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Background Emerging reports suggest that new onset of smell or taste loss are potential early clinical markers of SARS-CoV-2 infection, but it remains unclear as to what extent. Therefore, the purpose of this study is to systematically assess the prevalence of self-reported altered sense of smell or taste in patients with confirmed SARS-CoV-2 infection, overcoming the limitations of individual studies by meta-analysis of pooled data. Methods The databases Medline, Embase, Web of Science, Scopus and MedRxiv's set were searched from inception to the 4th May 2020. This study was conducted following the PRISMA checklist. Results 18 studies met the eligibility criteria out of the 171 initially screened citations. The overall prevalence of alteration of the sense of smell or taste was 47% , but estimates were 31% and 67% in severe and mild-to-moderate symptomatic patients, respec- tively. The loss of smell and taste preceded other symptoms in 20% of cases and it was concomitant in 28%. Conclusions Based on this meta-analysis, we recommend self-isolation and testing, where possible, for patients complaining smell or taste impairment during COVID-19 pandemic in order to prevent spread of disease and propose the inclusion of loss of smell and taste as recognized symptoms of SARS-CoV-2 in the World Health Organization and other relevant regulatory body's lists.

Reaction of condensation and cross-linking of catechin monomer as a model of condensed (flavonoid) tannin extracts and of mimosa tannin itself, as well as of resorcinol with triethyl phosphate (TEP) have been investigated. FTIR, solid state CP-MAS 13 C NMR, 31 P NMR and MALDI-ToF spectroscopy studies revealed that reaction occurs mainly on the C3 of the flavonoid heterocycle ring and on the aromatic C4′ and C5′ carbons of the flavonoids B-ring, while TEP does not appear to react on the A-ring. A difference in the relative proportions of these two reaction sites for tannin and catechin has been noticed. The reactions appear to be dependent on the temperature. According to the thermogravimetric analysis, materials obtained from the reaction of tannin with TEP showed high thermal stability.

// Nicole M. Davis 1 , Melissa Sokolosky 1 , Kristin Stadelman 1 , Stephen L. Abrams 1 , Massimo Libra 2 , Saverio Candido 2 , Ferdinando Nicoletti 2 , Jerry Polesel 3 , Roberta Maestro 4 , Antonino D’Assoro 5 , Lyudmyla Drobot 6 , Dariusz Rakus 7 , Agnieszka Gizak 7 , Piotr Laidler 8 , Joanna Dulinska-Litewka 8 , Joerg Basecke 9 , Sanja Mijatovic 10 , Danijela Maksimovic-Ivanic 10 , Giuseppe Montalto 11,12 , Melchiorre Cervello 12 , Timothy L. Fitzgerald 13 , Zoya N. Demidenko 14 , Alberto M. Martelli 15 , Lucio Cocco 15 , Linda S. Steelman 1 and James A. McCubrey 1 1 Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University Greenville, NC 27858 USA 2 Department of Bio-Medical Sciences, University of Catania, Catania, Italy 3 Unit of Epidemiology and Biostatistics, Centro di Riferimento Oncologico, IRCCS, Aviano, Italy 4 Experimental Oncology 1, CRO IRCCS, National Cancer Institute, Aviano, Pordenone, Italy 5 Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA 6 Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine 7 Department of Animal Molecular Physiology, Institute of Experimental Biology, Wroclaw University, Wroclaw, Poland 8 Chair of Medical Biochemistry, Jagiellonian University Medical College, Krakow, Poland 9 Department of Medicine University of Gottingen, Gottingen, Germany 10 Department of Immunology, Institute for Biological Research “Sinisa Stankovic” University of Belgrade, Belgrade, Serbia 11 Biomedical Department of Internal Medicine and Specialties, University of Palermo, Palermo, Italy 12 Consiglio Nazionale delle Ricerche,Istituto di Biomedicina e Immunologia Molecolare “Alberto Monroy”, Palermo, Italy 13 Department of Surgery, Brody School of Medicine at East Carolina University, Greenville, NC 14 Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA 15 Dipartimento di Scienze Biomediche e Neuromotorie, Universita di Bologna, Bologna, Italy Correspondence: James A. McCubrey, email: // Keywords : Targeted Therapy, Therapy Resistance, Mutations, PI3K, mTOR, rapamycin Received : June 04, 2014 Accepted : July 11, 2014 Published : July 12, 2014 Abstract The EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway plays prominent roles in malignant transformation, prevention of apoptosis, drug resistance and metastasis. The expression of this pathway is frequently altered in breast cancer due to mutations at or aberrant expression of: HER2 , ER alpha, BRCA1, BRCA2, EGFR1 , PIK3CA , PTEN , TP53 , RB as well as other oncogenes and tumor suppressor genes. In some breast cancer cases, mutations at certain components of this pathway ( e.g. , PIK3CA ) are associated with a better prognosis than breast cancers lacking these mutations. The expression of this pathway and upstream HER2 has been associated with breast cancer initiating cells (CICs) and in some cases resistance to treatment. The anti-diabetes drug metformin can suppress the growth of breast CICs and herceptin-resistant HER2+ cells. This review will discuss the importance of the EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway primarily in breast cancer but will also include relevant examples from other cancer types. The targeting of this pathway will be discussed as well as clinical trials with novel small molecule inhibitors. The targeting of the hormone receptor, HER2 and EGFR1 in breast cancer will be reviewed in association with suppression of the EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway.

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

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.

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.

Background A family history of bladder cancer has been associated with the risk of bladder cancer, but quantification of the excess risk in different populations is still a relevant issue. Further, the role of a family history of other cancers on the risk of bladder cancer remains unclear. Methods We analyzed data from an Italian case–control study, including 690 bladder cancer cases and 665 hospital controls. Odds ratios (ORs) were estimated through unconditional logistic regression models, adjusted for sex, age, study center, year of interview and further for education, smoking and sibling's number. Results The OR for family history of bladder cancer was 2.13 (95% confidence intervals (95%CIs) 1.02–4.49) from the model with partial adjustment, and 1.99 (95%CI 0.91–4.32) after additional adjustment for smoking and siblings' number, based on 23 cases (3.3%) and 11 controls (1.7%) with a family history of bladder cancer. The fully adjusted OR was 3.77 when the relative was diagnosed at age below 65years. Smokers with a family history of bladder cancer had a four-fold increased risk compared to non-smokers without a family history. Bladder cancer risk was significantly increased among subjects with a family history of hemolymphopoietic cancers (OR=2.97, 95%CI 1.35–6.55). Family history of cancer at other sites showed no significant association with bladder cancer risk. Conclusion This study confirms an approximately two-fold increased risk of bladder cancer for family history of bladder cancer, and indicates a possible familial clustering of bladder cancer with cancers of the hemolymphopoietic system.

Purpose: Few studies investigated the role of diet on nasopharyngeal cancer (NPC) risk in non-endemic areas. The aim of this study was to assess the association between adherence to the traditional Mediterranean diet and NPC risk in a southern European low-risk population. Methods: We conducted a hospital-based case-control study in Italy, including 198 histologically confirmed NPC cases and 594 matched controls. Dietary habits were collected by means of a validated food-frequency questionnaire, including 83 foods, food groups, or beverages. Adherence to the traditional Mediterranean diet was assessed through a Mediterranean Diet Score (MDS), based on nine dietary components characterizing this dietary profile, i.e., high intake of vegetables, fruits and nuts, cereals, legumes, and fish; low intake of dairy products and meat; high monounsaturated to saturated fatty acid ratio; and moderate alcohol intake. We estimated odds ratios (ORs) of NPC, and the corresponding 95% confidence intervals (CIs), for increasing MDS (i.e., increasing adherence) using multiple logistic regression models, adjusted for major confounding factors. Results: As compared to MDS ≤ 4, the ORs of NPC were 0.83 (95% CI: 0.54–1.25) for MDS of 5 and 0.66 (95% CI: 0.44–0.99) for MDS ≥ 6, with a significant trend of decreasing risk (p 0.043). The corresponding population attributable fraction was 22%, indicating that 22% of NPC cases in this population would be avoided by shifting all subjects to a score ≥6. Conclusions: Our study supports a favorable role of the Mediterranean diet on NPC risk.

BACKGROUND: The risk of many cancers is higher in subjects with a family history (FH) of cancer at a concordant site. However, few studies investigated FH of cancer at discordant sites. PATIENTS AND METHODS: This study is based on a network of Italian and Swiss case-control studies on 13 cancer sites conducted between 1991 and 2009, and including more than 12 000 cases and 11 000 controls. We collected information on history of any cancer in first degree relatives, and age at diagnosis. Odds ratios (ORs) for FH were calculated by multiple logistic regression models, adjusted for major confounding factors. RESULTS: All sites showed an excess risk in relation to FH of cancer at the same site. Increased risks were also found for oral and pharyngeal cancer and FH of laryngeal cancer (OR = 3.3), esophageal cancer and FH of oral and pharyngeal cancer (OR = 4.1), breast cancer and FH of colorectal cancer (OR = 1.5) and of hemolymphopoietic cancers (OR = 1.7), ovarian cancer and FH of breast cancer (OR = 2.3), and prostate cancer and FH of bladder cancer (OR = 3.4). For most cancer sites, the association with FH was stronger when the proband was affected at age

Purpose: We investigated risk factors for colorectal cancer in early-onset cancers, to provide quantitative estimates for major selected risk factors. Methods: We analyzed data from three Italian and Swiss case-control studies conducted between 1985 and 2009, including 329 colorectal cancer cases and 1,361 controls aged ≤45 years. We computed odds ratios (ORs) from unconditional logistic regression models, adjusted for major confounding factors. Results: The OR of young-onset colorectal cancer was 4.50 for family history of colorectal cancer in first-degree relatives, the association being higher in subjects with affected siblings (OR 11.68) than parents (OR 3.75). The ORs of young-onset colorectal cancer were 1.56 for ≥14 drinks/week of alcohol, 1.56 for the highest tertile of processed meat, 0.40 for vegetables, 0.75 for fruit, and 0.78 for fish intake. Among micronutrients, the ORs were 0.52 for β-carotene, 0.68 for vitamin C, 0.38 for vitamin E, and 0.59 for folate. No significant associations emerged for physical activity, overweight, and diabetes. Conclusions: This study - the largest on young-onset colorectal cancer - confirms that several recognized risk factors for colorectal cancer are also relevant determinants of young-onset colorectal cancer. Family history of colorectal cancer in particular is a stronger risk factor in young subjects, as compared to middle age and elderly ones.

BACKGROUND: Dietary habits have been related to the risk of nasopharyngeal carcinoma (NPC), but information on a wide range of macro- and micronutrients is still lacking, particularly for low-incidence countries. METHODS: We conducted a hospital-based case-control study in Italy on 198, histologically confirmed, NPC cases of Caucasian ethnicity of 18-76 years of age. Controls were 594 Caucasian cancer-free patients admitted to general hospitals for acute conditions. Nutrients intake was assessed through a validated food-frequency questionnaire. Adjusted odds ratios (ORs) and the corresponding confidence intervals (CIs) were estimated through logistic regression. RESULTS: Dietary intake of carotenoids were inversely related to NPC risk, notably carotene (OR for highest vs lowest quartile=0.46; 95% CI: 0.26-0.79), α-carotene (OR=0.57; 95% CI: 0.33-0.97), and β-carotene (OR=0.42; 95% CI: 0.24-0.75). Increased NPC risk was observed for elevate cholesterol intake (OR=1.85; 95% CI: 1.12-3.05). CONCLUSION: Study findings suggest a protective effect of carotenoids against NPC in a low-risk population, adding further support to a possible beneficial role of a diet rich in fruits and vegetables in cancers of the head and neck.

Background Scanty and inconsistent studies are available on the relation between dietary fiber intake and pancreatic cancer. A case–control study was carried out in northern Italy to further investigate the role of various types of dietary fibers in the etiology of pancreatic cancer. Patients and methods Cases were 326 patients with incident pancreatic cancer, excluding neuroendocrine tumors, admitted to major teaching and general hospitals during 1991–2008. Controls were 652 patients admitted for acute, nonneoplastic conditions to the same hospital network of cases. Information was elicited using a validated food frequency questionnaire. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for intake quintiles of different types of fiber after allowance for total energy intake and other potential confounding factors. Results Total fiber intake was inversely related to risk of pancreatic cancer (OR = 0.4 for highest versus lowest quintile of intake; 95% CI 0.2–0.7). An inverse association emerged between pancreatic cancer and both soluble (OR = 0.4; 95% CI 0.2–0.7) and total insoluble fiber (OR = 0.5; 95% CI 0.3–0.8), particularly cellulose (OR = 0.4; 95% CI 0.3–0.7) and lignin (OR = 0.5; 95% CI 0.3–0.9). Fruit fiber intake was inversely associated with pancreatic cancer (OR = 0.5; 95% CI 0.3–0.8), whereas grain fiber was not (OR = 1.2; 95% CI 0.7–2.0). Conclusions This study suggests that selected types of fiber and total fiber are inversely related to pancreatic cancer.

PURPOSE: Carbohydrates and dietary glycemic index (GI) influence the secretion of insulin and insulin-related growth factors and may play a role in the development of diabetes and obesity, both of which have been related to pancreatic cancer risk. METHODS: We examined the association between dietary GI and glycemic load (GL) and pancreatic cancer by conducting a hospital-based case-control study in Italy in 1991-2008 of 326 cases of pancreatic cancer and 652 control patients. Dietary data were obtained with the use of a validated food-frequency questionnaire. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were computed with the use of multiple logistic regression. RESULTS: GI was positively associated with pancreatic cancer, with ORs of 1.56 (95% CI, 1.06-2.30) and 1.78 (95% CI, 1.20-2.62) for the second and third tertiles, respectively, compared with the lowest. No significant association was observed between GL and pancreatic cancer. Consumption of sugar, candy, honey, and jam was positively associated with pancreatic cancer, whereas consumption of fruit was inversely associated. CONCLUSIONS: In conclusion, the positive association with high GI, in the absence of an association with dietary GL, fruit, or total carbohydrates, likely reflects the positive association between sweets or refined carbohydrates and pancreatic cancer in this study population. Ann Epidemiol 2010;20:460-465. (c) 2010 Elsevier Inc. All rights reserved.

A role of diet and nutrition in pancreatic carcinogenesis has been suggested, but the association between selected macronutrients, fatty acids, cholesterol and pancreatic cancer remains controversial. We analysed data from a hospital-based case-control study conducted in Italy between 1991 and 2008, including 326 cases (174 men and 152 women) with incident pancreatic cancer, and 652 controls (348 men and 304 women) frequency-matched to cases by sex, age and study Centre. Odds ratios (ORs) and 95% confidence intervals (Cls) were estimated using multiple logistic regression models conditioned oil age, sex and study centre, and adjusted for year of interview, education, tobacco smoking, history of diabetes and energy intake. A positive association was found for animal proteins (OR = 1.85 for the highest versus the lowest quintile of intake; 95% CI: 1.15-2.96; p for trend = 0.039), whereas a negative association was observed for sugars (OR = 0.52; 95% CI: 0.31-0.86; p for trend = 0.003). Non-significant negative associations emerged for vegetable proteins (OR = 0.69) and polyunsaturated fatty acids (OR = 0.67). In conclusion, a diet poor in animal proteins and rich in sugars (mainly derived from fruit) appears to have a beneficial effect on pancreatic cancer risk. (C) 2009 Elsevier Ltd. All rights reserved.

The objective of this study is to investigate the effect of menstrual and reproductive variables, breastfeeding, exogenous hormones, and gynecological conditions on endometrial cancer risk. We conducted a case-control study in Italy, including 454 women with endometrial cancer and 908 hospital controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariate logistic regression models. Endometrial cancer risk was inversely associated with age at menarche (OR = 0.7, 95% CI = 0.5-1.0, for > or =14 vs. or =55 vs. or =3 deliveries vs.

Background:The Mediterranean diet has been shown to have a beneficial role on various neoplasms, but data are scanty on pancreatic cancer.Methods:We analysed data from two case-control studies conducted in Italy between 1983 and 2008, including 362 and 326 pancreatic cancer cases and 1552 and 652 hospital-controls, respectively. A Mediterranean Diet Score (MDS) summarising major characteristics of the Mediterranean diet was used in the two studies separately and overall. Two further scores of adherence to the Mediterranean diet were applied in the second study only, the Mediterranean Dietary Pattern Adherence Index (MDP) and the Mediterranean Adequacy Index (MAI).Results:Odds ratios (ORs) for increasing levels of the scores (i.e., increasing adherence) were estimated using multiple logistic regression models. Odds ratio for a MDS score >/=6 compared with

Background Consumption of red meat has been related to increased risk of several cancers. Cooking methods could modify the magnitude of this association, as production of chemicals depends on the temperature and duration of cooking. Methods We analyzed data from a network of case–control studies conducted in Italy and Switzerland between 1991 and 2009. The studies included 1465 oral and pharyngeal, 198 nasopharyngeal, 851 laryngeal, 505 esophageal, 230 stomach, 1463 colon, 927 rectal, 326 pancreatic, 3034 breast, 454 endometrial, 1031 ovarian, 1294 prostate and 767 renal cancer cases. Controls included 11 656 patients admitted for acute, non-neoplastic conditions. Odds ratios (ORs) and confidence intervals (CIs) were estimated by multiple logistic regression models, adjusted for known confounding factors. Results Daily intake of red meat was significantly associated with the risk of cancer of the oral cavity and pharynx (OR for increase of 50 g/day = 1.38; 95% CI: 1.26–1.52), nasopharynx (OR = 1.29; 95% CI: 1.04–1.60), larynx (OR = 1.46; 95% CI: 1.30–1.64), esophagus (OR = 1.46; 95% CI: 1.23–1.72), colon (OR = 1.17; 95% CI: 1.08–1.26), rectum (OR = 1.22; 95% CI:1.11–1.33), pancreas (OR = 1.51; 95% CI: 1.25–1.82), breast (OR = 1.12; 95% CI: 1.04–1.19), endometrium (OR = 1.30; 95% CI: 1.10–1.55) and ovary (OR = 1.29; 95% CI: 1.16–1.43). Fried meat was associated with a higher risk of cancer of oral cavity and pharynx (OR = 2.80; 95% CI: 2.02–3.89) and esophagus (OR = 4.52; 95% CI: 2.50–8.18). Risk of prostate cancer increased for meat cooked by roasting/grilling (OR = 1.31; 95% CI: 1.12–1.54). No heterogeneity according to cooking methods emerged for other cancers. Nonetheless, significant associations with boiled/stewed meat also emerged for cancer of the nasopharynx (OR = 1.97; 95% CI: 1.30–3.00) and stomach (OR = 1.86; 95% CI: 1.20–2.87). Conclusions Our analysis confirmed red meat consumption as a risk factor for several cancer sites, with a limited impact of cooking methods. These findings, thus, call for a limitation of its consumption in populations of Western countries.

PURPOSE: The role of dietary habits in the etiology of nasopharyngeal carcinoma (NPC) has been extensively investigated in high-incidence areas, but evidence is scanty in low-incidence populations. This study aimed to investigate the relationship between NPC risk and a wide range of food groups in the Italian population. METHODS: We conducted a hospital-based case-control study in Italy on 198, histologically confirmed, NPC cases of Caucasian ethnicity, aged 18-76 years. Controls were 594 Caucasian cancer-free patients admitted to general hospitals for acute conditions. Odds ratios (ORs) and the corresponding confidence intervals (CIs) were estimated through logistic regression, adjusting for socio-demographic characteristics, tobacco smoking, alcohol drinking, and energy intake. RESULTS: Elevated vegetable consumption was inversely related to NPC risk (OR for highest vs. lower quartile = 0.51; 95 % CI 0.29-0.90). The association was particularly strong for yellow- or red-pigmented vegetables (OR = 0.31; 95 % CI 0.18-0.54), and this effect was stronger among never smokers (OR = 0.18; 95 % CI 0.06-0.55) than among ever smokers (OR = 0.37; 95 % CI 0.19-0.71). Increased NPC risk emerged for elevated eggs consumption (OR = 2.50; 95 % CI 1.44-4.32; p-trend

A favorable role of fruit and vegetables on colorectal cancer risk has been related to the antioxidant properties of their components. We used data from an Italian case-control study including 1,953 patients with incident, histologically confirmed colorectal cancer (1,225 colon and 728 rectal cancers). Controls were 4,154 patients admitted to hospital for acute, non-neoplastic conditions. A reproducible and valid food frequency questionnaire was used to assess subjects' usual diet. Total antioxidant capacity (TAC) was measured using Italian food composition tables in terms of ferric reducing-antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC) and total radical-trapping antioxidant parameter (TRAP). We estimated the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) through multiple logistic regression models, including terms for potential confounding factors, and energy intake. TAC was inversely related with colorectal cancer risk: the OR for the highest versus the lowest quintile was 0.68 (95% CI, 0.57-0.82) for FRAP, 0.69 (95% CI, 0.57-0.83) for TEAC and 0.69 (95% CI, 0.57-0.83) for TRAP. Corresponding values, excluding TAC deriving from coffee, were 0.75 (95% CI, 0.61-0.93) for FRAP, 0.76 (95% CI, 0.61-0.93) for TEAC and 0.71 (95% CI, 0.57-0.89) for TRAP. The inverse association was apparently - though not significantly - stronger for rectal than for colon cancer. This is the first case-control study indicating consistent inverse relations between dietary TAC and colorectal cancer risk. What's new? A diet rich in fruit and vegetables has been associated with a reduced risk of common cancers, including colorectal cancer. Total antioxidant capacity (TAC), rather than individual components, has been suggested as a relevant factor for cancer risk. In this case-control study of over 6,000 patients, the authors used several different techniques to measure the dietary TAC of subjects' usual diet, and found a consistent inverse relationship between dietary TAC and colorectal cancer risk. Copyright © 2013 UICC.

Rossi, M Lugo, A Lagiou, P Zucchetto, A Polesel, J Serraino, D Negri, E Trichopoulos, D La Vecchia, C eng Multicenter Study Research Support, Non-U.S. Gov't England 2011/11/05 06:00 Ann Oncol. 2012 Jun;23(6):1488-93. doi: 10.1093/annonc/mdr475. Epub 2011 Nov 2.; International audience; BACKGROUND: Four cohort studies have examined the relation between flavonoids and pancreatic cancer risk providing inconsistent results. PATIENTS AND METHODS: We conducted a case-control study between 1991 and 2008 in Northern Italy. Subjects were 326 cases with incident pancreatic cancer and 652 frequency-matched controls (admitted to the same hospitals as cases for acute non-neoplastic conditions) who answered a reproducible and valid food-frequency questionnaire. We computed odds ratios (ORs) using logistic regression models conditioned on gender, age and study center, and adjusted for education, history of diabetes, tobacco smoking, alcohol drinking and energy intake. RESULTS: Proanthocyanidins with three or more mers were inversely related to pancreatic cancer risk. The ORs were similar in all classes of polymers with three or more mers and in their combination (OR for the highest versus the lowest quintile of intake, 0.41; 95% confidence interval 0.24-0.69), and did not substantially change after adjustment for fruit and vegetable consumption, and for vitamin C and folate intakes. Eating an additional portion of fruits rich in proanthocyanidins every day reduced the risk of pancreatic cancer by 25%. CONCLUSION: Dietary proanthocyanidins-mostly present in apples, pears and pulses-may convey some protection against pancreatic cancer risk.

Bosetti, C Filomeno, M Riso, P Polesel, J Levi, F Talamini, R Montella, M Negri, E Franceschi, S La Vecchia, C eng Research Support, Non-U.S. Gov't England 2012/02/14 06:00 Ann Oncol. 2012 Aug;23(8):2198-203. doi: 10.1093/annonc/mdr604. Epub 2012 Feb 10.; International audience; BACKGROUND: Cruciferous vegetables have been suggested to protect against various cancers, though the issue is open to discussion. To further understand their role, we analyzed data from a network of case-control studies conducted in Italy and Switzerland. PATIENTS AND METHODS: The studies included a total of 1468 cancers of the oral cavity/pharynx, 505 of the esophagus, 230 of the stomach, 2390 of the colorectum, 185 of the liver, 326 of the pancreas, 852 of the larynx, 3034 of the breast, 367 of the endometrium, 1031 of the ovary, 1294 of the prostate, 767 of the kidney, and 11,492 controls. All cancers were incident, histologically confirmed; controls were subjects admitted to the same network of hospitals as cases for a wide spectrum of acute nonneoplastic conditions. RESULTS: The multivariate odds ratio (OR) for consumption of cruciferous vegetables at least once a week as compared with no/occasional consumption was significantly reduced for cancer of the oral cavity/pharynx (OR=0.83), esophagus (OR=0.72), colorectum (OR=0.83), breast (OR=0.83), and kidney (OR=0.68). The OR was below unity, but not significant, for stomach (OR=0.90), liver (OR=0.72), pancreatic (OR=0.90), laryngeal (OR=0.84), endometrial (OR=0.93), ovarian (OR=0.91), and prostate (OR=0.87) cancer. CONCLUSION: This large series of studies provides additional evidence of a favorable effect of cruciferous vegetables on several common cancers.

Bosetti, Cristina Rosato, Valentina Polesel, Jerry Levi, Fabio Talamini, Renato Montella, Maurizio Negri, Eva Tavani, Alessandra Zucchetto, Antonella Franceschi, Silvia Corrao, Giovanni La Vecchia, Carlo eng Research Support, Non-U.S. Gov't 2012/04/24 06:00 Nutr Cancer. 2012;64(5):643-51. doi: 10.1080/01635581.2012.676141. Epub 2012 Apr 20.; International audience; Diabetes has been associated to the risk of a few cancer sites, though quantification of this association in various populations remains open to discussion. We analyzed the relation between diabetes and the risk of various cancers in an integrated series of case-control studies conducted in Italy and Switzerland between 1991 and 2009. The studies included 1,468 oral and pharyngeal, 505 esophageal, 230 gastric, 2,390 colorectal, 185 liver, 326 pancreatic, 852 laryngeal, 3,034 breast, 607 endometrial, 1,031 ovarian, 1,294 prostate, and 767 renal cell cancer cases and 12,060 hospital controls. The multivariate odds ratios (OR) for subjects with diabetes as compared to those without-adjusted for major identified confounding factors for the cancers considered through logistic regression models-were significantly elevated for cancers of the oral cavity/pharynx (OR = 1.58), esophagus (OR = 2.52), colorectum (OR = 1.23), liver (OR = 3.52), pancreas (OR = 3.32), postmenopausal breast (OR = 1.76), and endometrium (OR = 1.70). For cancers of the oral cavity, esophagus, colorectum, liver, and postmenopausal breast, the excess risk persisted over 10 yr since diagnosis of diabetes. Our data confirm and further quantify the association of diabetes with colorectal, liver, pancreatic, postmenopausal breast, and endometrial cancer and suggest forthe first time that diabetes may also increase the risk of oral/pharyngeal and esophageal cancer.

Turati, Federica Edefonti, Valeria Talamini, Renato Ferraroni, Monica Malvezzi, Matteo Bravi, Francesca Franceschi, Silvia Montella, Maurizio Polesel, Jerry Zucchetto, Antonella La Vecchia, Carlo Negri, Eva Decarli, Adriano eng Comparative Study Meta-Analysis Research Support, Non-U.S. Gov't Baltimore, Md. 2011/11/19 06:00 Hepatology. 2012 May;55(5):1416-25. doi: 10.1002/hep.24794. Epub 2012 Mar 21.; International audience; Familial clustering of hepatocellular carcinoma (HCC) has been frequently reported in eastern Asiatic countries, where hepatitis B infection is common. Little is known about the relationship between family history of liver cancer and HCC in Western populations. We carried out a case-control study in Italy, involving 229 HCC cases and 431 hospital controls. Data on family history were summarized through a binary indicator (yes/no) and a family history score (FHscore), considering selected family characteristics. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were obtained from unconditional multiple logistic regression models, including terms for age, sex, study center, education, tobacco smoking, alcohol drinking, hepatitis B surface antigen, and/or anti-hepatitis C virus positivity. We also performed a meta-analysis on family history of liver cancer and liver cancer updated to April 2011 using random-effects models. After adjustment for chronic infection with hepatitis B/C viruses, family history of liver cancer was associated with HCC risk, when using both the binary indicator (OR, 2.38; 95% CI, 1.01-5.58) and the FHscore, with increasing ORs for successive score categories. Compared to subjects without family history and no chronic infection with hepatitis B/C viruses, the OR for those exposed to both risk factors was 72.48 (95% CI, 21.92-239.73). In the meta-analysis, based on nine case-control and four cohort studies, for a total of approximately 3,600 liver cancer cases, the pooled relative risk for family history of liver cancer was 2.50 (95% CI, 2.06-3.03). CONCLUSION: A family history of liver cancer increases HCC risk, independently of hepatitis. The combination of family history of liver cancer and hepatitis B/C serum markers is associated with an over 70-fold elevated HCC risk.

We assessed the relation between metabolic syndrome (MetS), its components, and pancreatic cancer risk in an Italian case-control study and performed a meta-analysis of epidemiological studies published up to February 2011. The case-control study included 326 patients with incident pancreatic cancer and 652 controls admitted to the same hospitals for acute, non-neoplastic conditions. MetS was defined as having at least 3 conditions among diabetes, drug:treated hypertension, hyperlipidemia, and body mass index at least 25 kg/m(2) at age 30 years. We computed multivariate odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) from logistic regression models adjusted for tobacco smoking, education, and other sociodemographic variables. For the meta-analysis, we calculated summary relative risks (RRs) using random-effects models. The OR of pancreatic cancer in the case-control study was 2.36 (95% CI, 1.43-3.90) for diabetes, 0.77 (95% CI, 0.55-1.08) for hypertension, 1.38 (95% CI, 0.94-2.01) for hypercholesterolemia, and 1.27 (95% CI, 0.91-1.78) for being overweight at age 30 years. The risk was significantly increased for subjects with 3 or more MetS components (OR = 2.13, 95% CI 1.01-4.49) compared with subjects with no component, the estimates being consistent among strata of sex, age, and alcohol consumption. The meta-analysis included 3 cohort studies and our case-control study, and found a summary RR of 1.55 (95% CI, 1.19-2.01) for subjects with MetS. Metabolic syndrome is related to pancreatic cancer risk. Diabetes is the key component related to risk. (C) 2011 Elsevier Inc. All rights reserved.

Nasopharyngeal carcinoma (NPC) is rare in western Countries. Tobacco smoking is a well-recognised risk factor, whereas the role of alcohol drinking is still in debate. We conducted a hospital-based case-control study in Italy on 150, histologically-confirmed, NPC cases of Caucasian ethnicity, aged 18-76 years, including 118 undifferentiated NPCs and 22 differentiated squamous-cell NPC. Controls were 450 Caucasian cancer-free patients admitted to general hospitals for acute conditions. Cases and controls were matched according to sex, age, and place of residence. Logistic regression was used to estimate odds ratios (OR) and the corresponding 95% confidence intervals (CI) while adjusting for known confounders. No significant association emerged between tobacco smoking and all NPCs (OR for current vs. never smokers = 1.52; 95% CI: 0.89-2.60). Conversely, for differentiated NPC only, statistically significant elevated OR were associated with increasing smoking intensity (OR for >= 15 cigarettes/day = 5.40; 95% CI: 1.34-21.76) and duration of the habit (OR for >= 32 years = 4.48; 95% CI: 1.11-18.04). Although alcohol drinking was not, per se, significantly associated to NPC risk, the combination of tobacco smoking and alcohol drinking accounted for 57% of differentiated NPCs, whereas it accounted for only 14% of undifferentiated carcinomas. Our findings suggest that, in western populations, NPC includes two separate entities: the differentiated NPC, associated with tobacco smoking like other cancers of head and neck, and the undifferentiated NPC, upon which tobacco smoking has little or no influence. (C) 2011 Elsevier Ltd. All rights reserved.

Background: Information on the relation between acrylamide exposure and risk of pancreatic cancer is scanty and inconsistent. Patients and methods: We investigated the issue in a case–control study conducted from 1991 to 2008 in Northern Italy. Cases were 326 patients with incident pancreatic cancer, admitted to major teaching and general hospitals. Controls were 652 subjects admitted to the same hospitals with acute non-neoplastic conditions. Acrylamide mean content of various food items was derived from international databases and Italian sources. Odds ratios (ORs) and 95% confidence intervals (CIs) of pancreatic cancer were derived using conditional logistic regression adjusted for several covariates, including energy intake. Results: The ORs of pancreatic cancer for subsequent quintiles of acrylamide intake, as compared with the lowest one, were 1.48 (95% CI 0.88–2.50), 1.57 (95% CI 0.91–2.69), 1.70 (95% CI 0.98–2.96) and 1.49 (95% CI 0.83–2.70), with no trend in risk (P value 0.21). The OR for an increase in acrylamide intake of 10 μg/day was 1.01 (95% CI 0.92–1.10). No meaningful difference between ORs was found in strata of smoking habit, alcohol drinking, body mass index and other selected covariates. Conclusion: This study found no association between dietary acrylamide and pancreatic cancer in an Italian population.

BACKGROUND: Endometrial cancer is strongly associated with body mass index (BMI), but the influence of BMI history and of different types of obesity is uncertain. METHODS: A case-control study was carried out in Italy including 454 cases and 908 controls admitted to hospital for acute non-hormone-related conditions. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using multivariate logistic and spline regression models. RESULTS: The OR for BMI > 30 at diagnosis compared with 20 to

Objective: Several studies have shown an inverse relation between vegetable and fruit intake and pancreatic cancer, but no specific beneficial component of such foods has been consistently identified. We considered the role of 15 selected vitamins and carotenoids and 6 minerals on pancreatic cancer risk in an Italian case–control study. Methods: Subjects were 326 patients with incident pancreatic cancer and 652 controls, admitted to the same hospitals as cases for acute conditions. Micronutrient computation was based on a validated and reproducible food-frequency questionnaire. We estimated the odds ratios (OR) and confidence intervals (CI) using conditional logistic regression models, adjusted for various confounding factors and for energy intake, according to the residual model. Results: Comparing the highest to the lowest quintile of intake, the OR were 0.60 (95% CI 0.36–0.98) for vitamin E, 0.44 (95% CI 0.27–0.73) for vitamin C, 0.56 (95% CI 0.34–0.93) for folate, and 0.57 (95% CI 0.35–0.92) for potassium. No significant inverse associations were observed for α-carotene (OR = 0.69, 95% CI 0.43–1.12), β-carotene (OR = 0.64, 95% CI 0.39–1.06), and β-cryptoxanthin (OR = 0.66, 95% CI 0.39–1.09). No relation was found for other micronutrients considered. Conclusion: Our findings support a favorable role of vitamins E and C, selected carotenoids, and folate on pancreatic carcinogenesis.

Background. The epidemiological evidence on the relation between dietary fiber intake and endometrial cancer is contradictory. Consequently, a case-control study was carried out to further investigate the role of dietary fiber intake in the etiology of endometrial cancer. Material and methods. Cases were 454 women with incident, histologically confirmed, endometrial cancer admitted to major teaching and general hospitals. Controls were 908 women admitted for acute, non-neoplastic conditions to the same hospital network. Information on diet was elicited using a validated food frequency questionnaire. Results. Odds ratios (OR) and 95% confidence intervals (CI) for quintiles of various types of fiber were estimated after allowance for total energy intake and other potential confounding factors. Lignin intake was significantly inversely related to endometrial cancer (OR=0.6 for the highest versus the lowest quintile of intake; 95%CI: 0.4-0.9) with a slightly significant linear trend in risk (p-value=0.04). Discussion. Data suggest the potential importance of lignin in the prevention of endometrial cancer at Italian consumption levels.

Preclinical findings suggest that aspirin might inhibit pancreatic carcinogenesis, but epidemiological data are scanty and controversial. The role of aspirin use in pancreatic cancer is further analyzed in a multicentric hospital-based case-control study conducted in Italy between 1991 and 2008. Cases were 308 patients with incident pancreatic cancer and controls were 477 patients admitted to the same hospitals as cases for acute conditions, not related to risk factors for pancreatic cancer. A total of 22 cases (7%) and 37 controls (8%) reported regular aspirin use, with a corresponding adjusted odds ratio (OR) of 0.87 [95% confidence interval (CI): 0.47-1.61]. A slight protection, although not significant, was observed for duration of use >= 5 years (OR= 0.53; 95% CI: 0.21-1.33) and for time since first use >= 10 years (OR= 0.69; 95% CI: 0.25-1.93). The risk of pancreatic cancer was significantly below unity for current users of >= 5 years (OR= 0.23; 95% CI: 0.06-0.90), but the risk was based on three cases and 16 controls only. We observed no association between regular aspirin use and pancreatic cancer risk, although our results suggested a possible protective effect for long-term current users. European Journal of Cancer Prevention 19: 352-354 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Objective To investigate the association between dietary habits and pancreatic cancer. Methods Between 1991 and 2008, we conducted a hospitalbased case-control study in northern Italy. Cases: 326 patients (median age 63 years) with incident pancreatic cancer admitted to general hospitals in the areas of Milan and Pordenone, northern Italy. Controls: 652 patients (median age 63 years) with acute non-neoplastic conditions admitted to the same hospital network of cases. Diet was assessed using a validated food frequency questionnaire. Conditional logistic regression was used to estimate odds ratios (OR) and the corresponding 95% confidence intervals (CI). Results Frequent meat consumption was associated to a twofold increased risk of pancreatic cancer (95% CI: 1.18-3.36); the risk was significant for meat cooked by boiling/ stewing or broiling/roasting. Added table sugar (OR = 2.23; 95% CI: 1.34-3.71) and potatoes (OR = 1.79; 95% CI: 1.12-2.86) were related to pancreatic cancer. An inverse association emerged for non-citrus fruits (OR = 0.41; 95% CI: 0.24-0.69), cooked vegetables (OR = 0.57; 95% CI: 0.36-0.92), and, possibly, for pulses (OR = 0.59; 95% CI: 0.35-1.00). Conclusions The present study supports an inverse association between fruits and vegetables and pancreatic cancer risk, and it confirms a direct relation with meat. The increased risk for table sugar suggests that insulin resistance may play a role in pancreatic carcinogenesis.

In Italy, pancreatic cancer accounts for approximately 5% of cancer-related deaths. Tobacco smoking is the major established risk factor for this cancer, whereas the role of alcohol consumption is open to debate. Between 1991 and 2008, we conducted a hospital-based case-control study on pancreatic cancer in northern Italy Cases were 326 patients (median age 63 years) with incident pancreatic cancer admitted to major general hospitals. Controls were 652 patients (median age 63 years) with acute non-neoplastic conditions admitted to the same hospital network of cases. Multiple logistic regression was used to estimate the odds ratios (OR) and the corresponding 95% confidence intervals (CI). Pancreatic cancer was associated to current smoking (OR = 1.68; 95% Cl: 1.13-2.48), and the risk rose with increasing number of cigarettes/day (OR = 2.04; 95% CI: 1.14-3.66 for >= 20 cigarettes/day). No association emerged for former smokers (OR = 0.98; 95% CI: 0.66-1.45). Alcohol consumption was associated to increased pancreatic cancer risk, but ORs were significant only among heavy drinkers (ORs: 2.03 and 3.42 for 21-34 and >= 35 drinks/week, respectively). Pancreatic cancer risk was 4.3-fold higher in heavy smokers (>= 20 cigarettes/day) and heavy drinkers (>= 21 drinks/week) in comparison with never smokers who drunk

Background. The epidemiologic evidence on dietary vitamins E and C and prostate cancer is controversial. Therefore, a case-control study was carried out to investigate the role of dietary intake of vitamins E and C in the etiology of prostate cancer. Material and methods. Cases were 1 294 men with incident, histologically confirmed prostate cancer, admitted to the major teaching and general hospitals of five Italian areas between 1991 and 2002. Controls were 1 451 men admitted for acute, non-neoplastic conditions to the same hospitals. Information on dietary habits and nutrient intake was elicited using a validated food frequency questionnaire including 78 food groups and recipes. Odds ratios (OR) and 95% confidence intervals (CI) for increasing levels of vitamin intake were estimated after allowance for total energy intake and other confounding factors. Results. Vitamin E showed a significant inverse association with prostate cancer (OR = 0.78 for the highest versus the lowest tertile of intake, 95% CI: 0.58-0.96; p-value for trend = 0.02), whereas for vitamin C the inverse association was of borderline statistical significance (OR = 0.86; 95% CI: 0.65-1.08). Results were consistent in strata of age, body mass index, and family history of prostate cancer. Discussion. The present study shows an inverse association between dietary intake of vitamins E and prostate cancer incidence. This finding is likely to reflect the influence of diet itself since supplementation or food fortification with vitamins is rare in the Italian population.

The objective of this study was to evaluate the association between cigarette smoking and endometrial cancer risk by investigating potential modifying effects of menopausal status, obesity, and exogenous hormones. We pooled data from three case-control studies with the same study design conducted in Italy and Switzerland between 1982 and 2006. Overall, 1446 incident endometrial cancers and 4076 hospital controls were enrolled. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models, conditioned on study and centre, and adjusted for age, period of interview, age at menarche, parity, and body mass index. In comparison with never smokers, current smokers showed reduced endometrial cancer risk (OR: 0.80; 95% CI: 0.66-0.96), with a 28% decrease in risk for smoking >= 20 cigarettes/day. The association did not vary according to menopausal status, oral contraceptive use, or hormone replacement therapy. However, heterogeneity emerged according to body mass index among postmenopausal women, with obese women showing the greatest risk reduction for current smoking (OR: 0.47; 95% CI: 0.27-0.81). in postmenopausal women, obesity turned out to be an important modifier of the association between cigarette smoking and the risk of endometrial cancer. This finding calls for caution in interpreting the favorable effects of cigarette smoking, considering the toxic and carcinogenic effects of tobacco. European Journal of Cancer Prevention 18:476-481 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.

The role of selected macronutrients, fatty acids and cholesterol in the etiology of renal cell carcinoma (RCC) was analyzed using data from a case-control study conducted in 4 Italian areas between 1992 and 2004. Cases were 767 patients with incident, histologically confirmed RCC, admitted to major teaching and general hospitals of the study areas. Controls were 1,534 subjects admitted for acute, nonneoplastic conditions to the same hospitals. Information on dietary habits and nutrient intake was elicited using a validated food frequency questionnaire including 78 food groups and recipes. Odds ratios (OR) and 95% confidence intervals (CI) for increasing levels of nutrient intake were estimated after allowance for total energy intake and other potential confounding factors. A direct association with RCC was found for starch intake (OR = 1.9 for highest versus lowest quintile of intake; 95% Cl: 1.4-2.6, p-value for trend = 0.001), while an inverse association was found for fats from vegetable sources (OR = 0.6; 95% CI: 0.5-0.8; p-value for trend = 0.002), unsaturated fatty acids (OR = 0.5; 95% Cl: 0.4-0.7; p-value for trend = 0.0002), and polyunsaturated fatty acids (OR = 0.5; 95% Cl: 0.40.7; p-value for trend = 0.001). Among polyunsaturated fatty acids, linoleic acid (OR = 0.5; 95% CI: 0.4-0.7; p-value for trend = 0.0001) and linolenic acid (OR = 0.7; 95% CI: 0.5-1.0; p-value for trend = 0.01) were inversely related to RCC. When 6 major macronutrients were included in the same model, the adverse effect of high intake of starch remained statistically significant, together with the protective effect of polyunsaturated fatty acids. Results were consistent in strata of age, body mass index, treated hypertension, energy intake, stage and family history of RCC. (C) 2008 Wiley-Liss, Inc.

A role of hormone-related factors in renal cell cancer (RCC) etiology has been hypothesized, but the epidemiological evidence is inconsistent. The present study aimed at evaluating the effect of reproductive, menstrual and other gender-specific variables on RCC risk among women. This study is part of a larger hospital-based, case-control study on RCC risk, conducted in northern, central and southern Italy. Cases were 273 women, below age 80, with histologically confirmed, incident RCC. Controls were 546 women hospitalized for acute, nonneoplastic conditions, frequency-matched to cases by age and center. Odds ratios (OR) and 95% confidence intervals (CI) were computed using multiple logistic regression models. RCC risk was inversely related to age at first birth (OR = 0.7, 95% CI 0.5-1.0, for >= 25 years vs.