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Breast cancer is the most common malignancy among women worldwide. Various studies indicate that prolonged exposure to elevated levels of estrogens is associated with development of breast cancer. Both estrogen receptor-dependent and independent mechanisms can contribute to the carcinogenic effects of estrogens. Among them, the oxidative metabolism of estrogens plays a key role in the initiation of estradiol-induced breast cancer by generation of reactive estrogen quinones as well as the associated formation of oxygen free radicals. These genotoxic metabolites can react with DNA to form unstable DNA adducts which generate mutations leading to the initiation of breast cancer. A variety of endogenous and exogenous factors can alter estrogen homeostasis and generate genotoxic metabolites. The use of specific phytochemicals and dietary supplements can inhibit the risk of breast cancer not only by the modulation of several estrogen-activating enzymes (CYP19, CYP1B1) but also through the induction of various cytoprotective enzymes (eg, SOD3, NQO1, glutathione S-transferases, OGG-1, catechol-O-methyltransferases, CYP1B1A, etc.) that reestablish the homeostatic balance of estrogen metabolism via nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent and independent mechanisms.

The aim of this study was to investigate the relation between bladder cancer risk and the use of selected drugs for cardiovascular disease (CVD) prevention, such as aspirin, statins, and calcium channel blockers (CCBs). We analyzed data from a multicentric case-control study carried out in Italy between 2003 and 2014, including 690 bladder cancer cases and 665 hospital controls. Odds ratios (ORs) of bladder cancer and corresponding 95% confidence intervals (CIs) were estimated using unconditional multiple logistic regression models. The ORs for bladder cancer were 1.21 (95% CI: 0.87-1.68) for regular use of aspirin, 0.72 (95% CI: 0.54-0.97) for use of any CCBs, and 1.32 (95% CI: 0.87-1.99) for use of any statins. A slight inverse association was found with duration of use of CCBs, whereas no consistent association was found with duration of use, age at first use, and frequency for aspirin and statin use, or with indication of use for aspirin (as an analgesic or, for CVD prevention). No significant association was found for various combinations of drugs or for all drugs combined (OR=1.23, 95% CI: 0.31-4.85). Our data indicate the lack of a relevant association between the use of selected drugs for CVD prevention and bladder cancer risk, although suggest a potential favorable role for CCBs.

Background:Previous studies suggested a link between obesity, insulin-resistance and breast cancer outcome. The aim of the present prospective observational study was to investigate the role of metabolic syndrome (MetS) and its components on early breast cancer (EBC) patients' outcome. Methods: MetS was defined by the presence of 3 to 5 of the following components: waist circumference (WC) > 88 cm, blood pressure ≥ 130/≥85 mmHg, serum levels of triglycerides (TG) ≥ 150 mg/dL, high-density lipoprotein (HDL) < 50 mg/dL and fasting glucose (FG) ≥ 110 mg/ dL (National Cholesterol Education Program Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults - NCEP-ATPIII criteria). Overall, 955 EBC patients were prospectively enrolled between January 2009 and December 2013 at University Hospital Federico II and National Cancer Institute G.Pascale, Naples, Italy. Clinical and tumor characteristics were collected for all the patients. A total of 494 patients (51.7%) had complete data on all the components of MetS at first diagnosis and thus were included in the current analysis. Study population was divided into 2 main groups: (1) patients with less than 3 components (No MetS); (2) patients with 3-5 components (MetS). Categorical variables were analyzed by the chi-square test and survival data by the log-rank test and Cox proportional hazards regression model. Results: Overall 366 (74.1%) and 128 (25.9%) women were categorized as No MetS and MetS, respectively. MetS patients were more likely to be older and postmenopausal compared to No MetS patients. In detail, 46% vs 38% were older than 55 yrs (p Conclusions: MetS is correlated with poor outcome in EBC patients. Among patients without full criteria for MetS diagnosis, the presence of 1 or 2 components of the syndrome may predict for worse survival. Testing for components of MetS in BC patients is recomended to predict outcome and to eventually suggest lifestyle changes, exercise and diet. Citation Format: Buono G, Crispo A, Giuliano M, Rea CG, Forestieri V, Lauria R, De Placido P, De Laurentiis M, Pacilio C, Grimaldi M, Nocerino F, Montella M, De Placido S, Arpino G. Metabolic syndrome and early-stage breast cancer outcome: Results from a prospective observational study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-15.

Background we have recently shown that Tel-eVax, a genetic vaccine targeting dog telomerase (dTERT) and based on Adenovirus (Ad)/DNA Electro-Gene-Transfer (DNA–EGT) technology can induce strong immune response and increase overall survival (OS) of dogs affected by multicentric Diffuse Large B cell Lymphoma (DLBCL) when combined to COP therapy in a double-arm study. Here, we have utilized a clinically validated device for veterinary electroporation called Vet-ePorator™, based on Cliniporator™ technology currently utilized and approved in Europe for electrochemotherapy applications and adapted to electrogenetransfer (EGT). Methods 17 dogs affected by DLBCL were vaccinated using two Ad vector injections (Prime phase) followed by DNA–EGT (Boost phase) by means of a Vet-ePorator™ device and treated in the same time with a 27-week Madison Wisconsin CHOP protocol. The immune response was measured by ELISA assays using pool of peptides. Results No significant adverse effects were observed. The OS of vaccine/CHOP animals was 64.5 weeks, in line with the previous study. Dogs developed antibodies against the immunizing antigen. Conclusions Tel-eVax in combination with CHOP is safe and immunogenic in lymphoma canine patients. These data confirm the therapeutic efficacy of dTERT vaccine and hold promise for the treatment of dogs affected by other cancer types. More importantly, our findings may translate to human clinical trials and represent new strategies for cancer treatment.

Evidence suggests a beneficial role of the Mediterranean Diet (MedDiet) on health-related quality of life (HRQoL) in healthy subjects. HRQoL is relevant in cancer therapy and disease outcomes, therefore we investigated the association between adherence to the MedDiet and HRQoL in breast cancer survivors participating in the multicentre trial DEDiCa. Diet and HRQoL were assessed at baseline in a subgroup of 309 women enrolled within 12 months of breast cancer diagnosis without metastasis (stages I-III, mean age 52±1 yrs, BMI 27±7 kg/m2). The 14-item PREDIMED questionnaire was used to analyse adherence to the MedDiet. HRQoL was assessed with three validated questionnaires measuring physical, mental, emotional and social factors: EQ-5D-3L, EORTC QLQ-C30 and EORTC QLQ-BR23. Analysis of variance (ANOVA) and multivariate analyses were performed to assess the possible role of the MedDiet on HRQoL. Patients with higher adherence to MedDiet (PREDIMED score >7) showed significantly higher scores for physical functioning (p = 0.02) and lower scores on the symptomatic pain scale (p = 0.04) assessed by the EORTC QLQ-C30 questionnaire compared to patients with a lower adherence to MedDiet (PREDIMED score ≤7). Higher scores from the EQ-5D-3L indicating higher well-being were observed mainly in participants with higher MedDiet adherence (p = 0.05). In adjusted multivariate analyses significant positive associations were found between MedDiet, physical functioning (p = 0.001) and EQ 5D-3L score (p = 0.003) while inverse associations were found with pain and insomnia symptoms (p = 0.005 and p = 0.029, respectively). These results suggest that higher adherence to the MedDiet in breast cancer survivors is associated with better aspects of quality of life, specifically higher physical functioning, better sleep, lower pain and generally higher well-being confirming findings in healthy subjects.

Arsenic and arsenic-derivative compounds, named as arsenicals, represent a worldwide problem for their effect on the human health and, in particular, for their capability to increase the risk of developing cancer such as kidney, bladder and prostate cancer. The main source of arsenical exposure is drinking water. Nowadays, it is well known that the chronic exposure to arsenicals leads to a series of epigenetic alterations that have a role in arsenic-induced effects on human health including cancer. Based on these observations, the aim of our study was to select by network analysis the genes/proteins/miRNAs implicated in kidney, bladder and prostate cancer development upon arsenical exposure. From this analysis we identified: (i) the nodes linking the three molecular networks specific for kidney, bladder and prostate cancer; (ii) the relative HUB nodes (RXRA, MAP3K7, NR3C1, PABPC1, NDRG1, RELA and CTNNB1) that link the three cancer networks; (iii) the miRNAs able to target these HUB nodes. In conclusion, we highlighted a panel of potential molecules related to the molecular mechanisms of arsenical-induced cancerogenesis and suggest their utility as biomarkers or therapeutic targets.

Background/objectives: To assess the association between processed meat and the risk of selected digestive tract and laryngeal cancers. Subjects/methods: We conducted a series of case-control studies between 1985 and 2007 in Italy. The studies included a total of 1475 cases of cancer of the oral cavity and pharynx, 1077 of the larynx, 716 of the esophagus, 999 of the stomach, 684 of the liver, 159 of the biliary tract, 688 of the pancreas, and a total of 9720 controls. Odds ratios (ORs), and the corresponding 95% confidence intervals (CIs), were estimated by unconditional logistic regression models, including terms for socio-demographic factors, tobacco smoking, and alcohol intake. Results: Compared to the lowest tertile of processed meat consumption, the ORs for subjects in the highest one were 1.18 (95% CI 0.98–1.43) for oral cavity and pharyngeal, 1.51 (95% CI 1.18–1.91) for esophageal, 1.19 (95% CI 0.96–1.47) for laryngeal, 0.98 (95% CI 0.81–1.18) for stomach, 0.85 (95% CI 0.51–1.40) for biliary tract, 1.20 (95% CI 0.94–1.54) for liver, and 1.46 (95% CI 1.15–1.85) for pancreatic cancers. Conclusions: Our findings support the hypothesis that high processed meat consumption increases esophageal and pancreatic cancers risk. Residual confounding by socio-demographic factors, tobacco smoking, and alcohol intake may, partly or largely, account for these associations. We found no overall association with other digestive tract and laryngeal cancers.

The aim of this study is to evaluate the association between metabolic disorders and the risk of nasopharyngeal carcinoma, considering different histological subtypes. Between 1992 and 2008, we carried out a multicentre case-control study in Italy. One-hundred and ninety-seven White patients with histologically confirmed nasopharyngeal carcinoma were enrolled as cases. The control group included 592 cancer-free patients, frequency matched by study centre, area of residence, sex, age and period of interview. Odds ratios (OR) and corresponding 95% confidence intervals (CI), for nasopharyngeal carcinoma according to obesity and self-reported history of other metabolic disorders, were calculated through logistic regression models adjusted for matching variables and tobacco smoking and drinking habits. Obesity (OR=1.44; 95% CI: 0.88-2.36), diabetes mellitus (OR=0.91; 95% CI: 0.42-1.98), hypertension (OR=0.79; 95% CI: 0.48-1.32), hypercholesterolaemia (OR=1.41; 95% CI: 0.84-2.35) and metabolic syndrome (i.e. at least three among the four previously cited metabolic disorders; OR=1.11; 95% CI: 0.86-1.43) were not significantly associated with the overall risk of nasopharyngeal carcinoma. However, the associations observed for diabetes mellitus, hypercholesterolaemia and metabolic syndrome were stronger among differentiated nasopharyngeal carcinomas than among undifferentiated ones. In particular, 21.7% of differentiated nasopharyngeal carcinoma cases and 7.8% of controls reported a history of metabolic syndrome (OR=3.37; 95% CI: 1.05-10.81). The results of the study indicated no overall association between metabolic disorders and nasopharyngeal carcinoma. Nonetheless, although the small sample size calls for caution in interpretation, metabolic disorders could increase the risk of differentiated nasopharyngeal carcinoma. This finding further supports a different aetiology of the two histological subtypes.

BACKGROUND: The World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) released in 2007 eight recommendations for cancer prevention on body fatness, diet and physical activity. Our aim is to evaluate the relation between adherence to these recommendations and colorectal cancer (CRC) risk. METHODS: We pooled data from two Italian case-control studies including overall 2419 patients with CRC and 4723 controls. Adherence to the WCRF/AICR guidelines was summarised through a score incorporating seven of the WCRF/AICR recommendations, with higher scores indicating higher adherence to the guidelines. Odds ratios (ORs) of colorectal cancer were estimated using multiple logistic regression models. RESULTS: Higher adherence to the WCRF/AICR recommendations was associated with a significantly reduced CRC risk (OR 0.67, 95% confidence interval, CI, 0.56-0.80 for a score ≥5 versus

Carbohydrate foods with high glycaemic index (GI) and load (GL) may negatively influence cancer risk. We studied the association of dietary carbohydrates, GI, GL, intake of bread and pasta with risk of bladder cancer using data from an Italian case–control study. The study included 578 men and women with histologically confirmed bladder cancer and 608 controls admitted to the same hospitals as cases for acute, non-neoplastic conditions. OR were estimated by logistic regression models after allowance for relevant confounding factors. OR of bladder cancer for the highest v. the lowest quantile of intake were 1·52 (95 % CI 0·85, 2·69) for available carbohydrates, 1·18 (95 % CI 0·83, 1·67) for GI, 1·96 (95 % CI 1·16, 3·31, PtrendPtrend=0·03) for pasta and 1·92 (95 % CI 1·28, 2·86, Ptrend

The relation between diet-related inflammation and renal cell carcinoma (RCC) has not been investigated.In this study, we explored the association between the dietary inflammatory index (DII) and RCC in an Italian case-control study conducted between 1992 and 2004. Cases were 767 patients with incident, histologically confirmed RCC. Controls were 1534 subjects admitted to the same hospitals as cases for various acute, nonneoplastic conditions. The DII was computed based on dietary intake assessed using a reproducible and valid 78-item food frequency questionnaire. Odds ratios (ORs) were estimated through logistic regression models conditioned on age, sex, and center, and adjusted for recognized confounding factors, including total energy intake.Subjects in the highest quartile of DII scores (i.e., with the most proinflammatory diets) had a higher risk of RCC compared to subjects in the lowest quartile [OR 1.41, 95% confidence interval (CI) 1.02, 1.97; p-trend = 0.04)]. Apparently stronger associations were observed among females (OR 1.68, 95% CI 0.93, 3.03), subjects aged60 yr (OR 1.77, 95% CI 1.05, 2.98), body mass index ≥25 kg/mA proinflammatory diet is associated with increased RCC risk.

While dietary factors have been shown to play an important etiologic role in non-Hodgkin lymphoma (NHL), little is known about the association between inflammatory properties of diet and NHL risk. We explored the association between the dietary inflammatory index (DII) and NHL risk in a multicenter Italian case–control study conducted between 1999 and 2014. Cases were 536 subjects with incident, histologically confirmed NHL from three areas in Italy. Controls were 984 subjects admitted to the same network of hospitals as the cases for acute, nonmalignant conditions, unrelated to diet. DII scores were computed based on 30 nutrients and food items assessed using a reproducible and validated 78-item food-frequency questionnaire. Odds ratios (ORs) were estimated through logistic regression models adjusting for age, total energy intake, and other recognized confounding factors. Subjects in the highest quartile of DII scores (i.e., with the most pro-inflammatory diets) had a higher risk of NHL compared with subjects in the lowest quartile (i.e., with the most anti-inflammatory diets) (ORQuartile4vs1 1.61, 95% confidence interval CI 1.07–2.43; p-trend = 0.01). Stratified analyses produced stronger associations between DII and NHL among males (ORQuartile4vs1 2.14; 95% CI 1.25–3.67) with significant heterogeneity (p value = 0.02); when analyzed by histologic subtype, a significant association was observed with diffuse large B-cell lymphoma (ORQuartile4vs1 1.84; 95% CI 1.09–3.10). A pro-inflammatory diet, as indicated by higher DII scores, is associated with elevated odds of NHL, especially among males.

// Daniela Vanacore 1, 2, * , Mariarosaria Boccellino 2, * , Sabrina Rossetti 1, 3 , Carla Cavaliere 1, 4 , Carmine D’Aniello 1, 5 , Rossella Di Franco 1, 6 , Francesco Jacopo Romano 1 , Micaela Montanari 1, 7 , Elvira La Mantia 1, 8 , Raffaele Piscitelli 1, 9 , Flavia Nocerino 1, 10 , Francesca Cappuccio 1, 11 , Giovanni Grimaldi 1, 12 , Alessandro Izzo 1, 12 , Luigi Castaldo 1, 12 , Maria Filomena Pepe 1, 8 , Maria Gabriella Malzone 1, 8 , Gelsomina Iovane 3 , Gianluca Ametrano 1, 6 , Paola Stiuso 2 , Lucio Quagliuolo 2 , Daniela Barberio 1, 11 , Sisto Perdona 12 , Paolo Muto 6 , Maurizio Montella 10 , Piera Maiolino 9 , Bianca Maria Veneziani 7 , Gerardo Botti 8, 13 , Michele Caraglia 2 and Gaetano Facchini 1, 3 1 Progetto ONCONET2.0, Linea progettuale 14 per l’implementazione della Prevenzione e Diagnosi Precoce del Tumore alla Prostata e Testicolo, Regione Campania, Italy 2 Department of Biochemistry, Biophysics and General Pathology, University of Campania “L. Vanvitelli” Naples, Naples, Italy 3 Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori ‘Fondazione G. Pascale’, IRCCS, Naples, Italy 4 Department of Onco-Ematology Medical Oncology, S.G. Moscati Hospital of Taranto, Taranto, Italy 5 Division of Medical Oncology, A.O.R.N. dei COLLI “Ospedali Monaldi-Cotugno-CTO”, Napoli, Italy 6 Radiation Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale’, IRCCS, Napoli, Italy 7 Department of Molecular Medicine and Medical Biotechnologies, University of Naples “Federico II”, Naples, Italy 8 Pathology Unit, Istituto Nazionale Tumori “Fondazione G. Pascale”, IRCCS, Naples, Italy 9 Pharmacy Unit, Istituto Nazionale Tumori, Istituto Nazionale Tumori-Fondazione G. Pascale, Naples, Italy 10 Epidemiology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale’, IRCCS, Napoli, Italy 11 Psicology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale’, IRCCS, Napoli, Italy 12 Division of Urology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori ‘Fondazione G. Pascale’, IRCCS, Naples, Italy 13 Scientific Directorate, Istituto Nazionale Tumori ‘Fondazione G. Pascale’, IRCCS, Naples, Italy * These authors have contributed equally to this work Correspondence to: Michele Caraglia, email: michele.caraglia@unina2.it , michele.caraglia@alice.it Keywords: microRNAs, prostate cancer, biomarkers, oncogenic miRNAs, tumor suppressor miRNAs Received: February 06, 2017 Accepted: March 25, 2017 Published: April 07, 2017 ABSTRACT Prostate cancer is the second highest cause of cancer mortality after lung tumours. In USA it affects about 2.8 million men and the incidence increases with age in many countries. Therefore, early diagnosis is a very important step for patient clinical evaluation and for a selective and efficient therapy. The study of miRNAs’ functions and molecular mechanisms has brought new knowledge in biological processes of cancer. In prostate cancer there is a deregulation of several miRNAs that may function as tumour suppressors or oncogenes. The aim of this review is to analyze the progress made to our understanding of the role of miRNA dysregulation in prostate cancer tumourigenesis.

// Vincenzo Quagliariello 1,2,3,16 , Sabrina Rossetti 1,2 , Carla Cavaliere 1,4 , Rossella Di Palo 1,5 , Elvira Lamantia 1,6 , Luigi Castaldo 1,7 , Flavia Nocerino 8 , Gianluca Ametrano 1,5 , Francesca Cappuccio 1,9 , Gabriella Malzone 1,6 , Micaela Montanari 1,10 , Daniela Vanacore 1 , Francesco Jacopo Romano 1 , Raffaele Piscitelli 1,11 , Gelsomina Iovane 2 , Maria Filomena Pepe 1,6 , Massimiliano Berretta 12,16 , Carmine D’Aniello 1,13 , Sisto Perdona 7 , Paolo Muto 5 , Gerardo Botti 6 , Gennaro Ciliberto 14,17 , Bianca Maria Veneziani 10 , Francesco De Falco 9 , Piera Maiolino 11 , Michele Caraglia 15 , Maurizio Montella 8 , Rosario Vincenzo Iaffaioli 3,16 and Gaetano Facchini 1,2,16 1 Progetto ONCONET2.0 - Linea progettuale 14 per l’implementazione della prevenzione e diagnosi precoce del tumore alla prostata e testicolo, Regione Campania, Italy 2 Division of Medical Oncology, Department of Uro-Gynaecological Oncology , Istituto Nazionale Tumori ‘Fondazione G. Pascale’ - IRCCS, Naples, Italy 3 Medical Oncology, Abdominal Department, National Cancer Institute G. Pascale Foundation, Napoli, Italy 4 Department of Onco-Ematology Medical Oncology, S.G. Moscati Hospital of Taranto, Taranto, Italy 5 Radiation Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale’ - IRCCS, Napoli, Italy 6 Pathology Unit, Istituto Nazionale Tumori “Fondazione G. Pascale”-IRCCS, Naples, Italy 7 Division of Urology, Department of Uro-Gynaecological Oncology , Istituto Nazionale Tumori ‘Fondazione G. Pascale’ - IRCCS, Naples, Italy 8 Epidemiology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale’ - IRCCS, Napoli, Italy 9 Psicology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale’ - IRCCS, Napoli, Italy 10 Department of Molecular Medicine and Medical Biotechnologies, University of Naples “Federico II”, Naples, Italy 11 Pharmacy Unit, Istituto Nazionale Tumori, Istituto Nazionale Tumori-Fondazione G. Pascale, Naples, Italy 12 Department of Medical Oncology, CRO Aviano, National Cancer Institute, Aviano, Italy 13 Division of Medical Oncology, A.O.R.N. dei COLLI “Ospedali Monaldi-Cotugno-CTO”, Napoli, Italy 14 Scientific Directorate, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale’ - IRCCS, Napoli, Italy 15 Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy 16 Association for Multidisciplinary Studies in Oncology and Mediterranean Diet, Piazza Nicola Amore, Naples, Italy 17 Scientific Directorate, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Regina Elena’ - IRCCS, Roma, Italy Correspondence to: Vincenzo Quagliariello, email: // Keywords : metabolic syndrome, endocrine disruptors, prostate, cancer, nutrition Received : October 28, 2016 Accepted : February 06, 2017 Published : March 30, 2017 Abstract This review summarizes the main pathophysiological basis of the relationship between metabolic syndrome, endocrine disruptor exposure and prostate cancer that is the most common cancer among men in industrialized countries. Metabolic syndrome is a cluster of metabolic and hormonal factors having a central role in the initiation and recurrence of many western chronic diseases including hormonal-related cancers and it is considered as the world’s leading health problem in the coming years. Many biological factors correlate metabolic syndrome to prostate cancer and this review is aimed to focus, principally, on growth factors, cytokines, adipokines, central obesity, endocrine abnormalities and exposure to specific endocrine disruptors, a cluster of chemicals, to which we are daily exposed, with a hormone-like structure influencing oncogenes, tumor suppressors and proteins with a key role in metabolism, cell survival and chemo-resistance of prostate cancer cells. Finally, this review will analyze, from a molecular point of view, how specific foods could reduce the relative risk of incidence and recurrence of prostate cancer or inhibit the biological effects of endocrine disruptors on prostate cancer cells. On the basis of these considerations, prostate cancer remains a great health problem in terms of incidence and prevalence and interventional studies based on the treatment of metabolic syndrome in cancer patients, minimizing exposure to endocrine disruptors, could be a key point in the overall management of this disease.

Previous studies on the relationship between fluid intake and risk of bladder cancer have generally focused on beverages, and results have been inconsistent. We investigated the relationship between water intake and bladder cancer risk, considering water from both beverages and foods. Between 2003 and 2014 we conducted a multicenter hospital-based case-control study in Italy on 690 cases and 665 frequency-matched controls. Water intake for beverages and foods was computed using the Italian food composition database. Odds ratios (ORs) and the corresponding 95% confidence intervals (95%CIs) for water intake were estimated by unconditional multiple logistic regression models, adjusting for major risk factors for bladder cancer. In the control group, the 64.7% of water intake derived from beverages and 35.4% from foods. Comparing the highest with the lowest quartile of intake, water from beverages (OR=1.14; 95%CI: 0.82-1.59) and water from foods (OR=0.88; 95%CI: 0.61-1.28) were not significantly associated with bladder cancer risk. Some specific water sources showed significant associations with bladder cancer risk (e.g. water from vegetables, OR=0.58; 95%CI: 0.40-0.86). However, these associations may be due to the effect of other components contained in beverages and foods rather than to the water content itself. Considering the intakes of water from both beverages and foods, total water intake was not associated with bladder cancer risk.

// Francesco Jacopo Romano 1 , Sabrina Rossetti 1,2 , Vincenza Conteduca 3 , Giuseppe Schepisi 3 , Carla Cavaliere 1,4 , Rossella Di Franco 1,5 , Elvira La Mantia 1,6 , Luigi Castaldo 1,7 , Flavia Nocerino 8 , Gianluca Ametrano 1,5 , Francesca Cappuccio 1,9 , Gabriella Malzone 1,6 , Micaela Montanari 1,10 , Daniela Vanacore 1 , Vincenzo Quagliariello 1 , Raffaele Piscitelli 1,11 , Maria Filomena Pepe 1,6 , Massimiliano Berretta 12 , Carmine D’Aniello 1,13 , Sisto Perdona 7 , Paolo Muto 5 , Gerardo Botti 6 , Gennaro Ciliberto 14 , Bianca Maria Veneziani 10 , Francesco De Falco 9 , Piera Maiolino 11 , Michele Caraglia 15 , Maurizio Montella 8 , Ugo De Giorgi 3 and Gaetano Facchini 1,2 1 Progetto ONCONET2.0, Linea Progettuale 14 per L’implementazione della Prevenzione e Diagnosi Precoce del Tumore alla Prostata e Testicolo, Regione Campania, Italy 2 Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori ‘Fondazione G. Pascale’, IRCCS, Naples, Italy 3 Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy 4 Department of Onco-Ematology Medical Oncology, S.G. Moscati Hospital of Taranto, Taranto, Italy 5 Radiation Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale’, IRCCS, Napoli, Italy 6 Pathology Unit, Istituto Nazionale Tumori “Fondazione G. Pascale”-IRCCS, Naples, Italy 7 Department of Uro-Gynaecological Oncology, Division of Urology, Istituto Nazionale Tumori ‘Fondazione G. Pascale’, IRCCS, Naples, Italy 8 Epidemiology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale’, IRCCS, Napoli, Italy 9 Psicology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale’, IRCCS, Napoli, Italy 10 Department of Molecular Medicine and Medical Biotechnologies, University of Naples “Federico II”, Naples, Italy 11 Pharmacy Unit, Istituto Nazionale Tumori, Istituto Nazionale Tumori-Fondazione G. Pascale Naples, Italy 12 Department of Medical Oncology, CRO Aviano, National Cancer Institute, Aviano, Italy 13 Division of Medical Oncology, A.O.R.N. dei COLLI “Ospedali Monaldi-Cotugno-CTO”, Napoli, Italy 14 Scientific Directorate, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale’, IRCCS, Napoli, Italy 15 Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy Correspondence to: Francesco Jacopo Romano, email: // Keywords : testis; germ cell cancer; DDR; ATM; p53 Received : September 12, 2016 Accepted : October 19, 2016 Published : November 03, 2016 Abstract Notwithstanding the peculiar sensitivity to cisplatin-based treatment, resulting in a very high percentage of cures even in advanced stages of the disease, still we do not know the biological mechanisms that make Testicular Germ Cell Tumor (TGCT) “unique” in the oncology scene. p53 and MDM2 seem to play a pivotal role, according to several in vitro observations, but no correlation has been found between their mutational or expression status in tissue samples and patients clinical outcome. Furthermore, other players seem to be on stage: DNA Damage Repair Machinery (DDR) , especially Homologous Recombination (HR) proteins, above all Ataxia Telangiectasia Mutated (ATM), cooperates with p53 in response to DNA damage, activating apoptotic cascade and contributing to cell “fate”. Homologous Recombination deficiency has been assumed to be a Germ Cell Tumor characteristic underlying platinum-sensitivity , whereby Poly(ADP-ribose) polymerase (PARP), an enzyme involved in HR DNA repair, is an intriguing target: PARP inhibitors have already entered in clinical practice of other malignancies and trials are recruiting TGCT patients in order to validate their role in this disease. This paper aims to summarize evidence, trying to outline an overview of DDR implications not only in TGCT curability, but also in resistance to chemotherapy.

Background Since food metabolites are eliminated by the urinary tract, several studies have investigated the association between diet and bladder cancer risk. Recently, the World Cancer Research Fund International/American Institute for Cancer Research (WCRF/AICR) suggested a potential beneficial effect of some foods (mainly vegetables, fruit, and milk) in the development of bladder cancer. We investigated the association between food groups and bladder cancer risk, seeking insights into food diversity as well as meat cooking methods. Methods Data were derived from an Italian multicentre case–control study, conducted between 2003 and 2014, including 690 bladder cancer cases and 665 frequency-matched controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (95%CIs) for various dietary aspects were estimated by unconditional logistic regression models adjusted for energy intake and the major known risk factors for bladder cancer. Results Comparing the highest versus the lowest quartiles, consumption of vegetables (OR = 0.62; 95%CI: 0.44-0.88) and milk/yogurt (OR = 0.62; 95%CI: 0.44–0.87) reduced the risk of bladder cancer. Conversely, consumption of meat increased bladder cancer risk with an OR of 1.57 (95%CI: 1.07–2.31), particularly when the meat was stewed (OR = 1.47; 95%CI: 1.03–2.09) or roasted (OR = 1.41; 95%CI: 1.00–1.99). There was a suggestion that a diversified diet reduced the risk of bladder cancer, but this was not significant. Conclusions Our study consolidates the role of diet in bladder cancer aetiology, showing a reduced risk for vegetable and milk/yogurt consumption and an increased risk for meat consumption, especially when the meat is stewed or roasted.

Objectives The aim of this study was to evaluate whether the association between the inflammatory potential of one's diet and cancer risk varies across age groups in a population characterized by widespread use of the Mediterranean diet. Methods We analyzed data from a network of case-control studies conducted in Italy between 1991 and 2014. The studies included cancers of the oral cavity (n = 509), pharynx (n = 436), nasopharynx (n = 198), larynx (n = 459), esophagus (n = 304), stomach (n = 230), colon (n = 1225), rectum (n = 728), liver (n = 184), pancreas (n = 326), breast (n = 2569), endometrium (n = 454), ovary (n = 1031), prostate (n = 1294), kidney (n = 767), and bladder (n = 690). Controls were 13 563 patients hospitalized for acute, non-neoplastic conditions. Dietary inflammatory index (DII) scores were computed based on 31 food parameters assessed using a reproducible and validated food frequency questionnaire. Odds ratios were estimated through logistic regression models adjusting for recognized confounding factors. Results The DII increased with age, with lower scores among men than women, in individuals located in northern rather than in central or southern Italy, and in controls more than in cancer cases. After adjustment for cancer-specific potential confounders, an increasing DII score was directly associated with cancer risk for all considered cancer sites, except for liver and endometrium. Although the DII level varied across age groups, no heterogeneity in cancer risk emerged for any of the considered cancer sites. Conclusions In the Italian population, DII scores were higher in elderly than in middle-aged individuals. Although not directly affecting cancer risk, this finding may have important implications for the older population because elevated DII scores, indicating a proinflammatory diet, also have been associated with frailty.

Hyperglycemia and hyperinsulinemia may play a role in breast carcinogenesis and prediabetes and diabetes have been associated with increased breast cancer (BC) risk. However, whether BC molecular subtypes may modify these associations is less clear. We therefore investigated these associations in all cases and by BC molecular subtypes among women living in Southern Italy. Cases were 557 patients with non-metastatic incident BC and controls were 592 outpatients enrolled during the same period as cases and in the same hospital for skin-related non-malignant conditions. Adjusted multivariate logistic regression models were built to assess the risks of developing BC in the presence of prediabetes or diabetes. The analyses were repeated by strata of BC molecular subtypes: Luminal A, Luminal B, HER2+, and Triple Negative (TN). Prediabetes and diabetes were significantly associated with higher BC incidence after controlling for known risk factors (OR = 1.94, 95% CI 1.32-2.87 and OR = 2.46, 95% CI 1.38-4.37, respectively). Similar results were seen in Luminal A and B while in the TN subtype only prediabetes was associated with BC (OR = 2.43, 95% CI 1.11-5.32). Among HER2+ patients, only diabetes was significantly associated with BC risk (OR = 3.04, 95% CI 1.24-7.47). Furthermore, when postmenopausal HER2+ was split into hormone receptor positive versus negative, the association with diabetes remained significant only in the former (OR = 5.13, 95% CI 1.53-17.22). These results suggest that prediabetes and diabetes are strongly associated with BC incidence and that these metabolic conditions may be more relevant in the presence of breast cancer molecular subtypes with positive hormone receptors. J. Cell. Physiol. 232: 1144-1150, 2017. © 2016 Wiley Periodicals, Inc.

Bladder cancer is one of the leading cancer of the urinary tract. It is often diagnosed at advanced stage of the disease. To date, no specific and effective early detection biomarkers are available. Cancer development and progression are associated with the involvement of both epithelial-mesenchymal transition (EMT) and tumor microenvironment of which NGAL/MMP-9 complex represents the main player in bladder cancer. It is known that change in microRNAs (miRNAs) expression may result in gene modulation. Therefore, the identification of specific miRNAs associated with EMT pathway and NGAL/MMP-9 complex may be useful to detect the development of bladder cancer at early stages. On this ground, the expression levels of miRNAs in public available datasets of bladder cancer containing data of non-coding RNA profiling was evaluated. This analysis revealed a group of 16 miRNAs differentially expressed between bladder cancer patients and related healthy controls. By miRNA prediction tool (mirDIP), the relationship between the identified miRNAs and the EMT genes was established. Using the DIANA-mirPath (v.2) software, miRNAs, able to modulate the expression of NGAL and MMP-9 genes, were recognized. The results of this study provide evidence that the downregulated hsa-miR-145-5p and hsa-miR-214-3p may modulate the expression of both EMT and NGAL/MMP-9 pathways. Therefore, further validation analyses may confirm the usefulness of these selected miRNAs for predicting the development of bladder cancer at the early stage of the disease.

While inflammation has been shown to play an important etiologic role in ovarian carcinogenesis, little is known about the association between inflammatory properties of diet and ovarian cancer risk.We explored the association between the dietary inflammatory index (DII) and ovarian cancer risk in a multicentric Italian case-control study conducted between 1992 and 1999. Cases were 1,031 women with incident, histologically confirmed ovarian cancer from four areas in Italy. Controls were 2,411 women admitted to the same network of hospitals as the cases for acute, non-malignant and non-gynecological conditions, unrelated to hormonal or digestive-tract diseases or committed to long-term modifications of diet. DII scores were computed based on 31 nutrients and food items assessed using a reproducible and validated 78-item food frequency questionnaire. Odds ratios (ORs) were estimated through logistic regression models adjusting for age, total energy intake and other recognized confounding factors.Subjects in the highest quartile of DII scores (i.e., with the most pro-inflammatory diets) had a higher risk of ovarian cancer compared to subjects in the lowest quartile (i.e., with an anti-inflammatory diet) (ORQuartile4vs1 1.47, 95% confidence interval, CI, 1.07, 2.01; p trend = 0.009). When analyses were carried out using continuous DII, a significant positive association with ovarian cancer was observed: the OR for one-unit increment in DII score (corresponding to approximately 8 % of its range in the current study, +6.0 to -6.20) was 1.08 (95% CI 1.02, 1.14).A pro-inflammatory diet as indicated by higher DII scores is associated with increased ovarian cancer risk.

Previous studies have reported an association between sun exposure and the increased survival of patients with cutaneous melanoma (CM). The present study analyzed the association between ultraviolet (UV) light exposure and various prognostic factors in the Italian Clinical National Melanoma Registry. Clinical and sociodemographic features were collected, as well as information concerning sunbed exposure and holidays with sun exposure. Analyses were performed to investigate the association between exposure to UV and melanoma prognostic factors. Between December 2010 and December 2013, information was obtained on 2,738 melanoma patients from 38 geographically representative Italian sites. A total of 49% of the patients were >55 years old, 51% were men, 50% lived in the north of Italy and 57% possessed a high level of education (at least high school). A total of 8 patients had a family history of melanoma and 56% had a fair phenotype (Fitzpatrick skin type I or II). Of the total patients, 29% had been diagnosed with melanoma by a dermatologist; 29% of patients presented with a very thick melanoma (Breslow thickness, >2 mm) and 25% with an ulcerated melanoma. In total, 1% of patients had distant metastases and 13% exhibited lymph node involvement. Holidays with sun exposure 5 years prior to CM diagnosis were significantly associated with positive prognostic factors, including lower Breslow thickness (P

Background: Pancreatic cancer is a leading cause of cancer death. A role of dietary factors in pancreatic carcinogenesis has been suggested. The World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) published 8 recommendations for cancer prevention. We evaluated the effect of adherence to the WCRF/AICR recommendations on pancreatic cancer risk. Methods: We operationalized 7 of the 8 WCRF/AICR recommendations to generate a WCRF/AICR score. We examined the association of WCRF/AICR score with pancreatic cancer in data from an Italian case-control study of 326 incident cases and 652 controls. Results: Adherence to WCRF/AICR recommendations was associated with a significantly decreased risk of pancreatic cancer. Using a WCRF/AICR score

Previous studies have reported that Mediterranean diet is inversely related to the risk of several neoplasms, however, limited epidemiological data are available for bladder cancer. Thus, we examined the association between Mediterranean diet and this neoplasm in an Italian multicentric case-control study consisting of 690 bladder cancer cases and 665 controls. We assessed the adherence to the Mediterranean diet via a Mediterranean Diet Score (MDS), which represents the major characteristics of the Mediterranean diet and ranges from 0 to 9 (from minimal to maximal adherence, respectively). We derived odds ratios (ORs) of bladder cancer according to the MDS score from multiple logistic regression models, allowing for major confounding factors. The ORs of bladder cancer were 0.72 (95% confidence interval, CI, 0.54&ndash, 0.98) for MDS of 4&ndash, 5 and 0.66 (95% CI, 0.47&ndash, 0.93) for MDS of 6&ndash, 9 (p for trend = 0.02) compared to MDS = 0&ndash, 3. Results were similar in strata of sex, age, and education, while the risk appeared somewhat lower in never-smokers and patients with pT1&ndash, pT4 bladder carcinomas. Among individual components of the MDS, we observed inverse associations for greater consumption of legumes, vegetables, and fish. In our study, which was carried out on an Italian population, the higher adherence to the Mediterranean diet was related to a lower risk of bladder cancer.

The Mediterranean diet has been related to a reduced risk of several common cancers but its role on breast cancer has not been quantified yet. We investigated the association between adherence to the Mediterranean diet and breast cancer risk by means of a hospital-based case-control study conducted in Italy and Switzerland. 3034 breast cancer cases and 3392 controls admitted to the same network of hospitals for acute, non-neoplastic and non-gynaecologic diseases were studied. Adherence to the Mediterranean diet was quantitatively measured through a Mediterranean Diet Score (MDS), summarizing the major characteristics of the Mediterranean dietary pattern and ranging from 0 (lowest adherence) to 9 (highest adherence). We estimated the odds ratios (ORs) of breast cancer for the MDS using multiple logistic regression models, adjusting for several covariates. Compared to a MDS of 0–3, the ORs for breast cancer were 0.86 (95% confidence interval, CI, 0.76–0.98) for a MDS of 4–5 and 0.82 (95% CI, 0.71–0.95) for a MDS of 6–9 (p for trend = 0.008). The exclusion of the ethanol component from the MDS did not materially modify the ORs (e.g., OR = 0.81, 95% CI, 0.70–0.95, for MDS ≥ 6). Results were similar in pre- and post-menopausal women. Adherence to the Mediterranean diet was associated with a reduced breast cancer risk.

Objective: To assess and quantify the association between processed meat consumption and cancers of the breast, endometrium, ovary, and prostate. Methods: Data were derived from an integrated network of hospital-based case-control studies conducted between 1982 and 2006 in various Italian areas. These studies included 5981 cases of cancer of the breast, 992 of the endometrium, 2002 of the ovary, 1582 of the prostate, and a total of 16 394 controls with data on processed meat. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional multiple logistic regression models, adjusted for major recognized confounders for each cancer site. Results: The median consumption of processed meat in this population was 2 portions per wk in each cancer-specific cases, controls, and overall, corresponding to 100 g/wk. The OR for the highest (≥20 g/d) compared with lowest (

Objectives The components of a diet can modulate inflammation and may have an effect on the development of Hodgkin's lymphoma (HL). Little is known about the inflammatory potential of diet in relation to HL. Methods Data from an Italian multicenter case-control study that was conducted between 1992 and 2008 were used to estimate the relation between a dietary inflammatory index (DII ® ) and the risk of HL. The data included 179 cases with incident, histologically confirmed HL and 186 control cases who were hospitalized for acute non-neoplastic diseases. The DII was computed on the basis of a validated, 78-item, food-frequency questionnaire. Logistic regression models were used to estimate odds ratios that were adjusted for age, sex, total energy intake, center, body mass index, years of education, tobacco use, and alcohol consumption. Results No significant association was observed between an increasing DII and the risk of HL when used either as a continuous or categorical variable. The multivariate odds ratio for the highest versus the lowest DII tertile was 1.20 (95% confidence interval: 0.71–2.04). Similarly, no positive association was observed when analyses were carried out by different strata of selected covariates. Conclusions These results do not support the hypothesis that the inflammatory potential of a diet plays a major role in the development of HL.

We assessed the association of processed meat intake with the risk of renal cell carcinoma (RCC) and bladder cancer. We used data from two Italian hospital-based case-control studies, including 1,115 RCC cases and 2,582 controls, and 1,417 bladder cancer cases and 1,732 controls. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) with unconditional logistic regression models, adjusted for major confounders. The median consumption of processed meat in cases and controls was around 2 portions/week (50 g/portion). The ORs for a daily 10 g increment of processed meat was 0.89 (95% CI 0.84-0.94) for RCC and 1.00 (95% CI 0.94-1.06) for bladder cancer. The OR for the highest vs. the lowest consumption was 0.80 (95% CI 0.66-0.96) for RCC and 0.98 (95% CI 0.80-1.21) for bladder cancer. The ORs were consistent in strata of various covariates. For bladder cancer, however, a significant 23% excess risk was found in women (95% CI 1.03-1.47) for a daily increase of 10 g, significantly heterogeneous from the risk recorded in men (OR 0.96, 95% CI 0.90-1.02). The inconsistent results between men and women and the absence of association in both sexes combined indicate that the apparent association between processed meat and bladder cancer in women is unlikely to be causal.

Endocrine disrupting chemicals (EDCs) are natural or synthetic exogenous substances affecting human health. Although present at low concentrations in the environment, they can cause a broad range of negative effects on the endocrine functions by mimicking the action of steroid hormones due to their structural similarity. Hormonal unbalance can play an important role in carcinogenesis at any stage of disease. In the case of the breast cancer, EDCs directly affect the transformation of normal breast cells into cancer cells by interfering with hormonal regulation and by inducing the alteration of factors that regulate gene expression. The principal aims of this work were to study the interaction networks of proteins modulated in breast cancer by either environmental EDCs or mycotoxins, and to identify the proteins with the strongest coordination role defined as hub nodes. Our studies evidenced the presence of seven and six hub proteins in two EDCs and mycotoxins networks, respectively. Then, by merging the two networks, we identified that three hub nodes (BCL2, ESR2 and CTNNB1) in the environmental EDCs network show direct interactions with three hub nodes (CASP8, RELA and MKI67) in the mycotoxins network. These data highlighted that two networks are linked through proteins involved in the apoptosis regulation and in processes related to cell proliferation and survival, and, thus, in breast cancer progression.

This review summarizes the main pathophysiological basis of the relationship between metabolic syndrome, endocrine disruptor exposure and prostate cancer that is the most common cancer among men in industrialized countries. Metabolic syndrome is a cluster of metabolic and hormonal factors having a central role in the initiation and recurrence of many western chronic diseases including hormonal-related cancers and it is considered as the worlds leading health problem in the coming years. Many biological factors correlate metabolic syndrome to prostate cancer and this review is aimed to focus, principally, on growth factors, cytokines, adipokines, central obesity, endocrine abnormalities and exposure to specific endocrine disruptors, a cluster of chemicals, to which we are daily exposed, with a hormone-like structure influencing oncogenes, tumor suppressors and proteins with a key role in metabolism, cell survival and chemo-resistance of prostate cancer cells. Finally, this review will analyze, from a molecular point of view, how specific foods could reduce the relative risk of incidence and recurrence of prostate cancer or inhibit the biological effects of endocrine disruptors on prostate cancer cells. On the basis of these considerations, prostate cancer remains a great health problem in terms of incidence and prevalence and interventional studies based on the treatment of metabolic syndrome in cancer patients, minimizing exposure to endocrine disruptors, could be a key point in the overall management of this disease.

BACKGROUND: Some components of the Mediterranean diet have favourable effects on endometrial cancer, and the Mediterranean diet as a whole has been shown to have a beneficial role on various neoplasms. METHODS: We analysed this issue pooling data from three case-control studies carried out between 1983 and 2006 in various Italian areas and in the Swiss Canton of Vaud. Cases were 1411 women with incident, histologically confirmed endometrial cancer, and controls were 3668 patients in hospital for acute diseases. We measured the adherence to the Mediterranean diet using a Mediterranean Diet Score (MDS), based on the nine dietary components characteristics of this diet, that is, high intake of vegetables, fruits/nuts, cereals, legumes, fish; low intake of dairy products and meat; high monounsaturated to saturated fatty acid ratio; and moderate alcohol intake. We estimated the odds ratios (OR) and the corresponding 95% confidence intervals (CI) for increasing levels of the MDS (varying from 0, no adherence, to 9, maximum adherence) using multiple logistic regression models, adjusted for major confounding factors. RESULTS: The adjusted OR for a 6-9 components of the MDS (high adherence) compared with 0-3 (low adherence) was 0.43 (95% CI 0.34-0.56). The OR for an increment of one component of MDS diet was 0.84 (95% CI 0.80-0.88). The association was consistent in strata of various covariates, although somewhat stronger in older women, in never oral contraceptive users and in hormone-replacement therapy users. CONCLUSIONS: Our study provides evidence for a beneficial role of the Mediterranean diet on endometrial cancer risk, suggesting a favourable effect of a combination of foods rich in antioxidants, fibres, phytochemicals, and unsaturated fatty acids.

Genomic and trascriptomic profiling has recently contributed details to the characterization of luminal B breast cancer. We explored the contribution of anthropometric, metabolic, and molecular determinants to the multifaceted heterogeneity of this breast cancer subtype, with a specific focus on the association between body mass index (BMI), pre-treatment fasting glucose, hormone receptors, and expression of human epidermal growth factor receptor 2 (HER2). Extensively annotated specimens were obtained from 154 women with luminal B breast cancer diagnosed at two Italian comprehensive cancer centres. Participants' characteristics were descriptively analyzed overall and by HER2 status (positive vs. negative). BMI (

Background Scanty data exist on the role of personal medical conditions, except for gallstones, and family history of cancer on the risk of biliary tract cancers (BTC). Methods We analyzed this issue using data from two Italian case-control studies, including 159 cases of BTC and 795 matched hospital controls. Odds ratios (ORs) of BTC and corresponding 95% confidence intervals (CIs) were estimated using multiple logistic regression models. Results Gallstones were associated with a 2-fold excess risk of BTC (95% CI 1.24-3.45). No significant associations were observed with other conditions investigated, including diabetes (OR 1.15, 95% CI 0.63-2.11), hypertension (OR 0.65, 95% CI 0.39-1.11), hyperlipidemia (OR 0.61, 95% CI 0.31-1.21), allergy (OR 0.64, 95% CI 0.29-1.40), gastroduodenal ulcer (OR 0.52, 95% CI 0.24-1.12), hepatitis (OR 2.02, 95% CI 0.35-11.67), benign thyroid diseases (OR 1.16, 95% CI 0.56-2.40), hysterectomy (OR 1.19, 95% CI 0.53-2.68), unilateral oophorectomy (OR 1.75, 95% CI 0.44-6.93), and bilateral oophorectomy (OR 2.48, 95% CI 0.79-7.82). We found an excess risk of BTC in relation to family history of any cancer (OR 1.52, 95% CI 1.03-2.24) and family history of gallbladder cancer (OR 3.83, 95% CI 0.59-24.75). Conclusions The present study confirms a strong association between BTC and history of gallstones, and provides further evidence of a positive association with family history of cancer.

Diet has been suggested to have a role on endometrial cancer risk, but few data are available on the role of dietary patterns on this neoplasm. A case–control study was carried out in Italy, including 454 women with endometrial cancer and 908 hospital controls admitted to the same hospitals for acute, non-neoplastic diseases. Dietary information was based on a reproducible and valid food frequency questionnaire. A posteriori dietary patterns were obtained using principal component factor analysis on 28 nutrients. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were obtained from multiple logistic regression models conditioned on age and study center, and adjusted for major known confounding factors. Positive associations were found for the “Western-type diet” (OR = 1.63, 95% CI: 1.12–2.38, for the highest versus the lowest quartile category) and the “Animal-derived nutrients and polyunsaturated fatty acids” patterns (OR = 1.76, 95% CI: 1.23–2.52). The corresponding risk estimates among women with a body mass index ≥30 were 2.08 (95% CI: 0.92–4.69) and 2.30 (95% CI: 1.03–5.16) for the two patterns, respectively. No association was found for the other three patterns (i.e., “Vitamins and fiber”, OR = 0.96, 95% CI: 0.67–1.37, “Starch-rich”, OR = 0.99, 95% CI: 0.69–1.42, and “Other fats”, OR = 1.03, 95% CI: 0.70–1.52). This study indicates that dietary habits characterized by high intakes of animal products increase endometrial cancer risk, the association being appreciably stronger for obese women.

// Giuseppe Buono 1, * , Anna Crispo 2, * , Mario Giuliano 1, 3 , Carmine De Angelis 1 , Francesco Schettini 1 , Valeria Forestieri 1 , Rossella Lauria 1 , Matilde Pensabene 1 , Michelino De Laurentiis 4 , Livia Silvia Adriana Augustin 2, 5 , Alfonso Amore 4 , Massimiliano D’Aiuto 4 , Raffaele Tortoriello 4 , Antonello Accurso 6 , Ernesta Cavalcanti 2 , Gerardo Botti 2 , Maurizio Montella 2 , Sabino De Placido 1 and Grazia Arpino 1 1 Department of Clinical Medicine and Surgery, Oncology Division, University of Naples Federico II, Naples, Italy 2 Unit of Epidemiology, National Cancer Institute, G. Pascale Foundation, Naples, Italy 3 Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA 4 Breast Unit, National Cancer Institute, G. Pascale Foundation, Naples, Italy 5 Clinical Nutrition and Risk Factor Modification Centre, St. Michael’s Hospital, Toronto, Canada 6 Department of Gastroenterology, Endocrinology and Surgery, University of Naples Federico II, Naples, Italy * These authors contributed equally to this work Correspondence to: Grazia Arpino, email: grazia.arpino@unina.it Keywords: breast cancer; obesity; diabetes; combined variables; outcome Received: August 19, 2017 Accepted: November 16, 2017 Published: December 05, 2017 ABSTRACT Background: Previous studies suggested that obesity and diabetes were correlated with breast cancer outcome. The aim of the present study was to investigate the prognostic effect of obesity and diabetes on the outcome of early breast cancer patients. Materials and Methods: Overall, 841 early breast cancer patients were prospectively enrolled between January 2009 and December 2013. Study population was divided into four groups: (1) patients without obesity or diabetes; (2) patients with only diabetes; (3) patients with only obesity; and (4) patients with both diabetes and obesity. Categorical variables were analyzed by the chi-square test and survival data by the log-rank test. Results: At diagnosis, obese and diabetic patients were more likely to be older ( p < 0.0001) and post-menopausal ( p < 0.0001) and to have a tumor larger than 2 cm ( p < 0.0001) than patients in groups 1–3. At univariate analyses, obese and diabetic patients had a worse disease-free survival ( p = 0.01) and overall survival ( p = 0.001) than did patients without obesity and diabetes. At multivariate analyses, the co-presence of obesity and diabetes was an independent prognostic factor for disease-free survival (hazard ratio=2.62, 95% CI 1.23–5.60) but not for overall survival. Conclusions: At diagnosis, patients with obesity and diabetes were older, had larger tumors and a worse outcome compared to patients without obesity or diabetes. These data suggest that metabolic health influences the prognosis of patients affected by early breast cancer.

Prostate cancer is one of the most difficult cancers to treat especially when it becomes hormone resistant such as castrate resistant prostate cancer (CRPC) and subsequent metastatic CRPC. Apart from the genetic alterations in prostate cancer, epigenetic modifications also play an important role in the development and neoplastic progression of this disease. These include DNA methylation, histone modifications, and non-coding microRNAs. miRNAs are a novel class of small endogenous single-stranded non-coding RNAs of 19-25 nucleotides in length that typically silence gene expression. Considering the reversibility of epigenetic alterations in early carcinogenesis process, reversion (correction) of these modifications by green tea catechins could be a promising strategy for cancer chemoprevention and therapy. Recent evidence suggests that green tea catechins such as epigallocatechin gallate (EGCG) not only act as epigenetic modulators but can also modify miRNA expression and their target mRNAs, consistently contributing to the inhibition of prostate carcinogenesis. Various studies also indicate that several green tea polyphenols (GTPs) exert synergistic effects with other cancer chemotherapeutic agents. Therefore, the use of appropriate combinations of green tea catechins with the existing chemotherapeutics will lead to a reduction in side effects without decreasing the chemotherapeutic effects. This review will summarize the key results from recent studies detailing the effects of green tea catechins such as EGCG on epigenetic alterations and miRNA expression in prostate cancer.

Proanthocyanidins are polymers of monomeric unit flavan-3-ols with antioxidant, anti-inflammatory and free radical scavenging activities. We investigated the association between proanthocyanidin intake and prostate cancer risk through data that were collected between 1991 and 2002 in an Italian case–control study, including a total of 1,294 incident, histologically confirmed cases of prostate cancer and 1,451 controls admitted to hospital for acute, non-neoplastic, and non-hormone-related diseases. We estimated odds ratios (ORs) and their 95% confidence intervals (CIs) using multiple logistic regression models, and computed energy-adjusted proanthocyanidin intakes using the residual method. The ORs for the highest versus the lowest tertile were 0.80 (95% CI 0.83–1.00) for energy-adjusted monomers and dimers combined, 0.72 (95% CI 0.59–0.87) for polymers with ≥ 3 mers, and 0.72 (95% CI 0.59–0.88) for total proanthocyanidins. The inverse relation was stronger among cases with a Gleason score ≥ 7, with the ORs of 0.56 (95% CI 0.40–0.78) for monomers and dimers, 0.62 (95% CI 0.40–0.78) for polymers with ≥ 3 mers, and 0.57 (95% CI 0.42–0.77) for total proanthocyanidins. These risk estimates were consistent across strata of age, education, body mass index, and family history of prostate cancer. Our data indicate an inverse association between proanthocyanidins and prostate cancer risk.

To add evidence to the limited data available from southern Europe, we assessed the association between processed meat consumption and colorectal cancer risk. We analyzed data from three case-control studies conducted between 1985 and 2010 in various Italian areas, including a total of 3745 incident cases and 6804 hospital-based controls. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) by unconditional multiple logistic regression models. The median consumption of processed meat was around 20 g/day both in cases and controls. The OR of colorectal cancer was 1.02 (95% CI 0.99-1.04) for an increase of 10 g/day of processed meat. The association was statistically significant for colon cancer (OR 1.03, 95% CI 1.00-1.06), particularly for proximal colon cancer (OR 1.09, 95% CI 1.04-1.14), while there was no relation with rectal cancer (OR 0.99, 95% CI 0.95-1.03). The OR of proximal colon cancer was 1.38 (95% CI 1.08-1.75) for the highest sex-specific tertile of consumption (>25 g/day for men, >21.5 for women) compared with the lowest (

Network analysis is a useful approach in cancer biology as it provides information regarding the genes and proteins. In our previous study, a network analysis was performed on dysregulated genes in HepG2 cells, a hepatoblastoma cell line that lacks the viral infection, compared with normal hepatocytes, identifying the presence of 26 HUB genes. The present study aimed to identify whether these previously identified HUB genes participate in the network that controls the human circadian rhythms. The results of the present study demonstrated that 20/26 HUB genes were associated with the metabolic processes that control human circadian rhythms, which supports the hypothesis that a number of cancer types are dependent from circadian cycles. In addition, it was revealed that the CLOCK circadian regulator gene was associated, via cytoskeleton associated protein 5 (CKAP5), with the HUB genes of the HepG2 network, and that CKAP5 was associated with three other circadian genes (casein kinase 1e, casein kinase 1δ and histone deacetylase 4) and 10 HepG2 genes (SH2 domain containing, ZW10 interacting kinetochore protein, aurora kinase B, cell division cycle 20, centromere protein A, inner centromere protein, mitotic arrest deficient 2 like 1, baculoviral IAP repeat containing 5, SPC24 NDC80 kinetochore complex component and kinesin family member 2C). Furthermore, the genes that associate the circadian system with liver cancer were demonstrated to encode intrinsically disordered proteins. Finally, the results of the present study identified the microRNAs involved in the network formed by the overlapping of HepG2 and circadian genes.

// Andrea Polo 1 , Anna Crispo 1 , Pellegrino Cerino 2 , Luca Falzone 3 , Saverio Candido 3 , Aldo Giudice 1 , Giuseppina De Petro 4 , Gennaro Ciliberto 5 , Maurizio Montella 1 , Alfredo Budillon 6 and Susan Costantini 6 1 Epidemiology Unit, Istituto Nazionale Tumori “Fondazione G. Pascale”, IRCCS, Napoli, Italia 2 Istituto Zooprofilattico Sperimentale del Mezzogiorno (IZSM), Napoli, Italia 3 Department of Biomedical and Biotechnological Sciences, Section of General and Clinical Pathology and Oncology – Translational Oncology and Functional Genomics Laboratory, University of Catania, Catania, Italy 4 Dipartimento di Medicina Molecolare e Traslazionale, Universita di Brescia, Brescia, Italia 5 Scientific Directorate, Istituto Nazionale Tumori “Regina Elena”, IRCCS, Roma, Italia 6 Experimental Pharmacology Unit, Istituto Nazionale Tumori “Fondazione G. Pascale”, IRCCS, Napoli, Italia Correspondence to: Alfredo Budillon, email: a.budillon@istitutotumori.na.it Susan Costantini, email: s.costantini@istitutotumori.na.it Keywords: bladder cancer, network analysis, environmental exposure, arsenicals Received: March 16, 2017 Accepted: April 12, 2017 Published: May 26, 2017 ABSTRACT Bladder cancer (BC) is the 9th most common cancer worldwide, and the 6th most common cancer in men. Its development is linked to chronic inflammation, genetic susceptibility, smoking, occupational exposures and environmental pollutants. Aim of this work was to identify a sub-network of genes/proteins modulated by environmental or arsenic exposure in BC by computational network approaches. Our studies evidenced the presence of HUB nodes both in “BC and environment” and “BC and arsenicals” networks. These HUB nodes resulted to be correlated to circadian genes and targeted by some miRNAs already reported as involved in BC, thus suggesting how they play an important role in BC development due to environmental or arsenic exposure. Through data-mining analysis related to putative effect of the identified HUB nodes on survival we identified genes/proteins and their mutations on which it will be useful to focus further experimental studies related to the evaluation of their expression in biological matrices and to their utility as biomarkers of BC development.

Background Mechanisms influencing breast cancer (BC) development and recurrence include hyperglycemia, hyperinsulinemia, high insulin-like growth factor-1, high circulating estrogen, inflammation and impaired cellular differentiation/apoptosis. A lifestyle program that targets all the above mechanisms may be warranted. Low glycemic index (GI) foods produce lower post-prandial glucose and insulin responses and have been associated with lower BC risk. Moderate physical activity post-diagnosis reduces BC recurrence and mortality, partly explained by reduced insulin and estrogen levels. Vitamin D increases cell differentiation/apoptosis and high serum vitamin D levels improve BC survival. Yet no trial has evaluated the combined effect of a low GI diet, moderate physical activity and vitamin D supplementation on BC recurrence in the context of a Mediterranean lifestyle setting. Methods Women (30-74 yr) who had undergone surgery for primary histologically confirmed BC (stages I-III) within the previous 12 months, in cancer centres in Italy, will be randomized to follow, for a maximum of 33 months, either a high intensity treatment (HIT) composed of low GI diet + exercise + vitamin D (60 ng/mL serum concentration) or a lower intensity treatment (LITE) with general advice to follow a healthy diet and exercise pattern + vitamin D to avoid insufficiency. Both interventions are on a background of a Mediterranean diet. Considering a 20% recurrence rate within 3 years for BC cases and a predicted rate of 10% in the HIT group, with power of 80% and two-sided alpha of 0.05, the subject number required will be 506 (n = 253 in each arm). Clinic visits will be scheduled every 3 months. Dietary and exercise counselling and vitamin D supplements will be given at each clinic visit when blood samples, anthropometric measures and 7-day food records will be collected. Discussion DEDiCa study aims to reduce BC recurrence in women with BC using a lifestyle approach with additional vitamin D and to investigate possible cardio-metabolic benefits as well as epigenetic modifications according to lifestyle changes. Given the supporting evidence and safety of the components of our intervention we believe it is feasible and urgent to test it in cancer patients. Trial registration May 11, 2016; NCT02786875. EudraCT Number 2015-005147-14