Cancer Trends and Risk Factors in Cyprus

Cyprus, a European Union member state, is a small island in the Mediterranean with a population approaching 900,000 people. Cancer is the second leading cause of death; more therapeutic options for any patient with the disease are available in a central oncology centre in the capital of the island (Nicosia) and fewer therapeutic options (e.g. chemotherapy and hormone therapy only) in a few other public hospitals. Palliative care is offered in several hospices and hospitals, although the field needs improvement. With regards to screening, a national breast cancer screening programme has been in place countrywide since 2007 and is offered free of charge to women between the ages of 50 and 69 years, while colorectal and prostate cancer screening is performed on an individual basis (a pilot programme for colorectal cancer screening was recently initiated). Genetic testing is available for breast and colon cancer. To improve understanding of the causes of cancer in the country, a cancer research centre was established in 2010 (Mediterranean Centre for Cancer Research). Recent epidemiologic work has revealed increasing cancer trends in Cyprus; prostate cancer is the most common in men and breast cancer is the most common in women. Interestingly, thyroid cancer incidence in women has been rising from 1998 to 2008. Cancer of the colon and rectum is also on the rise affecting both sexes. Overall, cancer incidence in Cyprus is lower than other EuroMed countries with similar lifestyle and geography

Differential Methylation Patterns in Lean and Obese Non-Alcoholic Steatohepatitis-Associated Hepatocellular Carcinoma

BACKGROUND: Nonalcoholic fatty liver disease affects about 24% of the world\u27s population and may progress to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC). While more common in those that are obese, NASH-HCC can develop in lean individuals. The mechanisms by which HCC develops and the role of epigenetic changes in the context of obesity and normal weight are not well understood. METHODS: In this study, we used previously generated mouse models of lean and obese HCC using a choline deficient/high trans-fat/fructose/cholesterol diet and a choline supplemented/high trans-fat/fructose/cholesterol diet, respectively, to evaluate methylation differences in HCC progression in lean versus obese mice. Differentially methylated regions were determined using reduced representation bisulfite sequencing. RESULTS: A larger number of differentially methylated regions (DMRs) were seen in NASH-HCC progression in the obese mice compared to the non-obese mice. No overlap existed in the DMRs with the largest methylation differences between the two models. In lean NASH-HCC, methylation differences were seen in genes involved with cancer progression and prognosis (including HCC), such as CHCHD2, FSCN1, and ZDHHC12, and lipid metabolism, including PNPLA6 and LDLRAP1. In obese NASH- HCC, methylation differences were seen in genes known to be associated with HCC, including RNF217, GJA8, PTPRE, PSAPL1, and LRRC8D. Genes involved in Wnt-signaling pathways were enriched in hypomethylated DMRs in the obese NASH-HCC. CONCLUSIONS: These data suggest that differential methylation may play a role in hepatocarcinogenesis in lean versus obese NASH. Hypomethylation of Wnt signaling pathway-related genes in obese mice may drive progression of HCC, while progression of HCC in lean mice may be driven through other signaling pathways, including lipid metabolism

Reduction of Polyunsaturated Fatty Acids with Tumor Progression in a Lean Non-Alcoholic Steatohepatitis-Associated Hepatocellular Carcinoma Mouse Model

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. While obesity and diabetes are the hallmarks of NAFLD, it also develops in lean individuals in the absence of metabolic syndrome, with a prevalence of 7 percent in the U.S. and 25-30 percent in some Asian countries. NAFLD represents the spectrum of liver disease, starting with excess liver fat accumulation (NAFL) that can progress to nonalcoholic steatohepatitis (NASH), cirrhosis and ultimately hepatocellular carcinoma (HCC). To date, the pathogenesis of lean NASH-HCC is poorly understood and a mouse model is lacking. We aimed to develop a mouse model of lean NASH-HCC using a choline deficient and high trans-fat/sucrose/cholesterol diet to enable better understanding of its molecular pathogenesis. Methods: C57BL/6N mice were fed this diet starting at 4 weeks of age for 52 weeks and were compared to mice fed an isocaloric low fat control diet for the same duration. C57BL/6N mice were chosen instead of the C57BL/6J mice due to the high susceptibility of C57BL/6J mice to diet-induced obesity. The plasma and tumor fatty acid profile of these mice was also investigated. Results: Nearly 61% of the mice developed lean NASH-HCC. These mice showed reduction of plasma polyunsaturated fatty acids (PUFAs) (linolenic acids (α and γ, ω-3 and ω-6, respectively), eicosapentanoic acid (ω-3), docosahexanoic acid (ω-3), and linoleic acid (ω-6)) and increasing levels over time in mice with pre-malignant lesions. Conclusions: We developed a novel high penetrance diet-induced lean NASH-HCC mouse model. Plasma PUFA levels were reduced with tumor progression in parallel with reduced expression of genes controlling desaturase expression suggesting their potential use as biomarkers for lean NASH-HCC progression as well as chemopreventive molecules

Thirty-Day Unplanned Readmission and Its Effect on 90-Day Mortality in Hepatocellular Carcinoma Patients Undergoing Partial Hepatectomy

Background: Despite advances of surgical techniques, hepatectomy continues to be potentially dangerous and is associated with postoperative mortality, morbidity and readmission. The objective of this study was to determine the effect of 30-day unplanned readmission on ‘conditional’ 90-day mortality among hepatocellular carcinoma (HCC) patients who underwent partial hepatectomy. Methods: National Cancer Database (NCDB) was queried from 2004 to 2012 for patients with hepatocellular carcinoma (HCC) who underwent partial hepatectomy. Thirty-day unplanned readmission rate, and associated risk factors, was determined for 7,696 patients. The association between 30-day unplanned readmission and conditional 90-day mortality was further addressed. Results: The 30-day unplanned readmission rate for patients with HCC who underwent partial hepatectomy was 5.2%. Risk factors associated with 30-day unplanned readmission were sex, race/ethnicity, Charlson-Deyo score, and annual hospital hepatectomy volume. An overall adjusted odds of having conditional 90-day mortality was 2.325 times higher (95% CI 1.643 - 3.219) among patients with a history of 30-day unplanned readmission than those without. This association was dependent on age, sex, race/ethnicity, insurance status, alpha-fetoprotein (AFP), liver fibrosis, Charlson-Deyo comorbidity score and annual hospital hepatectomy volume. Conclusion: Efforts in patient care should be taken to reduce 30-day unplanned readmission after partial hepatectomy for patients with HCC to reduce conditional 90-day mortality

Geographic Trends of Tobacco-Related Cancers in Cyprus

BACKGROUND: Causal relationships have been previously established between smoking and various cancers. In Cyprus, 39 % of men and 14 % of women reported daily smoking in 2008. The objective of this study was to compare the incidence of tobacco-related cancers to all other cancers by district and rural-urban classification to understand the impact of tobacco in Cyprus. METHODS: Data on lung, urinary bladder, oral, pharyngeal, head/neck, and laryngeal cancers were obtained from the Cyprus Cancer Registry (1998-2008). There were 3,635 patients with tobacco-related cancers and 18,780 with non-tobacco cancers. Univariate analysis comparing tobacco-related cancers and all other cancers were conducted with regards to age at diagnosis, age groups, sex, smoking status, disease stage, and rural/urban status, with a p-value of 0.05 considered significant. Smoking prevalence, lung cancer, and bladder cancer rates of Cyprus were also compared to a number of other European countries. RESULTS: Patients with tobacco-related cancers were older than those with non-tobacco cancers (mean age 67.2 ± 12.4 vs. 62.4 ± 17.1, p \u3c 0.0001). Among those with tobacco-related cancers, 80.1 % were male compared to 45.4 % males with other cancer types. The proportion of ever smokers was higher among males compared to females in urban and rural districts. Sub-districts 41 (Age Adjusted Rate (AAR) 41.9, 95 % CI: 35.7-48.1), 60 (AAR 40.3, 95 % CI: 35.2-45.3), and 50 (AAR 36.3, 95 % CI: 33.8-38.7) had the highest rates of tobacco-related cancers. The overall tobacco-related cancer rate was the highest among males in urban districts (AAR 60.8, 95 % CI: 58.2-63.5). Among tobacco-related cancers, lung cancer had the highest overall AAR (17.9 per 100,000) while head and neck cancer had the lowest overall AAR (5.3 per 100,000). Additionally, even though Cypriot males aged 65-69 years old exhibited higher smoking prevalence than other European countries, the overall lung and bladder cancer rates were lower in Cyprus. CONCLUSION: Despite the high proportion of smokers in Cyprus, cancer rates are low compared to other countries. Future in-depth measurements of relevant risk factors and smoking exposure can help understand this phenomenon and provide insights for cancer prevention

Knowledge and Attitudes of Cypriots on Melanoma Prevention: Is there a Public Health Concern?

BACKGROUND: Melanoma is the deadliest type of skin cancer. It is the eighth most common cancer in males and the tenth in females in Cyprus, an island in the Mediterranean with a high ultraviolet (UV) index. Cyprus is expected to be strongly affected by climate change and consequently, melanoma will likely become an increasing public health problem. Melanoma prevention is possible; however, it is unknown if people living in Cyprus are aware of melanoma and prevention methods. To this end, we used a validated survey to evaluate the level of melanoma knowledge and factors associated with it in the Cypriot population. METHODS: We conducted a 47-item survey with sections on demographics, knowledge of melanoma and risk factors, attitudes toward relevant health practices, and protective behaviors among six hundred Cypriot residents from October 2015 to April 2016. RESULTS: Our results revealed that only 59% of participants check their skin for moles, 87% protect their skin from the sun during summer holidays, and 57% do not take measures to protect their skin from the sun during non-holiday periods. Protective behavior was positively associated with educational level (P=0.016) and district of residence (P CONCLUSIONS: There are gaps in melanoma knowledge and prevention practices in the study population. Further education on melanoma and its prevention should be specifically targeted to individuals of lower education levels as well as teenagers, such that protective behaviors for melanoma are adopted early in life

Barriers of Colorectal Cancer Screening in Rural USA: A Systematic Review

INTRODUCTION: Colorectal cancer (CRC) screening rates are lower in rural areas in the USA. To guide the design of interventions to improve CRC screening, a systematic review was conducted to identify CRC screening barriers for rural populations. METHODS: A search was conducted in four literature databases - Medline, CINAHL, Embase, and Scopus - for articles from 1998 to 2017 that examine CRC screening barriers in rural areas. This review included a total of 27 articles reporting perceived CRC screening barriers by rural residents or providers or examining factors associated with CRC screening of rural populations in the USA. RESULTS: The most frequently reported barriers were high screening cost and lack of insurance coverage, embarrassment or discomfort undergoing screening, lack of knowledge or perceived need on CRC screening, and lack of physician recommendation. These barriers were confirmed in quantitative studies examining their association with CRC screening status. Age, marital status, and race/ethnicity were the most frequently reported factors associated with CRC screening in rural areas. Lack of prevention attitude toward cancer, perceived lack of privacy, shortage of specialists, and distance to test facilities were reported as rural-specific barriers for CRC screening. CONCLUSIONS: Main barriers for CRC screening at both the individual and healthcare system level are identified in rural areas and they are in line with those found in urban areas in general. In particular, lack of prevention attitude toward cancer, perceived lack of privacy, shortage of specialists, and distance to test facilities disproportionately hamper CRC screening for rural Americans

Development and Validation of a Questionnaire to Assess Awareness and Knowledge of Nonalcoholic Fatty Liver Disease, a Liver Cancer Etiological Factor, among Chinese Young Adults

PURPOSE: Despite the increasing prevalence of nonalcoholic fatty liver disease (NAFLD), a liver cancer etiological factor, among Chinese young adults (CYA), there is a lack of valid, reliable, ready-to-use survey instruments for assessing awareness and knowledge of NAFLD in this population. The aims of this study were to develop, validate, and assess the reliability of a web-based, self-administered questionnaire evaluating awareness and knowledge of NAFLD among CYA. METHODS: Based on review of relevant literature, a draft questionnaire was initially developed. Face and content validity of the questionnaire was evaluated by an expert panel of seven gastroenterologists. The construct validity was tested through item analysis based on item response theory. Reliability assessment included test-retest for stability and test for internal consistency. Two pilot tests were conducted among 60 randomly selected students at Lanzhou University, China, through WeChat App. RESULTS: The content validity and clarity indexes were both greater than 0.85. Face validity was established by concluding that questions had no issue with feasibility, readability, clarity of wording, clarity of layout, and style. Response rates for two pilot tests were 96.7% (58 out of 60) and 98.3% (59 out of 60), respectively. Results testing the construct validity showed estimated amount of information obtained by the test between -3 and +3 range of ability was 97.57%. The test-retest reliability (Pearson\u27s r) was 0.62. The internal consistency (KR20) was 0.92. CONCLUSIONS: This newly developed questionnaire is a reliable and valid instrument for assessing awareness and knowledge of NAFLD among this sample from CYA

Exposure to Toxicants Associated With Use and Transitions Between Cigarettes, e-Cigarettes, and No Tobacco

Importance: Transitions between e-cigarettes and cigarettes are common among tobacco users, but empirical evidence on the health outcomes of switching tobacco products is scarce. Objectives: To examine changes in urinary biomarkers between baseline and 1-year follow-up among adult tobacco users switching between e-cigarettes and cigarettes. Design, Setting, and Participants: This cohort study used data from wave 1 (baseline, September 2013 to December 2014) and wave 2 (1-year follow-up, October 2014 to October 2015) of the Population Assessment of Tobacco and Health Study. A subset of the probability sample of US adults who voluntarily provided biospecimens at 2 waves was analyzed. Participants were divided into 3 mutually exclusive groups at baseline: exclusive cigarette smokers, exclusive e-cigarette users, and dual users. Data analysis was performed in 2021. Exposures: Harmful and potentially harmful constituents included nicotine metabolites, tobacco-specific nitrosamines (TSNAs; including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL]), metals, polycyclic aromatic hydrocarbons (PAHs), and volatile organic compounds (VOCs). Main Outcomes and Measures: Within-participant changes in 55 urinary biomarkers of exposure (BOEs) to harmful and potentially harmful constituents were examined using multivariable regression models. Results: Among 3211 participants (55.6% women, 68.3% White, 13.2% Black, and 11.8% Hispanic) at baseline, 21.9% of exclusive cigarette users, 42.8% of exclusive e-cigarette users, and 62.1% of dual users changed product use at follow-up (all percentages are weighted). There was a significant reduction in urine concentrations of TSNAs, PAHs, and VOCs when users transitioned from exclusive cigarette to exclusive e-cigarette use, with a 92% decrease in NNAL, from a mean of 168.4 pg/mg creatinine (95% CI, 102.3-277.1 pg/mg creatinine) to 12.9 pg/mg creatinine (95% CI, 6.4-25.7 pg/mg creatinine; P \u3c .001). A similar panel of BOEs decreased when dual users transitioned to exclusive e-cigarette use; NNAL levels decreased by 96%, from a mean of 143.4 pg/mg creatinine (95% CI, 86.7-237.0 pg/mg creatinine) to 6.3 pg/mg creatinine (95% CI, 3.5-11.4 pg/mg creatinine; P \u3c .001). Nicotine metabolites, TSNAs, PAHs, and VOCs significantly increased when baseline exclusive e-cigarette users transitioned to exclusive cigarette use or dual use. Switching from exclusive cigarette use to dual use was not associated with significant decreases in BOEs. Conclusions and Relevance: This national cohort study provides evidence on the potential harm reduction associated with transitioning from exclusive cigarette use or dual use to exclusive e-cigarette use. e-Cigarettes tend to supplement cigarettes through dual use instead of cessation at the population level. Continuous monitoring of BOE at the population level and assessment of BOE change by product transition are warranted, as well as defined adverse health outcomes

Vaccination Coverage and Awareness of Hepatitis B Virus Among Healthcare Students at a University in Cyprus

Introduction: The risk for healthcare students to get infected by transmitting infectious viruses, including hepatitis B virus (HBV), in a hospital setting is extremely high through exposure to blood and/or body secretions. Aim: The aim of this work was to evaluate both the vaccination history of healthcare students at a University in Cyprus and their serologic immunity against HBV. In addition, we assessed their knowledge and behaviors towards the transmission and prevention of hepatitis B (HB). Results: Total amount of 168 students participated in this study and more than 50% of them provided complete documentation of vaccination history against HBV. Antibodies levels ×10 mIU/mL to HB surface antigen (HBsAg) were detected for the 98.8% of healthcare students while 1.2% of the participants tested positive for HBsAg and antibodies to HB core antigen indicating chronic infection. Our study also revealed significant gaps in the knowledge of healthcare students on the efficiency of the vaccine against HBV and in terms of the HBV transmission. Conclusions: More information needs to be provided to healthcare students in Cyprus regarding HBV transmission and vaccination. In addition, there is a need for intervention to provide a safer workplace environment