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Marina di Ragusa, Italy

Bella F.,Analytical Epidemiology and Health Impact Unit | Minicozzi P.,Analytical Epidemiology and Health Impact Unit | Giacomin A.,Epidemiology Unit | Crocetti E.,Clinical and Descriptive Epidemiology Unit | And 8 more authors.
Journal of Cancer Research and Clinical Oncology

Purpose: Diabetes is associated with increased risk of developing colorectal cancer (CRC), but its effect on overall and cancer-specific mortality in CRC patients has been little investigated. The aim of this study was to assess the influence of diabetes on overall and cancer-specific mortality in Italian CRC patients. Methods: Cases of adult (≥15 years) CRC, diagnosed in 2003-2005, most followed-up to the end of 2008, were randomly selected from the Italian Cancer Registries database. Diabetic status, sex, age, tumor stage, subsite, treatment, morphology, and grade were obtained by consultation of patient clinical records. Poisson multivariable regression models, adjusted for potential confounding variables, were used to estimate hazard ratios (HRs) for all-cause and CRC-specific mortality, according to diabetic status. Results: A total of 1,039 CRC cases with known fasting glucose or diabetic status, archived in 7 cancer registries, was analyzed. Compared to non-diabetics, diabetics (specific diagnosis or glucose ≥126 mg/dl) were older and less likely to receive adjuvant therapy. Diabetics were at higher risk of all-cause death [HR 1.41; 95 % confidence interval (CI) 1.18-1.70] and CRC death (HR 1.36; 95 % CI 1.11-1.67), with no differences by sex or subsite. Conclusions: Diabetes was significantly associated with increased overall and CRC-specific mortality. Our findings indicate that diabetes is a negative prognostic factor for CRC and suggest that in patients with CRC, diabetes prevention and treatments that stabilize the condition and control its complications might reduce mortality. Further studies are required to ascertain the mechanisms linking diabetes to greater mortality in CRC patients. © 2013 Springer-Verlag Berlin Heidelberg. Source

Campanella G.,Imperial College London | Polidoro S.,Human Genetics Foundation HuGeF | Di Gaetano C.,Human Genetics Foundation HuGeF | Fiorito G.,Human Genetics Foundation HuGeF | And 13 more authors.
International Journal of Epidemiology

Background: Observational studies have suggested that the risks of non-communicable diseases in voluntary migrants become similar to those in the host population after one or more generations, supporting the hypothesis that these diseases have a predominantly environmental (rather than inherited) origin. However, no study has been conducted thus far to identify alterations at the molecular level that might mediate these changes in disease risk after migration. Methods: Using genome-wide DNA methylation profiles from more than 1000 Italian participants, we conducted an epigenome-wide association study (EWAS) to identify differences between south-to-north migrants and their origin (southern natives) and host (north-western natives) populations. Results: We identified several differentially methylated CpG loci, in particular when comparing south-to-north migrants with north-western natives. We hypothesise that these alterations may underlie an adaptive response to exposure differentials that exist between origin and host populations. Conclusions: Our study is the first large agnostic investigation of DNA methylation changes linked to migratory processes, and shows the potential of EWAS to investigate their biological effects. © The Author 2014. Source

Hebels D.G.A.J.,Maastricht University | Georgiadis P.,National Hellenic Research Foundation | Keun H.C.,Imperial College London | Athersuch T.J.,Imperial College London | And 15 more authors.
Environmental Health Perspectives

Background: The suitability for omic analysis of biosamples collected in previous decades and currently stored in biobanks is unknown. Objectives: We evaluated the influence of handling and storage conditions of blood-derived biosamples on transcriptomic, epigenomic (CpG methylation), plasma metabolomic [UPLC-ToFMS (ultra performance liquid chromatography-time-of-flight mass spectrometry)], and wide-target proteomic profiles. Methods: We collected fresh blood samples without RNA preservative in heparin, EDTA, or citrate and held them at room temperature for ≤ 24 hr before fractionating them into buffy coat, erythrocytes, and plasma and freezing the fractions at-80°C or in liquid nitrogen. We developed methodology for isolating RNA from the buffy coats and conducted omic analyses. Finally, we analyzed analogous samples from the EPIC-Italy and Northern Sweden Health and Disease Study biobanks. Results: Microarray-quality RNA could be isolated from buffy coats (including most biobank samples) that had been frozen within 8 hr of blood collection by thawing the samples in RNA preservative. Different anticoagulants influenced the metabolomic, proteomic, and to a lesser extent transcriptomic profiles. Transcriptomic profiles were most affected by the delay (as little as 2 hr) before blood fractionation, whereas storage temperature had minimal impact. Effects on metabolomic and proteomic profiles were noted in samples processed ≥ 8 hr after collection, but no effects were due to storage temperature. None of the variables examined significantly influenced the epigenomic profiles. No systematic influence of tim-in-storage was observed in samples stored over a period of 13-17 years. Conclusions: Most samples currently stored in biobanks are amenable to meaningful omics analysis, provided that they satisfy collection and storage criteria defined in this study. Source

Benetou V.,National and Kapodistrian University of Athens | Orfanos P.,National and Kapodistrian University of Athens | Pettersson-Kymmer U.,Umea University | Bergstrom U.,Umea University | And 18 more authors.
Osteoporosis International

Prevention of hip fractures is of critical public health importance. In a cohort of adults from eight European countries, evidence was found that increased adherence to Mediterranean diet, measured by a 10-unit dietary score, is associated with reduced hip fracture incidence, particularly among men. Introduction: Evidence on the role of dietary patterns on hip fracture incidence is scarce. We explored the association of adherence to Mediterranean diet (MD) with hip fracture incidence in a cohort from eight European countries. Methods: A total of 188,795 eligible participants (48,814 men and 139,981 women) in the European Prospective Investigation into Cancer and nutrition study with mean age 48.6 years (±10.8) were followed for a median of 9 years, and 802 incident hip fractures were recorded. Diet was assessed at baseline through validated dietary instruments. Adherence to MD was evaluated by a MD score (MDs), on a 10-point scale, in which monounsaturated were substituted with unsaturated lipids. Association with hip fracture incidence was assessed through Cox regression with adjustment for potential confounders. Results: Increased adherence to MD was associated with a 7 % decrease in hip fracture incidence [hazard ratio (HR) per 1-unit increase in the MDs 0.93; 95 % confidence interval (95 % CI) = 0.89-0.98]. This association was more evident among men and somewhat stronger among older individuals. Using increments close to one standard deviation of daily intake, in the overall sample, high vegetable (HR = 0.86; 95 % CI = 0.79-0.94) and high fruit (HR = 0.89; 95 % CI = 0.82-0.97) intake was associated with decreased hip fracture incidence, whereas high meat intake (HR = 1.18; 95 % CI = 1.06-1.31) with increased incidence. Excessive ethanol consumption (HR high versus moderate = 1.74; 95 % CI = 1.32-2.31) was also a risk factor. Conclusions: In a prospective study of adults, increased adherence to MD appears to protect against hip fracture occurrence, particularly among men. © 2012 International Osteoporosis Foundation and National Osteoporosis Foundation. Source

Sieri S.,Italian National Cancer Institute | Pala V.,Italian National Cancer Institute | Brighenti F.,University of Parma | Agnoli C.,Italian National Cancer Institute | And 12 more authors.
Nutrition, Metabolism and Cardiovascular Diseases

Background and aims: There are theoretical reasons for suspecting that a high glycemic index (GI) or glycemic load (GL) diet may increase breast cancer risk, perhaps via an effect on the insulin-like growth factor (IGF) axis. However observational studies have produced inconsistent findings and it is controversial whether breast cancer risk is influenced by the carbohydrate characteristics of the diet. We prospectively investigated the association between dietary GI and GL and breast cancer in the Italian section of the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods and results: Women were recruited from 1993 to 1998 at five centers: Varese and Turin (north Italy), Florence (central Italy), and Ragusa and Naples (south Italy). Participants completed validated food frequency questionnaires from which GI and GL were estimated. Multivariable Cox proportional hazard regression models quantified the association between breast cancer risk and total carbohydrate intake, GI, and GL. During 11 years of follow-up, 879 breast cancer (797 invasive and 82 in situ) cases were indentified. High dietary GL was associated with increased breast cancer risk (RR 1.45, 95% CI=1.06-1.99; highest vs. lowest quintile; p-trend 0.029), whereas dietary GI and total carbohydrate had no influence. The association was not modified by menopausal status or body mass index. Conclusion: Our data indicate that, in a Mediterranean population characterized by traditionally high and varied carbohydrate intake, a diet high in GL plays a role in the development of breast cancer. © 2012 Elsevier B.V. Source

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