Prostate cancer (PCa) is a prevalent malignancy affecting men worldwide, and plant-based diets have been widely advocated for their health benefits. The aim of this study was to test the association between general, healthy, and unhealthy pro-vegetarian plant-based diets and PCa severity on 118 consecutive patients undergoing prostatectomy in a university hospital in Italy. Food frequency questionnaires were used to calculate scores for dietary patterns. Multivariate logistic regression analyses were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to test the associations. A general plant-based diet was not associated with cancer severity, while patients reporting a higher adherence to a healthy plant-based diet were less likely to have a more severe PCa (for medium/high vs. low-risk PCa, OR = 0.27, 95% CI: 0.08, 0.88; for high vs. medium/low-risk PCa, OR = 0.09, 95% CI: 0.02, 0.39). Patients resulting in higher adherence to an unhealthy plant-based diet were more likely to be diagnosed with more severe PCa (OR = 6.15, 95% CI: 1.70, 22.24). In conclusion, plant-based dietary patterns may have a different impact on PCa severity depending on the quality of the foods included.

Background and purpose: Lung cancer is the leading cause of death in both men and women, constituting a major public health problem worldwide. Non-small-cell lung cancer accounts for 85%–90% of all lung cancers. We propose a compound that successfully fights tumor growth in vivo by targeting the enzyme GARS1.Experimental approach: We present an in-depth investigation of the mechanism through which Fraisinib [meso-(p-acetamidophenyl)-calix(4)pyrrole] affects the human lung adenocarcinoma A549 cell line. In a xenografted model of non-small-cell lung cancer, Fraisinib was found to reduce tumor mass volume without affecting the vital parameters or body weight of mice. Through a computational approach, we uncovered that glycyl-tRNA synthetase is its molecular target. Differential proteomics analysis further confirmed that pathways regulated by Fraisinib are consistent with glycyl-tRNA synthetase inhibition.Key results: Fraisinib displays a strong anti-tumoral potential coupled with limited toxicity in mice. Glycyl-tRNA synthetase has been identified and validated as a protein target of this compound. By inhibiting GARS1, Fraisinib modulates different key biological processes involved in tumoral growth, aggressiveness, and invasiveness.Conclusion and implications: The overall results indicate that Fraisinib is a powerful inhibitor of non-small-cell lung cancer growth by exerting its action on the enzyme GARS1 while displaying marginal toxicity in animal models. Together with the proven ability of this compound to cross the blood–brain barrier, we can assess that Fraisinib can kill two birds with one stone: targeting the primary tumor and its metastases “in one shot.” Taken together, we suggest that inhibiting GARS1 expression and/or GARS1 enzymatic activity may be innovative molecular targets for cancer treatment.

BACKGROUND: Prostate cancer (PCa) is a significant health concern, and its incidence and prevalence are influenced by various lifestyle factors, including diet. In recent years, the Mediterranean diet has gained popularity due to its potential health benefits and associations with reduced risk for various diseases. However, the impact of the Mediterranean diet on PCa remains a topic of debate. OBJECTIVE: The aim of this study was to test the association between adherence to the Mediterranean diet and PCa severity. METHODS: Background, clinical and dietary information (from food frequency questionnaires) were collected from 118 consecutive patients attending a university hospital in Southern Italy. Multivariate logistic regression analyses were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to test the associations. RESULTS: Patients reporting higher adherence to the Mediterranean diet were less likely to have more at risk PCa both when comparing intermediate/high vs. low risk and high vs. intermediate /low risk PCa (OR = 0.12, 95% CI: 0.02, 0.85 and OR = 0.05, 95% CI: 0.01, 0.31, respectively). CONCLUSIONS: In conclusion, higher adherence to the Mediterranean diet may be associated with a clinically less severe clinical PCa.

Background: The level of food processing has gained interest as a potential determinant of human health. The aim of this study was to assess the relationship between the level of food processing and prostate cancer severity. Methods: A sample of 120 consecutive patients were examined for the following: their dietary habits, assessed through validated food frequency questionnaires; their dietary intake of food groups, categorized according to the NOVA classification; and their severity of prostate cancer, categorized into risk groups according to European Association of Urology (EAU) guidelines. Uni- and multivariate logistic regression analyses were performed to test the association between the variables of interest. Results: Individuals reporting a higher consumption of unprocessed/minimally processed foods were less likely to have greater prostate cancer severity than those who consumed less of them in the energy-adjusted model (odds ratio (OR) = 0.38, 95% confidence interval (CI): 1.17–0.84, p = 0.017 and OR = 0.33, 95% CI: 0.12–0.91, p = 0.032 for medium/high vs. low grade and high vs. medium/low grade prostate cancers, respectively); however, after adjusting for potential confounding factors, the association was not significant anymore. A borderline association was also found between a higher consumption of ultra-processed foods and greater prostate cancer severity in the energy-adjusted model (OR = 2.11, 95% CI: 0.998–4.44; p = 0.051), but again the association was not significant anymore after adjusting for the other covariates. Conclusions: The level of food processing seems not to be independently associated with prostate cancer severity, while potentially related to other factors that need further investigation.

Background: Migrants are a vulnerable and neglected population. We aimed at investigating cancer proportionate rates in migrants in Sicily, Southern Italy. Methods: We extracted data on new cancer cases diagnosed between 2004 and 2019 from the Eastern Sicily cancer registry. We compared the adjusted proportionate morbidity ratio (PMR) for the most common cancer types among migrants and non-migrants. We fitted multivariate logistic regression models comparing one cancer to all other cancers to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for migration status. The analysis was stratified by region of origin. Results: Overall, 4726 new cancer cases occurred in migrants between 2004 and 2019, 63.5% of those among women and 224,211 in non-migrants, including 54.5% among men, with odds for migrants/non-migrants of 2.1%. Migrants had an increased proportion of cervical (PMR = 2.68, 95% CI = 2.29–3.10) and lung cancer (PMR = 1.20, 95% CI = 1.07–1.33). The highest OR in migrants was observed for cervical cancer (OR = 3.54, 95% CI = 2.99–4.20). Colorectal cancer was decreased among migrants (OR = 0.86, 95% CI = 0.77–0.96). Conclusions: Migrants to Sicily have higher odds of cervical cancer and a decreased risk of colorectal cancer compared to non-migrants. Increased odds were also detected for lung cancer, in particular in women. Different cancer patterns could be observed based on the region of origin. HPV-related cancers need targeted attention in migrants living in Sicily.

Background: Cancer survivors are at risk of developing second primary cancers (SPC). We investigated the risk of SPC in colorectal cancer (CRC) survivors in Sicily, Southern Italy. Methods: We analyzed data from the Eastern Sicily cancer registry covering 2.5 million people diagnosed and followed up between 2003 and 2017. We calculated the standardized incidence ratio (SIR) and 95% confidence interval (CI) of SPC overall and by cancer type, using the general Sicily population rates as reference. Results: A total of 19,040 cases of CRC and 1453 cases of SPC were included in the analysis. Mean age of occurrence of SPC was 68.1. The SIR for any SPC was 1.11 (95% CI 1.05–1.17); it was higher in women (1.18; 95% CI 1.08–1.29) than in men (1.07; 95% CI 0.97–1.14, p-value of difference 0.07). The SIR was increased for SPC from the ovary (SIR 2.01; 95% CI 1.33–2.95), kidney (SIR 2.00; 95% CI 1.54–2.56), endometrium (SIR 1.94; 95% CI 1.45–2.54), bladder (SIR 1.22, 95% CI 1.04–1.43) and stomach (1.29; 95% CI 0.98–1.66). The SIR for CRC as SPC was 0.84 (95% CI 0.70–1.01). No increased incidence was found for lung, prostate, breast, thyroid and liver cancer. The SIR for SPC overall and several cancers decreased with time of follow-up. Conclusions: In this population, CRC survivors have an 11% higher risk of developing a SPC than the general population, particularly cancers of the ovary, kidney, endometrium, bladder and stomach. Follow-up for SPC is required, especially during the first 5 years from CRC diagnosis.

Fish represents one of the most important dietary sources of omega-3 polyunsaturated fatty acids, which are known to be associated with various health benefits. This study aimed to systematically review existing meta-analyses of observational studies exploring the association between fish intake and various health outcomes. A systematic search of electronic databases was conducted to retrieve a total of 63 studies. Evidence was deemed as possible for the association between higher fish intake and decreased risk of the acute coronary syndrome, liver cancer, and depression, and limited for other outcomes (including age-related macular degeneration, Alzheimer's disease, heart failure, all-cause and coronary heart disease mortality, total and ischaemic stroke) due to heterogeneity between results and potential otherwise inexplicable confounding factors. In conclusion, results from epidemiological studies support the mechanistic effects associated with omega-3 fatty acids from high fish consumption, but evidence needs to be further corroborated with more reliable results.

Background: Cancer tissue is characterized by low oxygen availability triggering neo angiogenesis and metastatisation. Accordingly, oxidation is a possible strategy for counteracting cancer progression and relapses. Previous studies used ozone gas, administered by invasive methods, both in experimental animals and clinical studies, transiently decreasing cancer growth. This study evaluated the effect of ozonized oils (administered either topically or orally) on cancer, exploring triggered molecular mechanisms. Methods: In vitro, in lung and glioblastoma cancer cells, ozonized oils having a high ozonide content suppressed cancer cell viability by triggering mitochondrial damage, intracellular calcium release, and apoptosis. In vivo, a total of 115 cancer patients (age 58 ± 14 years; 44 males, 71 females) were treated with ozonized oil as complementary therapy in addition to standard chemo/radio therapeutic regimens for up to 4 years. Results: Cancer diagnoses were brain glioblastoma, pancreas adenocarcinoma, skin epithelioma, lung cancer (small and non-small cell lung cancer), colon adenocarcinoma, breast cancer, prostate adenocarcinoma. Survival rate was significantly improved in cancer patients receiving HOO as integrative therapy as compared with those receiving standard treatment only. Conclusions: These results indicate that ozonized oils at high ozonide may represent an innovation in complementary cancer therapy worthy of further clinical studies.

Meat consumption has represented an important evolutionary step for humans. However, modern patterns of consumption, including excess intake, type of meat and cooking method have been the focus of attention as a potential cause of rise in non-communicable diseases. The aim of this study was to investigate the association between total, red and processed meat with health outcomes and to assess the level of evidence by performing a systematic search of meta-analyses of prospective cohort studies. Convincing evidence of the association between increased risk of (i) colorectal adenoma, lung cancer, CHD and stroke, (ii) colorectal adenoma, ovarian, prostate, renal and stomach cancers, CHD and stroke and (iii) colon and bladder cancer was found for excess intake of total, red and processed meat, respectively. Possible negative associations with other health outcomes have been reported. Excess meat consumption may be detrimental to health, with a major impact on cardiometabolic and cancer risk.

MicroRNA and DNA adduct biomarkers may be used to identify the contribution of environmental pollution to some types of cancers. The aim of this study was to use integrated DNA adducts and microRNAs analyses to study retrospectively the contribution of exposures to environmental carcinogens to lung cancer in 64 non-smokers living in Sicily and Catania city near to the Etna volcano. MicroRNAs were extracted from cancer lung biopsies, and from the surrounding lung normal tissue. The expression of 2549 human microRNAs was analyzed by microarray. Benzo(a)Pyrene-DNA adducts levels were analyzed in the patients’ blood by HPLC−fluorescence detection. Correlations between tetrols and environmental exposures were calculated using Pearson coefficients and regression variable plots. Compared with the healthy tissue, 273 microRNAs were downregulated in lung cancer. Tetrols levels were inversely related both with the distance from Etna and years since smoking cessation, but they were not significantly correlated to environmental exposures. The analysis of the microRNA environmental signatures indicates the contribution of environmental factors to the analyzed lung cancers in the following decreasing rank: (a) car traffic, (b) passive smoke, (c) radon, and (d) volcano ashes. These results provide evidence that microRNA analysis can be used to retrospectively investigate the contribution of environmental factors in human lung cancer occurring in non-smokers.

Oncogene mutations may be drivers of the carcinogenesis process. MicroRNA (miRNA) alterations may be adaptive or pathogenic and can have consequences only when mutation in the controlled oncogenes occurs. The aim of this research was to analyze the interplay between miRNA expression and oncogene mutation. A total of 2549 miRNAs were analyzed in cancer tissue—in surrounding normal lung tissue collected from 64 non-smoking patients and in blood plasma. Mutations in 92 hotspots of 22 oncogenes were tested in the lung cancer tissue. MicroRNA alterations were related to the mutations occurring in cancer patients. Conversely, the frequency of mutation occurrence was variable and spanned from the k-ras and p53 mutation detected in 30% of patients to 20% of patients in which no mutation was detected. The prediction of survival at a 3-year follow up did not occur for mutation analysis but was, conversely, well evident for miRNA analysis highlighting a pattern of miRNA distinguishing between survivors and death in patients 3 years before this clinical onset. A signature of six lung cancer specific miRNAs occurring both in the lungs and blood was identified. The obtained results provide evidence that the analysis of both miRNA and oncogene mutations was more informative than the oncogene mutation analysis currently performed in clinical practice.

Background: Meningiomas are the most common primary brain tumors, followed by glioblastomas. Nevertheless, no previous studies have been conducted to evaluate the epidemiology of meningiomas and glioblastomas in the southern region of Italy. Thus, the aim of our study was to evaluate incidence, temporal trend and survival rate of meningiomas and glioblastomas in the province of Catania during the study period. Moreover, a geoepidemiological analysis was performed in order to identify possible geographical and temporal clusters. Methods: All subjects with meningiomas and glioblastomas diagnosed from 2003 to 2016 in the province of Catania were collected, using the local cancer registry. Incidence rate (IR) was calculated by gender, age-groups and tumor behavior. Temporal changes in incidence trend were assessed using a Joinpoint regression analysis while survival analysis was performed using Kaplan-Meier method. Cluster analysis was performed using Kulldorff's spatial scan statistic. Results: In the province of Catania, a total of 1488 cases of meningiomas and 443 cases of glioblastomas were identified from 2003 to 2016, with an IR of 9.8/100,000 person-years (95%CI 9.3-10.3) and 2.9/100,000 person-years (95%CI 2.7-3.2), respectively. Meningiomas were more common among women (p-value<0.0001), while glioblastomas among men (p-value<0.0001). IR progressively increased over the ages, reaching a peak in the 75-84 and 65-74 years-old group in, respectively, meningiomas and glioblastomas. Mean survival was higher in subjects diagnosed with meningiomas as compared to those with glioblastomas (10.7 years and 15.8 months, respectively), with age as the strongest risk factor for death. Spatial and space-time cluster of high incidence of meningiomas was detected in a small community on the eastern flank of the Mt. Etna volcano. Conclusions: Epidemiology of meningioma and glioblastoma in the province of Catania is close to that reported worldwide. Spatial and space-time cluster of meningiomas were found in Pedara. Further studies on risks factor are necessary.

Background: Exposure to metals/metalloids, including essential and nonessential elements, has been associated to male reproductive health in animals. However, findings from human studies are inconsistent. Objectives: To investigate the impact of exposure to multiple metals/metalloids at environmental levels on the conventional human semen-quality parameters. Materials and methods: Men living in rural or industrial areas were recruited by personalized letters. No exclusion criteria were applied. Each man provided one semen sample and one blood sample. We analyzed the semen sample both to determine conventional sperm parameters (concentration, progressive motility and normal forms) and to quantify lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), nickel (Ni), vanadium (V) and selenium (Se) levels. The levels of these metals/metalloids were also quantified in venous blood and spermatozoa samples. Associations between the blood/seminal plasma metal/metalloid levels and semen quality parameters were assessed using confounder adjusted logistic regression models. Correlation and interactions between blood/seminal plasma and semen metal/metalloid levels were investigated using the Spearman's correlation. Results: We found a positive association of seminal plasma cadmium level with lower Total count (OR = 4.48, 95%CI 0.25-80); whereas lead (OR = 4.51, 95%CI 0.86-23) and cadmium (OR = 3.45, 95%CI 0.77-16) seminal plasma levels had a positive association with progressive sperm motility. Overall, these associations remained suggestive after adjustment, though statistically unstable risks. Finally, we found weak interactions between beneficial effects of Se and detrimental ones only for Cd and Pb blood level on sperm concentration, total sperm count and progressive sperm motility. Conclusions: Our findings suggest that environmental exposure to Pb and Cd contributes to a decline in human semen quality, whereas Se can have beneficial effects. Measurements of metals/metalloids in the seminal fluid may be more predictable of semen quality than conventional blood measurements

Introduction: Primary brain tumors (PBTs) account for approximately 2% of all cancers and are associated with significant morbidity and mortality. However, only few epidemiological studies focus on PBTs in Italy. The aim of this study was to evaluate incidence, temporal trend, and survival rate of all PBTs in the province of Catania during the study period. Methods: All patients diagnosed with PBTs in the province of Catania during the 2003-2016 were identified through the local cancer registry. All cases were classified by histology according to 2007 WHO classification of central nervous system tumors, using the International Classification of Diseases for Oncology, 3rd edition codes. The incidence rate (IR) was calculated for all PBTs and by gender, histology, age-groups, and behavior. Trend analysis was performed using a piecewise log-linear model. Results: A total of 3,819 cases were identified with a female/male ratio of 1.45. The IR for all PBTs was 25.3/100,000 person-years (95% confidence interval 24.5–26.1). Most PBTs were nonmalignant (59.5%, IR = 15.0) with a female predominance. Conversely, malignant tumors (32.4%, IR = 8.2) were more common among men, with a female/male ratio of 0.9. The most frequently reported histology was meningioma (39.0%, IR = 9.8), followed by glioblastoma (11.6%, IR = 2.9). A peak of incidence was found in the 75–84 years age-group, with an IR of 77.6/100,000 person-years. Overall, no increase in incidence was observed along the study period. Conclusions: The IR of PBTs in the province of Catania is close to incidence reported worldwide. Further studies on risk factors are necessary.

The Erice 56 Charter titled ?Impact of the environment on the health: from theory to practice? was unanimously approved at the end of the 56th course of the ?International School of Epidemiology and Preventive Medicine G. D?Alessandro? held from 3rd to November 7, 2019 in Erice ? Sicily (Italy) and promoted by the Study Group of ?Environment and Health? of the Italian Society of Hygiene, Preventive Medicine and Public Health. The course, that included lectures, open discussions and guided working groups, was aimed to provide a general training on epidemiological and toxicological aspects of the environmental health impact, to be used by public health professionals for risk assessment, without forgetting the risk communications. At the end of the course 12 key points were agreed among teachers and students: they underlined the need of specific training and research, in the perspective of ?One Health? and ?Global Health?, also facing emerging scientific and methodological issues and focusing on communication towards stakeholders. This Discussion highlight the need to improve knowledge of Health and Environment topic in all sectors of health and environmental prevention and management.

Consumption of nuts and legumes has been associated with several health benefits. The aim of this study was to systematically review existing meta-analyses of observational studies on nut and legume intake and non-communicable diseases, and assess the level of evidence. Out of the six meta-analyses focussed on legume and 15 on nut intake, a possible association with decreased risk of colorectal adenoma and coronary heart disease was found for higher legume consumption, and a decreased risk of cardiovascular and cancer mortality, colon cancer, hypertension and ischaemic stroke for higher nut consumption. The association between legume consumption and cardiovascular diseases (CVDs), as well as nut consumption and risk of cancer, CVD incidence and all-cause mortality, was deemed as "limited" due to heterogeneity between results and/or potential confounding factors. General benefit towards better health can be observed for nut and legume consumption. Further studies are needed to better elucidate potential confounding factors.

Abstract Whole grains have been associated with a number of health benefits. We systematically reviewed existing meta-analyses of observational studies and evaluated the level of evidence for their putative effects based on pre-selected criteria. Of the 23 included studies, we found convincing evidence of an inverse association between whole grain consumption and risk of type-2 diabetes and colorectal cancer; possible evidence of decreased risk of colon cancer and cardiovascular mortality with increased whole grain intake, as well as increased risk of prostate cancer. Limited or insufficient evidence was available for all other outcomes investigated. Overall findings are encouraging for a positive effect of whole grain consumption on certain diseases, especially highly prevalent metabolic diseases, however, uncertainty of some negative associations deserves further attention. Abstract 44 Whole grains have been associated with a number of health benefits. We systematically reviewed 45 existing meta-analyses of observational studies and evaluated the level of evidence for their putative 46 effects based on pre-selected criteria. Of the 23 included studies, we found convincing evidence of 47 an inverse association between whole grain consumption and risk of type-2 diabetes and colorectal 48 cancer; possible evidence of decreased risk of colon cancer and cardiovascular mortality with 49 increased whole grain intake, as well as increased risk of prostate cancer. Limited or insufficient 50 evidence was available for all other outcomes investigated. Overall findings are encouraging for a 51 positive effect of whole grain consumption on certain diseases, especially highly prevalent 52 metabolic diseases, however, uncertainty of some negative associations deserves further attention. 53

Objective The impact of a screening programme on colorectal cancer (CRC) incidence in its target population depends on several variables, including coverage with invitations, participation rate, positivity rate of the screening test, compliance with an invitation to second-level assessment and endoscopists' sensitivity. We propose a synthetic indicator that may account for all the variables influencing the potential impact of a screening programme on CRC incidence. Design We defined the 'rate of advanced adenoma on the target population' (AA-TAP) as the rate of patients who received a diagnosis of advanced adenoma within a screening programme, divided by the programme target population. We computed the AA-TAP for the CRC Italian screening programmes (biennial faecal immunochemical test, target population 50-69 year olds) using the data of the Italian National Survey from 2003 to 2016, overall and by region, and assessed the association between AA-TAP and CRC incidence fitting a linear regression between the trend of regional CRC incidence rates in 50-74 year old subjects and the cumulative AA-TAP. Results In 2016, the AA-TAP at a national level was 105x100 000, whereas significant differences were observed between the northern and central regions (respectively 126 and 149x100 000) and the South and Islands (36x100 000). The cumulative AA-TAP from 2004 to 2012 was significantly correlated with the difference between CRC incidence rates in 2013-2014 and those in 2003-2004 (p=0.009). Conclusion The AA-TAP summarises into a single indicator the potential impact of a screening programme in reducing CRC incidence rates.

Evidence on consumption of dairy foods and human health is contradictory. This study aimed to summarize the level of evidence of dairy consumption on various health outcomes. A systematic search for meta-analyses was performed: study design, dose-response relationship, heterogeneity and agreement of results over time, and identification of potential confounding factors were considered to assess the level of evidence. Convincing and probable evidence of decreased risk of colorectal cancer, hypertension and cardiovascular disease, elevated blood pressure and fatal stroke, respectively, was found for total dairy consumption; possible decreased risk of breast cancer, metabolic syndrome, stroke and type-2 diabetes, and increased risk of prostate cancer and Parkinson's disease was also found. Similar, yet not entirely consistent evidence for individual dairy products was reported. Among potential confounding factors, geographical localisation and fat content of dairy have been detected. In conclusions, dairy may be part of a healthy diet; however, additional studies exploring confounding factors are needed to ascertain the potential detrimental effects.