in the development of hepatocellular carcinoma (HCC) is unclear. Using detailed data from a large multi‐centric prospective cohort, this study investigated the association between consumption of total and specific dairy products with first incident HCC. The study found that higher dairy product consumption, particularly milk and cheese, was associated with increased HCC risk. Dietary calcium, vitamin D, fat and protein did not explain the observed associations. However, higher circulating IGF‐I levels may play a role.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
MicroRNAs (miRNAs) are post‐transcriptional gene regulators involved in a wide range of biological processes including tumorigenesis. Deregulation of miRNA pathways has been associated with cancer ...but the contribution of their genetic variability to this disorder is poorly known. We analyzed the genetic association of gastric cancer (GC) and its anatomical and histological subtypes, with 133 single‐nucleotide polymorphisms (SNPs) tagging 15 isolated miRNAs and 24 miRNA clusters potentially involved in cancer, in 365 GC cases and 1,284 matched controls within the European Prospective Investigation into Cancer and Nutrition cohort. Various SNPs were associated with GC under the log‐additive model. Furthermore, several of these miRNAs passed the gene‐based permutation test when analyzed according to GC subtypes: three tagSNPs of the miR‐29a/miR‐29b‐1 cluster were associated with diffuse subtype (minimum p‐value = 1.7 × 10−4; odds ratio, OR = 1.72; 95% confidence interval, CI = 1.30–2.28), two tagSNPs of the miR‐25/miR‐93/miR‐106b cluster were associated with cardia GC (minimum p‐value = 5.38 × 10−3; OR = 0.56, 95% CI = 0.37–0.86) and one tagSNP of the miR‐363/miR‐92a‐2/miR‐19b‐2/miR‐20b/miR‐18b/miR‐106a cluster was associated with noncardia GC (minimum p‐value = 5.40 × 10−3; OR = 1.41, 95% CI = 1.12–1.78). Some functionally validated target genes of these miRNAs are implicated in cancer‐related processes such as methylation (DNMT3A, DNMT3B), cell cycle (E2F1, CDKN1A, CDKN1C), apoptosis (BCL2L11, MCL1), angiogenesis (VEGFA) and progression (PIK3R1, MYCN). Furthermore, we identified genetic interactions between variants tagging these miRNAs and variants in their validated target genes. Deregulation of the expression of these miRNAs in GC also supports our findings, altogether suggesting for the fist time that genetic variation in MIR29, MIR25, MIR93 and MIR106b may have a critical role in genetic susceptibility to GC and could contribute to the molecular mechanisms of gastric carcinogenesis.
What's New?
Even though deregulation of miRNA expression has been associated with human cancers, the contribution of miRNAs to cancer genetic susceptibility is unclear. Here the authors designed a panel of 133 SNPs tagging 104 candidate miRNA genes and analysed their association with gastric cancer (GC). They describe an unreported significant genetic association of GC with miRNA clusters in chromosomes 7 and X including miR‐29, miR‐25, miR‐93, and miR‐106. These miRNAs have been previously involved in the pathophysiology of GC and have functionally validated target genes implicated in cancer‐related processes. The data suggest these miRNAs as novel genetic susceptibility factors for GC.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Although recent studies suggest that high intakes of meat and heme iron are risk factors for several types of cancer, studies in relation to esophageal adenocarcinoma (EAC) are scarce. Previous ...results in the European Prospective Investigation into Cancer and Nutrition (EPIC) based on a relatively small number of cases suggested a positive association between processed meat and EAC. In this study, we investigate the association between intake of different types of meats and heme iron intake and EAC risk in a larger number of cases from EPIC. The study included 481,419 individuals and 137 incident cases of EAC that occurred during an average of 11 years of follow‐up. Dietary intake of meat (unprocessed/processed red and white meat) was assessed by validated center‐specific questionnaires. Heme iron was calculated as a type‐specific percentage of the total iron content in meat. After adjusting for relevant confounders, we observed a statistically significant positive association of EAC risk with heme iron and processed meat intake, with HR: 1.67, 95% CI: 1.05–2.68 and HR: 2.27, 95% CI:1.33–3.89, respectively, for comparison of the highest vs. lowest tertile of intake. Our results suggest a potential association between higher intakes of processed meat and heme iron and risk of EAC.
What's new?
Previous results have shown that eating red meat can increase one's risk of developing certain cancers, including esophageal adenocarcinoma (EAC). That work included few cases of EAC, however. This study expands on those findings by investigating the effect of eating different kinds of meats and includes a larger number of esophageal cancer cases. Using a questionnaire, they assessed the amount of processed and unprocessed red or white meat consumed by individuals, including 137 EAC patients. They also estimated the amount of heme iron consumed based on the amount and types of meat eaten by the study subject. The analysis shows that consumption of processed meat and heme iron appear to be associated with higher risk of esophageal adenocarcinoma.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Disturbances in one carbon metabolism may contribute to carcinogenesis by affecting methylation and synthesis of DNA. Choline and its oxidation product betaine are involved in this metabolism and can ...serve as alternative methyl group donors when folate status is low.
We conducted a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), to investigate plasma concentrations of the methyl donors methionine, choline, betaine (trimethylglycine), and dimethylglycine (DMG) in relation to colorectal cancer (CRC) risk. Our study included 1367 incident CRC cases (965 colon and 402 rectum) and 2323 controls matched by gender, age group, and study center. Multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for CRC risk were estimated by conditional logistic regression, comparing the fifth to the first quintile of plasma concentrations.
Overall, methionine (OR: 0.79, 95% CI: 0.63–0.99, P-trend = 0.05), choline (OR: 0.77, 95% CI: 0.60–0.99, P-trend = 0.07), and betaine (OR: 0.85, 95% CI: 0.66–1.09, P-trend = 0.06) concentrations were inversely associated with CRC risk of borderline significance. In participants with folate concentration below the median of 11.3nmol/l, high betaine concentration was associated with reduced CRC risk (OR: 0.71, 95% CI: 0.50–1.00, P-trend = 0.02), which was not observed for those having a higher folate status. Among women, but not men, high choline concentration was associated with decreased CRC risk (OR: 0.62, 95% CI: 0.43–0.88, P-trend = 0.01). Plasma DMG was not associated with CRC risk.
Individuals with high plasma concentrations of methionine, choline, and betaine may be at reduced risk of CRC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Vegetable and/or fruit intakes in association with hepatocellular carcinoma (HCC) risk have been investigated in case-control studies conducted in specific European countries and cohort studies ...conducted in Asia, with inconclusive results. No multi-centre European cohort has investigated the indicated associations.
In 486,799 men/women from the European Prospective Investigation into Cancer and nutrition, we identified 201 HCC cases after 11 years median follow-up. We calculated adjusted hazard ratios (HRs) for HCC incidence for sex-specific quintiles and per 100 g d(-1) increments of vegetable/fruit intakes.
Higher vegetable intake was associated with a statistically significant, monotonic reduction of HCC risk: HR (100 g d(-1) increment): 0.83; 95% CI: 0.71-0.98. This association was consistent in sensitivity analyses with no apparent heterogeneity across strata of HCC risk factors. Fruit intake was not associated with HCC incidence: HR (100 g d(-1) increment): 1.01; 95% CI: 0.92-1.11.
Vegetable, but not fruit, intake is associated with lower HCC risk with no evidence for heterogeneity of this association in strata of important HCC risk factors. Mechanistic studies should clarify pathways underlying this association. Given that HCC prognosis is poor and that vegetables are practically universally accessible, our results may be important, especially for those at high risk for the disease.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
While higher intake of fish and lower consumption of red/processed meats have been suggested to play a protective role in the etiology of several cancers, prospective evidence for hepatocellular ...carcinoma (HCC) is limited, particularly in Western European populations.
The associations of fish and meats with HCC risk were analyzed in the EPIC cohort. Between 1992 and 2010, 191 incident HCC were identified among 477 206 participants. Baseline diet was assessed using validated dietary questionnaires. A single 24-h diet recall from a cohort subsample was used for calibration. Multivariable proportional hazard regression was utilized to estimate hazard ratios (HR) and 95% confidence intervals (CI). In a nested case–control subset (HCC = 122), HBV/HCV status and liver function biomarkers were measured.
HCC risk was inversely associated with intake of total fish (per 20 g/day increase, HR = 0.83, 95% CI 0.74–0.95 and HR = 0.80, 95% CI 0.69–0.97 before and after calibration, respectively). This inverse association was also suggested after adjusting for HBV/HCV status and liver function score (per 20-g/day increase, RR = 0.86, 95% CI 0.66–1.11 and RR = 0.74, 95% CI 0.50–1.09, respectively) in a nested case–control subset. Intakes of total meats or subgroups of red/processed meats, and poultry were not associated with HCC risk.
In this large European cohort, total fish intake is associated with lower HCC risk.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Objective
We introduce and review the concept of a study-a-thon as a catalyst for open science in medicine, utilizing harmonized real world, observation health data, tools, skills, and ...methods to conduct network studies, generating insights for those wishing to use study-a-thons for future research.
Materials and Methods
A series of historical study-a-thons since 2017 to present were reviewed for thematic insights as to the opportunity to accelerate the research method to conduct studies across therapeutic areas. Review of publications and experience of the authors generated insights to illustrate the conduct of study-a-thons, key learning, and direction for those wishing to conduct future such study-a-thons.
Results
A review of six study-a-thons have provided insights into their scientific impact, and 13 areas of insights for those wishing to conduct future study-a-thons. Defining aspects of the study-a-thon method for rapid, collaborative research through network studies reinforce the need to clear scientific rationale, tools, skills, and methods being collaboratively to conduct a focused study. Well-characterized preparatory, execution and postevent phases, coalescing skills, experience, data, clinical input (ensuring representative clinical context to the research query), and well-defined, logical steps in conducting research via the study-a-thon method are critical.
Conclusions
A study-a-thon is a focused multiday research event generating reliable evidence on a specific medical topic across different countries and health systems. In a study-a-thon, a multidisciplinary team collaborate to create an accelerated contribution to scientific evidence and clinical practice. It critically accelerates the research process, without inhibiting the quality of the research output and evidence generation, through a reproducible process.
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