Suchergebnisse

Background: Gene-diet interactions have been reported to contribute to the development of type 2 diabetes (T2D). However, to our knowledge, few examples have been consistently replicated to date. Objective: We aimed to identify existing evidence for genemacronutrient interactions and T2D and to examine the reported interactions in a large-scale study. Design: We systematically reviewed studies reporting genemacronutrient interactions and T2D. We searched the MEDLINE, Human Genome Epidemiology Network, and WHO International Clinical Trials Registry Platform electronic databases to identify studies published up to October 2015. Eligibility criteria included assessment of macronutrient quantity (e.g., total carbohydrate) or indicators of quality (e.g., dietary fiber) by use of self-report or objective biomarkers of intake. Interactions identified in the review were subsequently examined in the EPIC (European Prospective Investigation into Cancer)-InterAct case-cohort study (n = 21,148, with 9403 T2D cases; 8 European countries). Prentice-weighted Cox regression was used to estimate country-specific HRs, 95% CIs, and P-interaction values, which were then pooled by random-effects meta-analysis. A primary model was fitted by using the same covariates as reported in the published studies, and a second model adjusted for additional covariates and estimated the effects of isocaloric macronutrient substitution. Results: Thirteen observational studies met the eligibility criteria (n , 1700 cases). Eight unique interactions were reported to be significant between macronutrients [carbohydrate, fat, saturated fat, dietary fiber, and glycemic load derived from self-report of dietary intake and circulating n–3 (v-3) polyunsaturated fatty acids] and genetic variants in or near transcription factor 7–like 2 (TCF7L2), gastric inhibitory polypeptide receptor (GIPR), caveolin 2 (CAV2), and peptidase D (PEPD) (P-interaction , 0.05). We found no evidence of interaction when we tried to replicate previously reported interactions. In addition, no interactions were detected in models with additional covariates. Conclusions: Eight gene-macronutrient interactions were identified for the risk of T2D from the literature. These interactions were not replicated in the EPIC-InterAct study, which mirrored the analyses undertaken in the original reports. Our findings highlight the importance of independent replication of reported interactions. ; Funding for the InterAct project was provided by the EU FP6 programme (grant number LSHM_CT_2006_037197). In addition, InterAct investigators acknowledge funding from the following agencies: Medical Research Council Epidemiology Unit MC_UU_12015/1 and MC_UU_12015/5, and Medical Research Council Human Nutrition Research MC_UP_A090_1006 and Cambridge Lipidomics Biomarker Research Initiative G0800783. IS, JWJB and YTvdS: Verification of diabetes cases was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht (The Netherlands; HBBdM, AMWS and DLvdA: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); German Federal Ministry of Education and Research (BMBF) and the State of Brandenburg to the German Center for Diabetes Research (DZD); FLC: Cancer Research UK C8221/A19170 and C570/A16491 and Medical Research Council MR/M012190/1; PWF: Swedish Research Council, Novo Nordisk, Swedish Heart Lung Foundation, Swedish Diabetes Association; JH, KO and AT: Danish Cancer Society; RK: Deutsche Krebshilfe; SP: Associazione Italiana per la Ricerca sul Cancro; JRQ: Asturias Regional Government; MT: Health Research Fund (FIS) of the Spanish Ministry of Health; Navarre Regional Government; the CIBER en Epidemiología y Salud Pública (CIBERESP), Spain; Murcia Regional Government (Nº 6236); RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government; Red Temática de Investigación Cooperativa en Cáncer of the Instituto de Salud Carlos III (ISCIII RTICC RD12/0036/0018), cofounded by FEDER funds/European Regional Development Fund (ERDF); German Cancer Aid, German Ministry of Research (BMBF); Compagnia di San Paolo; Imperial College Biomedical Research Centre.

BACKGROUND: Leakage of bacterial products across the gut barrier may play a role in liver diseases which often precede the development of liver cancer. However, human studies, particularly from prospective settings, are lacking. METHODS: We used a case-control study design nested within a large prospective cohort to assess the association between circulating levels of anti-lipopolysaccharide (LPS) and anti-flagellin immunoglobulin A (IgA) and G (IgG) (reflecting long-term exposures to LPS and flagellin, respectively) and risk of hepatocellular carcinoma. A total of 139 men and women diagnosed with hepatocellular carcinoma between 1992 and 2010 were matched to 139 control subjects. Multivariable rate ratios (RRs), including adjustment for potential confounders, hepatitis B/C positivity, and degree of liver dysfunction, were calculated with conditional logistic regression. RESULTS: Antibody response to LPS and flagellin was associated with a statistically significant increase in the risk of hepatocellular carcinoma (highest vs. lowest quartile: RR = 11.76, 95% confidence interval = 1.70-81.40; P trend = 0.021). This finding did not vary substantially by time from enrollment to diagnosis, and did not change after adjustment for chronic infection with hepatitis B and C viruses. CONCLUSIONS: These novel findings, based on exposures up to several years prior to diagnosis, support a role for gut-derived bacterial products in hepatocellular carcinoma development. Further study into the role of gut barrier failure and exposure to bacterial products in liver diseases is warranted. ; This work was supported by the French National Cancer Institute (L'Institut National du Cancer; INCA) (grant number 2009-139; Principal Investigator: M. Jenab). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); the Sicilian Government, AIRE ONLUS Ragusa, AVIS Ragusa, Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands); Nordic Centre of Excellence programme on Food, Nutrition and Health. (Norway); Health Research Fund (FIS), PI13/00061 to Granada), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, Regional Government of Asturias (Asturias, Spain), and ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council, and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 to EPIC-Oxford) and Medical Research Council (1000143 to EPIC-Norfolk) (United Kingdom); and a Girdlers' New Zealand Health Research Council Fellowship (to Dr. K.E. Bradbury). The funding sources had no influence on the design of the study; the collection, analysis, and interpretation of data; the writing of the report; or the decision to submit the paper for publication.