Reducing relapse through maintenance steroid treatment can decrease the cancer risk in patients with IgG4-sclerosing cholangitis: Based on a Japanese nationwide study.

OBJECTIVE: IgG4-related sclerosing cholangitis (IgG4-SC) is recognized as a benign steroid-responsive disease; however, little is known about the risk of development of cancer in patients with IgG4-SC and about how to counter this risk. DESIGN: We conducted a retrospective review of the data of 924 patients with IgG4-SC selected from a Japanese nationwide survey. The incidence, type of malignancy, and risk of malignancy in these patients were examined. Then, the standardized incidence ratio (SIR) of cancer in patients with IgG4-SC was calculated. RESULTS: Relapse was recognized in 19.7% (182/924) of patients, and cancer development was noted in 15% (139/924) of patients. Multivariate analysis identified only relapse as an independent risk factor for the development of cancer. In most of these patients with pancreato-biliary cancer, the cancer developed within 8 years after the diagnosis of IgG4-SC. The SIR for cancer after the diagnosis of IgG4-SC was 12.68 (95% confidence interval [CI] 6.89-8.79). The SIRs of cancers involving the biliary system and pancreas were 27.35 and 18.43, respectively. The cumulative survival rate was significantly better in the group that received maintenance steroid treatment (MST) than in the group that did not; thus, MST influenced the prognosis of these patients. CONCLUSION: Among the cancers, the risk of pancreatic and biliary cancers is the highest in these patients. Because of the elevated cancer risk, surveillance after the diagnosis and management to prevent relapse are important in patients with IgG4-SC to reduce the risk of development of cancer.

Investigating Causal Associations of Diet-Derived Circulating Antioxidants with the Risk of Digestive System Cancers: A Mendelian Randomization Study.

Molecular mechanisms and observational studies have found that diet-derived antioxidants are associated with digestive system cancers, whereas there is a lack of causal evidence from randomized clinical trials. In this study, we aimed to assess the causality of these associations through a Mendelian randomization (MR) study. Single nucleotide polymorphisms of diet-derived circulating antioxidants (i.e., α- and γ-tocopherol, ascorbate, retinol, ß-carotene, lycopene, and urate), accessed by absolute levels and relative metabolite concentrations, were used as genetic instruments. Summary statistics for digestive system cancers were obtained from the UK Biobank and FinnGen studies. Two-sample MR analyses were performed in each of the two outcome databases, followed by a meta-analysis. The inverse-variance weighted MR was adopted as the primary analysis. Five additional MR methods (likelihood-based MR, MR-Egger, weighted median, penalized weighted median, and MR-PRESSO) and replicate MR analyses for outcomes from different sources were used as sensitivity analyses. Genetically determined antioxidants were not significantly associated with five digestive system cancers, after correcting for multiple tests. However, we found suggestive evidence that absolute ascorbate levels were negatively associated with colon cancer in UK Biobank-the odds ratio (OR) per unit increase in ascorbate was 0.774 (95% confidence interval [CI] 0.608-0.985, p = 0.037), which was consistent with the results in FinnGen, and the combined OR was 0.764 (95% CI 0.623-0.936, p = 0.010). Likewise, higher absolute retinol levels suggestively reduced the pancreatic cancer risk in FinnGen-the OR per 10% unit increase in ln-transformed retinol was 0.705 (95% CI 0.529-0.940, p = 0.017), which was consistent with the results in UK Biobank and the combined OR was 0.747 (95% CI, 0.584-0.955, p = 0.020). Sensitivity analyses verified the above suggestive evidence. Our findings suggest that higher levels of antioxidants are unlikely to be a causal protective factor for most digestive system cancers, except for the suggestive protective effects of ascorbate on colon cancer and of retinol on pancreatic cancer.

Association between physical activity and digestive-system cancer: An updated systematic review and meta-analysis.

BACKGROUND: Physical activity (PA) may have an impact on digestive-system cancer (DSC) by improving insulin sensitivity and anticancer immune function and by reducing the exposure of the digestive tract to carcinogens by stimulating gastrointestinal motility, thus reducing transit time. The current study aimed to determine the effect of PA on different types of DSC via a systematic review and meta-analysis. METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched for relevant studies in PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure. Using a random effects model, the relationship between PA and different types of DSC was analyzed. RESULTS: The data used for meta-analysis were derived from 161 risk estimates in 47 studies involving 5,797,768 participants and 55,162 cases. We assessed the pooled associations between high vs. low PA levels and the risk of DSC (risk ratio (RR)  = 0.82, 95% confidence interval (95%CI): 0.79-0.85), colon cancer (RR = 0.81, 95%CI: 0.76-0.87), rectal cancer (RR = 0.88, 95%CI: 0.80-0.98), colorectal cancer (RR = 0.77, 95%CI: 0.69-0.85), gallbladder cancer (RR = 0.79, 95%CI: 0.64-0.98), gastric cancer (RR = 0.83, 95%CI: 0.76-0.91), liver cancer (RR = 0.73, 0.60-0.89), oropharyngeal cancer (RR = 0.79, 95%CI: 0.72-0.87), and pancreatic cancer (RR = 0.85, 95%CI: 0.78-0.93). The findings were comparable between case-control studies (RR = 0.73, 95%CI: 0.68-0.78) and prospective cohort studies (RR = 0.88, 95%CI: 0.80-0.91). The meta-analysis of 9 studies reporting low, moderate, and high PA levels, with 17 risk estimates, showed that compared to low PA, moderate PA may also reduce the risk of DSC (RR = 0.89, 95%CI: 0.80-1.00), while compared to moderate PA, high PA seemed to slightly increase the risk of DSC, although the results were not statistically significant (RR = 1.11, 95%CI: 0.94-1.32). In addition, limited evidence from 5 studies suggested that meeting the international PA guidelines might not significantly reduce the risk of DSC (RR = 0.96, 95%CI: 0.91-1.02). CONCLUSION: Compared to previous research, this systematic review has provided more comprehensive information about the inverse relationship between PA and DSC risk. The updated evidence from the current meta-analysis indicates that a moderate-to-high PA level is a common protective factor that can significantly lower the overall risk of DSC. However, the reduction rate for specific cancers may vary. In addition, limited evidence suggests that meeting the international PA guidelines might not significantly reduce the risk of DSC. Thus, future studies must be conducted to determine the optimal dosage, frequency, intensity, and duration of PA required to reduce DSC risk effectively.

Omega-3 PUFA intake and the risk of digestive system cancers: A meta-analysis of observational studies.

BACKGROUND: A growing number of epidemiological studies have suggested a possible association between long-chain omega-3 polyunsaturated fatty acid (PUFA) intake and the risk of cancers, but the results have been inconsistent. We aimed to conduct a meta-analysis to assess the association of omega-3 PUFA consumption with digestive system cancers. METHODS: Relevant observational studies were identified through a comprehensive search of PubMed, Embase, and the Web of Science through December 2019 and by reviewing the references of the retrieved articles. The relative risks (RRs) of digestive system cancers associated with omega-3 PUFA intake were estimated using a random-effect model and were stratified by region, sex, study design, type of omega-3 PUFAs, smoking status, alcohol consumption, BMI, and physical activity. RESULTS: Twenty-five studies (8 case-control studies and 17 cohort studies) involving 1,247,271 participants and 23,173 patients with digestive system cancers were included in this analysis. The risk of digestive system cancers decreased by 17% in individuals who consumed omega-3 PUFAs (RR = 0.83, 95% confidence interval (CI), 0.76-0.91). The risk estimates of digestive system cancers varied by cancer sites, study location, study design, type of omega-3 PUFAs, and other confounders (smoking, alcohol consumption, body mass index, and physical activity). Visual inspection of funnel plots and the Begg's and Egger's tests revealed no evidence of publication bias. CONCLUSION: The findings show that omega-3 PUFAs should be as a healthy dietary component for the prevention of digestive system cancers. Cancer incidence decreases with increasing omega-3 PUFAs intake for most digestive system cancer sites. The relation between omega-3 PUFAs and digestive system cancers RR is similar among different populations.

Geographical and Temporal Variation in the Incidence and Mortality of Hepato-Pancreato-Biliary Primary Malignancies:1990-2017.

BACKGROUND: Hepatic, pancreas, and biliary (HPB) cancers pose serious challenges to global health care systems. These malignancies demonstrate great geographical variations with shifting trends over time. The aim of the present study was to determine the recent trends in incidence, prevalence, and mortality of primary HPB malignancies to guide the further development of effective strategies for prevention, screening, and treatment. METHODS: The Global Burden of Disease (GBD) dataset 1990-2017 was interrogated for end point variables by age, sex, year, and geography. Epidemiologic data were modeled in DisMod-MR 2.1, a Bayesian meta-regression tool that pools data points from different sources and adjusts for known sources of variability. Global Burden of Disease data were extracted from 284 country-year, and 976 subnational-year combinations from 27 countries in North America, Latin America, Europe, India, and New Zealand. RESULTS: Although the global incidence of primary HPB malignancies increased by 1.43% from 1990 to 2017 (1,400,739 cases), the incidence of extrahepatic biliary and gallbladder malignancies decreased by -0.32% (210,878 cases) over the same period. There was significant variability in the incidence, prevalence, and mortality of HPB cancers by the sociodemographic index (SDI), as well as by geography. The largest incidence increase of primary liver and pancreas cancers was seen in the high-income Asia-Pacific group, followed by the high-income North America and Western Europe groups. The highest incidences and prevalence of extrahepatic biliary and gallbladder malignancies were observed in Asia-Pacific, Southern Latin American, and Andean Latin American regions. In general, mortality rates of HPB malignancies were larger in the low SDI when compared with the high SDI group in all geographical regions. CONCLUSIONS: The global incidence and prevalence of primary liver and pancreatic malignancies continue to increase with great geographical variation. The mortality trends mirror those of the incidence. Although the global incidence and prevalence of extrahepatic biliary and gallbladder malignancies has decreased, the mortality rate has not significantly changed. The results of this article can assist local and regional authorities in policy development to improve health care access for screening, early detection, and treatment of HPB malignancies.

[Influence of food or food groups intake on the occurrence and/or protection of different types of cancer: systematic review]. / Influencia de la ingesta de alimentos o grupos de alimentos en la aparición y/o protección de los diversos tipos de cáncer: revisión sistemática.

INTRODUCTION: Introduction: the diet plays an important role in the origin and prevention of multiple chronic degenerative diseases, such as cardiovascular diseases or cancer. Objective: the main objective of this paper is to analyze the studies that are focused on researching the relationship between the consumption of the particular groups of foods and its importance on the increase and for prevention of the risk of cancer appearance. Methods: a bibliographical review was carried out in the main international databases (PubMed, Scopus and Nutrition Reference). The results were structured in two main sections: those related with the increase of cancer risk and food related with the increase of cancer risk. In the present review, 104 scientific articles have been evaluated. Results: the results have shown a positive association between red meat and colon cancer, alcoholic drinks and liver cancer, and salt and gastric cancer. The Mediterranean diet was associated in a preventive way with digestive and respiratory tract cancer. Conversely, no statistically significant association was found between dairy products and ovarian cancer, carbohydrates and sugars and pancreatic cancer, and tae and breast cancer. Conclusions: as a result, healthy eating guidelines, such as the Mediterranean diet, based on lower consumption of red meat, alcoholic drinks and salt, might contribute to reducing the incidence of colon cancer, liver cancer and gastric cancer.

INTRODUCCIÓN: Introducción: la dieta tiene un importante papel en la formación y en la prevención de múltiples enfermedades crónicas-degenerativas, como son las enfermedades cardiovasculares o el cáncer. Objetivos: el objetivo principal consiste en analizar los estudios que centren su investigación en conocer la relación entre el consumo de determinados grupos de alimentos y su función en el aumento y/o prevención del riesgo de aparición de diversos tipos de cáncer. Métodos: se realizó una revisión sistemática en bases de datos internacionales (PubMed, Scopus y Nutrition Reference). Los estudios fueron estructurados en dos bloques principales: relacionados con el aumento del riesgo de cáncer y alimentos relacionados con el aumento del riesgo de cáncer. Los estudios evaluados en la presente revisión han sido un total de 104 artículos científicos. Resultados: los resultados han mostrado una asociación positiva entre la carne roja y el cáncer de colon, las bebidas alcohólicas y el cáncer de hígado y la sal y el cáncer gástrico. La dieta mediterránea se asoció de manera preventiva con el cáncer del tracto digestivo y respiratorio, mientras que, por otro lado, no se ha encontrado asociación estadísticamente significativa entre el consumo de lácteos y el cáncer de ovario, los carbohidratos o azúcares y el cáncer de páncreas y el té y el cáncer de mama. Conclusiones: por todo ello, patrones de alimentación saludable como la dieta mediterránea, basados en una menor ingesta de carne roja, bebidas alcohólicas y sal, contribuyen a una reducción en la incidencia del cáncer de colon, cáncer de hígado y cáncer de estómago.

Cancer risk, screening and surveillance in primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a rare chronic inflammatory condition mainly of the large bile ducts, affecting predominantly young men, and is associated with the presence of inflammatory bowel disease. There is no known cure for PSC, which progresses to cirrhosis or death over 10-20 years. Hepatobiliary malignancy, especially cholangiocarcinoma, is a feared complication associated with poor overall survival. Screening and surveillance appear to improve overall outcomes. To capture as many relevant studies, broad search criteria were employed within the PubMed database. Given the high prevalence of IBD and its own associations with the development of malignancy two separate search strategies were employed. Results were filtered by English language. The first search identified the risks, epidemiological factors and surveillance strategies for patients with PSC at risk for developing malignancy. MeSH terms included: cholangitis, sclerosing, digestive system neoplasms, liver neoplasms, biliary tract neoplasms, cholangiocarcinoma, gallbladder neoplasms, colonic neoplasms, rectal neoplasms, or pancreatic neoplasms, risk factors, risk, surveillance, epidemiology and screen. The second included inflammatory bowel diseases, Crohn's, or colitis, and assessed for additional malignancies such as lymphoma and skin neoplasms. A total of 288 results returned with 21 duplicates; 267 remaining abstracts were assessed for relevance for inclusion by the authors. Patients with PSC show significantly higher than average risk for the development of hepatobiliary and colonic malignancies including cholangiocarcinoma, gallbladder carcinoma and colorectal carcinoma. Yearly ultrasound surveillance followed with more definitive cross-sectional imaging is prudent to arrive in a timely diagnosis of carcinoma, reducing morbidity and mortality.

Menopausal hormone therapy and cancer risk: An overestimated risk?

AIM: We aimed to assess the overall cancer risk among contemporary menopausal hormone therapy (MHT) users in Sweden and the risk for different cancer types. METHODS: A nationwide Swedish population-based cohort study including all 290,186 women aged ≥ 40 years having used systemic MHT during the study period (July 2005 and December 2012), compared with the Swedish female background population. MHT ever-use (all MHT, oestrogen-only MHT [E-MHT] and oestrogen plus progestin MHT [EP-MHT]) was based on the nationwide Prescribed Drug Registry. Cancer diagnoses were grouped into 16 different anatomical locations, for which standardised incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated. RESULTS: The SIR of any cancer was 1.09 (95% CI: 1.07-1.11) following ever MHT, 1.04 (95% CI: 1.01-1.06) for E-MHT and 1.14 (95% CI: 1.12-1.17) for EP-MHT. The highest SIR was found for EP-MHT among users aged ≥70 years (SIR = 1.33, 95% CI: 1.26-1.40). The risk for invasive breast, endometrial or ovarian cancer combined was increased for any MHT (SIR = 1.31, 95% CI: 1.28-1.34). The risk of invasive breast cancer was increased following MHT and increased with age for EP-MHT users. The risk of gastrointestinal cancers combined was decreased (SIR = 0.90, 95% CI: 0.86-0.94), particularly the oesophagus (SIR = 0.81, 95% CI: 0.64-1.00), liver (SIR = 0.81, 95% CI: 0.65-0.99) and colon (SIR = 0.90, 95% CI: 0.84-0.95). CONCLUSIONS: MHT, notably EP-MHT, was associated with a limited increase in overall cancer risk. The increased risk of female reproductive organ cancers was almost balanced by a decreased risk of gastrointestinal cancers.

[Microbiota and Cancer: a "pas de deux"?] / Gastrointestinale Mikrobiota und Tumorerkrankungen ­ ein "pas de deux"?

Malignant diseases pose an enormous challenge to today's health care system. Advanced pathophysiological understanding of gastrointestinal microbiota and a viable, causal relation to the development of malignant tumors is increasingly becoming the focus of medical research. The following article presents key pathomechanisms of reciprocal interaction between microbiota and malignancy and illustrates the associated role of diet.

Italian cancer figures--Report 2015: The burden of rare cancers in Italy.

OBJECTIVES: This collaborative study, based on data collected by the network of Italian Cancer Registries (AIRTUM), describes the burden of rare cancers in Italy. Estimated number of new rare cancer cases yearly diagnosed (incidence), proportion of patients alive after diagnosis (survival), and estimated number of people still alive after a new cancer diagnosis (prevalence) are provided for about 200 different cancer entities. MATERIALS AND METHODS: Data herein presented were provided by AIRTUM population- based cancer registries (CRs), covering nowadays 52% of the Italian population. This monograph uses the AIRTUM database (January 2015), which includes all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to the International Classification of Diseases for Oncology (ICD-O-3). Data underwent standard quality checks (described in the AIRTUM data management protocol) and were checked against rare-cancer specific quality indicators proposed and published by RARECARE and HAEMACARE (www.rarecarenet.eu; www.haemacare.eu). The definition and list of rare cancers proposed by the RARECAREnet "Information Network on Rare Cancers" project were adopted: rare cancers are entities (defined as a combination of topographical and morphological codes of the ICD-O-3) having an incidence rate of less than 6 per 100,000 per year in the European population. This monograph presents 198 rare cancers grouped in 14 major groups. Crude incidence rates were estimated as the number of all new cancers occurring in 2000-2010 divided by the overall population at risk, for males and females (also for gender-specific tumours).The proportion of rare cancers out of the total cancers (rare and common) by site was also calculated. Incidence rates by sex and age are reported. The expected number of new cases in 2015 in Italy was estimated assuming the incidence in Italy to be the same as in the AIRTUM area. One- and 5-year relative survival estimates of cases aged 0-99 years diagnosed between 2000 and 2008 in the AIRTUM database, and followed up to 31 December 2009, were calculated using complete cohort survival analysis. To estimate the observed prevalence in Italy, incidence and follow-up data from 11 CRs for the period 1992-2006 were used, with a prevalence index date of 1 January 2007. Observed prevalence in the general population was disentangled by time prior to the reference date (≤2 years, 2-5 years, ≤15 years). To calculate the complete prevalence proportion at 1 January 2007 in Italy, the 15-year observed prevalence was corrected by the completeness index, in order to account for those cancer survivors diagnosed before the cancer registry activity started. The completeness index by cancer and age was obtained by means of statistical regression models, using incidence and survival data available in the European RARECAREnet data. RESULTS: In total, 339,403 tumours were included in the incidence analysis. The annual incidence rate (IR) of all 198 rare cancers in the period 2000-2010 was 147 per 100,000 per year, corresponding to about 89,000 new diagnoses in Italy each year, accounting for 25% of all cancer. Five cancers, rare at European level, were not rare in Italy because their IR was higher than 6 per 100,000; these tumours were: diffuse large B-cell lymphoma and squamous cell carcinoma of larynx (whose IRs in Italy were 7 per 100,000), multiple myeloma (IR: 8 per 100,000), hepatocellular carcinoma (IR: 9 per 100,000) and carcinoma of thyroid gland (IR: 14 per 100,000). Among the remaining 193 rare cancers, more than two thirds (No. 139) had an annual IR <0.5 per 100,000, accounting for about 7,100 new cancers cases; for 25 cancer types, the IR ranged between 0.5 and 1 per 100,000, accounting for about 10,000 new diagnoses; while for 29 cancer types the IR was between 1 and 6 per 100,000, accounting for about 41,000 new cancer cases. Among all rare cancers diagnosed in Italy, 7% were rare haematological diseases (IR: 41 per 100,000), 18% were solid rare cancers. Among the latter, the rare epithelial tumours of the digestive system were the most common (23%, IR: 26 per 100,000), followed by epithelial tumours of head and neck (17%, IR: 19) and rare cancers of the female genital system (17%, IR: 17), endocrine tumours (13% including thyroid carcinomas and less than 1% with an IR of 0.4 excluding thyroid carcinomas), sarcomas (8%, IR: 9 per 100,000), central nervous system tumours and rare epithelial tumours of the thoracic cavity (5%with an IR equal to 6 and 5 per 100,000, respectively). The remaining (rare male genital tumours, IR: 4 per 100,000; tumours of eye, IR: 0.7 per 100,000; neuroendocrine tumours, IR: 4 per 100,000; embryonal tumours, IR: 0.4 per 100,000; rare skin tumours and malignant melanoma of mucosae, IR: 0.8 per 100,000) each constituted <4% of all solid rare cancers. Patients with rare cancers were on average younger than those with common cancers. Essentially, all childhood cancers were rare, while after age 40 years, the common cancers (breast, prostate, colon, rectum, and lung) became increasingly more frequent. For 254,821 rare cancers diagnosed in 2000-2008, 5-year RS was on average 55%, lower than the corresponding figures for patients with common cancers (68%). RS was lower for rare cancers than for common cancers at 1 year and continued to diverge up to 3 years, while the gap remained constant from 3 to 5 years after diagnosis. For rare and common cancers, survival decreased with increasing age. Five-year RS was similar and high for both rare and common cancers up to 54 years; it decreased with age, especially after 54 years, with the elderly (75+ years) having a 37% and 20% lower survival than those aged 55-64 years for rare and common cancers, respectively. We estimated that about 900,000 people were alive in Italy with a previous diagnosis of a rare cancer in 2010 (prevalence). The highest prevalence was observed for rare haematological diseases (278 per 100,000) and rare tumours of the female genital system (265 per 100,000). Very low prevalence (<10 prt 100,000) was observed for rare epithelial skin cancers, for rare epithelial tumours of the digestive system and rare epithelial tumours of the thoracic cavity. COMMENTS: One in four cancers cases diagnosed in Italy is a rare cancer, in agreement with estimates of 24% calculated in Europe overall. In Italy, the group of all rare cancers combined, include 5 cancer types with an IR>6 per 100,000 in Italy, in particular thyroid cancer (IR: 14 per 100,000).The exclusion of thyroid carcinoma from rare cancers reduces the proportion of them in Italy in 2010 to 22%. Differences in incidence across population can be due to the different distribution of risk factors (whether environmental, lifestyle, occupational, or genetic), heterogeneous diagnostic intensity activity, as well as different diagnostic capacity; moreover heterogeneity in accuracy of registration may determine some minor differences in the account of rare cancers. Rare cancers had worse prognosis than common cancers at 1, 3, and 5 years from diagnosis. Differences between rare and common cancers were small 1 year after diagnosis, but survival for rare cancers declined more markedly thereafter, consistent with the idea that treatments for rare cancers are less effective than those for common cancers. However, differences in stage at diagnosis could not be excluded, as 1- and 3-year RS for rare cancers was lower than the corresponding figures for common cancers. Moreover, rare cancers include many cancer entities with a bad prognosis (5-year RS <50%): cancer of head and neck, oesophagus, small intestine, ovary, brain, biliary tract, liver, pleura, multiple myeloma, acute myeloid and lymphatic leukaemia; in contrast, most common cancer cases are breast, prostate, and colorectal cancers, which have a good prognosis. The high prevalence observed for rare haematological diseases and rare tumours of the female genital system is due to their high incidence (the majority of haematological diseases are rare and gynaecological cancers added up to fairly high incidence rates) and relatively good prognosis. The low prevalence of rare epithelial tumours of the digestive system was due to the low survival rates of the majority of tumours included in this group (oesophagus, stomach, small intestine, pancreas, and liver), regardless of the high incidence rate of rare epithelial cancers of these sites. This AIRTUM study confirms that rare cancers are a major public health problem in Italy and provides quantitative estimations, for the first time in Italy, to a problem long known to exist. This monograph provides detailed epidemiologic indicators for almost 200 rare cancers, the majority of which (72%) are very rare (IR<0.5 per 100,000). These data are of major interest for different stakeholders. Health care planners can find useful information herein to properly plan and think of how to reorganise health care services. Researchers now have numbers to design clinical trials considering alternative study designs and statistical approaches. Population-based cancer registries with good quality data are the best source of information to describe the rare cancer burden in a population.

The role of chronic inflammation in the development of gastrointestinal cancers: reviewing cancer prevention with natural anti-inflammatory intervention.

Inflammatory mediators alter the local environment of tumors, known as the tumor microenvironment. Mechanistically, chronic inflammation induces DNA damage, but understanding this hazard may help in the search for new chemopreventive agents for gastrointestinal (GI) cancer which attenuate inflammation. In the clinic, GI cancer still remains a major cause of cancer-associated mortality, chemoprevention with anti-inflammatory agents is thought to be a realistic approach to reduce GI cancer. Proton pump inhibitors, monoclonal antibodies targeting tumor necrosis factor-alpha, anti-sense targeted smad7 and non-steroidal anti-inflammatory agents have been investigated for their potential to prevent inflammation-based GI cancer. Besides these, a wide variety of natural products have also shown potential for the prevention of GI cancer. In this review, the authors will provide insights to explain the mechanistic connection between inflammation and GI cancer, as well as describe a feasible cancer prevention strategy based on anti-inflammatory treatments.

Diabetes mellitus and cancer of the digestive organs: An Italian population-based cohort study.

AIMS: The association between diabetes mellitus and the occurrence of digestive organs cancers was investigated in the Italian region Friuli Venezia Giulia. The risk of cancer associated with oral antidiabetic drugs among subjects with type 2 diabetes was also assessed. METHODS: This was a retrospective population-based cohort study based on the 2002-2014 regional administrative health data. Incident digestive cancers were identified through the hospital discharge diagnoses. The incidence rates of cancer at different sites were calculated for type 1 and 2 diabetics and for non-diabetics. Proportional hazard models were built to assess the risk of cancer associated with diabetes and antidiabetic drugs. RESULTS: Diabetes was associated with increased risk of digestive cancers. Liver and pancreatic cancers were associated with the highest hazard ratios. Among type 2 diabetics, total number of metformin prescriptions was associated with reduced risk of most types of digestive cancers; sulfonylureas with reduced risk of stomach and pancreatic cancer. CONCLUSIONS: In this Italian population the excess risk of digestive cancers for diabetic patients was confirmed. Further research is needed to clarify the role of antidiabetic drugs.

Fruit and vegetables and cancer risk: a review of southern European studies.

High intakes of fruit and vegetables may reduce the risk of cancer at several sites. Evidence has been derived mainly from case-control studies. We reviewed the relationship between consumption of vegetables and fruit and the risk of several common cancers in a network of Italian and Swiss case-control studies including over 10,000 cases of fourteen different cancers and about 17,000 controls. Data were suggestive of a protective role of vegetable intake on the risk of several common epithelial cancers. OR for the highest compared with the lowest levels of consumption ranged from 0.2 (larynx, oral cavity and pharynx) to 0.9 (prostate). Inverse associations were found for both raw and cooked vegetables, although for upper digestive tract cancers the former were somewhat stronger. Similar inverse associations were found for cruciferous vegetables. Frequent consumption of allium vegetables was also associated with reduced risk of several cancers. Fruit was a favourable correlate of the risk of several cancers, particularly of the upper digestive tract, with associations generally weaker than those reported for vegetables. A reduced risk of cancers of the digestive tract and larynx was found for high consumption of citrus fruit. Suggestive protections against several forms of cancer, mainly digestive tract cancers, were found for high consumption of apples and tomatoes. High intakes of fibres, flavonoids and proanthocyanidins were inversely related to various forms of cancer. In conclusion, data from our series of case-control studies suggested a favourable role of high intakes of fruit and vegetables in the risk of many common cancers, particularly of the digestive tract. This adds evidence to the indication that aspects of the Mediterranean diet may have a favourable impact not only on CVD, but also on several common (epithelial) cancers, particularly of the digestive tract.

Effects of dietary components on cancer of the digestive system.

Cancer is the second leading cause of death in developed countries and poor diet and physical inactivity are major risk factors in cancer-related deaths. Therefore, interventions to reduce levels of smoking, improve diet, and increase physical activity must become much higher priorities in the general population's health and health care systems. The consumption of fruit and vegetables exerts a preventive effect towards cancer and in recent years natural dietary agents have attracted great attention in the scientific community and among the general public. Foods, such as tomatoes, olive oil, broccoli, garlic, onions, berries, soy bean, honey, tea, aloe vera, grapes, rosemary, basil, chili peppers, carrots, pomegranate, and curcuma contain active components that can influence the initiation and the progression of carcinogenesis, acting on pathways implied in cell proliferation, apoptosis and metastasis. The present review illustrates the main foods and their active components, including their antioxidant, cytotoxic, and pro-apoptotic properties, with a particular focus on the evidence related to cancers of the digestive system.

[Statins and gastrointestinal cancers]. / Statinok és az emésztorendszeri daganatok.

The antitumour effect of statins has already been proven in animal experiments and human cancer cell lines in several gastrointestinal cancers. The chemopreventive mechanism is not completely clarified but the enhancement of oxidative stress, increased autophagy, altered expression of pro- and antiproliferative proteins and their influence on intracellular signaling pathways may play a role. Randomized studies, however, failed to confirme the expected results obtained from experimental studies. The goal of this review is to summarize the data available in the literature regarding the chemopreventive effects of statins on several gastrointestinal cancers. Results of clinical trials suggest that 10-20 mg statin daily has no or minimal antitumour effect. Chemopreventive effect of hydrophilic statins could not be detected but it seems to be significant in the case of hydrophobic statins. There are only few data available on the long-term daily use of 30-40 mg statins. Further long-term evaluation of the effect of statins regarding gastrointestinal cancers is needed, and an analysis of compound- and dose-related subgroups would be beneficial. Chemoprevention with statins cannot yet be accepted as standard medical practice. Use of statins as chemopreventive agents cannot be a substitute for regular oncological screening or surveillance.

[Prevention of malignant neoplasm of digestive organs].

Along with the growth of the overall disease incidence, the cancer incidence is constantly growing as well. Malignancies are diseases that lead to high mortality. This work covers one of the most important provisions of internal diseases--gastroenterology. It is known that the main work of healthcare professionals, therapists, is the diagnosis and treatment, and the second part of their work is prevention (primary, secondary and tertiary) of diseases and on this basis--prevention of malignant diseases. The search of precancerous diseases is always complicated, so it is advisable to create risk groups, which are observed in the dynamics. The Article helps to make the program not only of rational control, but also to designate a circle of the activities continuously replacing oncologic transformation of the observed pathology. The psychological condition of the patient in terms of impact of oncological process is included into the examination, as well as the role of health care professionals--therapist, oncologist and psychologist on the stabilization of the process of recovery and cancer patients.

The role of thyroid hormone signaling in the prevention of digestive system cancers.

Thyroid hormones play a critical role in the growth and development of the alimentary tract in vertebrates. Their effects are mediated by nuclear receptors as well as the cell surface receptor integrin αVß3. Systemic thyroid hormone levels are controlled via activation and deactivation by iodothyronine deiodinases in the liver and other tissues. Given that thyroid hormone signaling has been characterized as a major effector of digestive system growth and homeostasis, numerous investigations have examined its role in the occurrence and progression of cancers in various tissues of this organ system. The present review summarizes current findings regarding the effects of thyroid hormone signaling on cancers of the esophagus, stomach, liver, pancreas, and colon. Particular attention is given to the roles of different thyroid hormone receptor isoforms, the novel integrin αVß3 receptor, and thyroid hormone-related nutrients as possible protective agents and therapeutic targets. Future investigations geared towards a better understanding of thyroid hormone signaling in digestive system cancers may provide preventive or therapeutic strategies to diminish risk, improve outcome and avert recurrence in afflicted individuals.

Increased risk of gastrointestinal malignancy in patients with diabetes mellitus and correlations with anti-diabetes drugs: a nationwide population-based study in Taiwan.

OBJECTIVE: Although the major cause of morbidity and mortality in patients with diabetes mellitus (DM) is cardiovascular disease, DM is also associated with certain site-specific cancers. However, whether DM is associated with an increased risk of cancer of the digestive tract remains undetermined. A nationwide, population-based database in Taiwan was analyzed to explore the relationship between DM and cancer of the digestive organs. METHODS: From 2000 to 2007, a study cohort consisting of 39,515 patients with newly diagnosed diabetes without a previous diagnosis of gastrointestinal (GI) cancer was identified from the National Health Insurance Research Database in Taiwan. A control cohort of 79,030 age- and sex-matched non-diabetic subjects was selected to compare the occurrence of GI malignancies between the two groups. The association between the incidence of GI cancers and the use of glucose-lowering therapies was also investigated. RESULTS: During the 7-year follow-up period, GI cancers developed in 929 diabetic patients (2.35%) and 1,126 subjects (1.42%) in the comparison cohort. DM was associated with a 2.75-fold (95% confidence interval (CI), 2.51-3.02) higher risk of developing GI malignancy. Among GI cancers, the incidences of stomach (adjusted hazard ratio (HR), 1.49; 95% CI, 1.16-1.92), liver (adjusted HR, 2.65; 95% CI, 2.29-3.07), colon (adjusted HR, 1.58; 95% CI, 1.28-1.94) and pancreatic cancers (adjusted HR, 4.35; 95% CI, 2.93-6.47) were significantly increased in the patients with DM. An analysis of the effects of various glucose-lowering therapies in the diabetic patients revealed the use of α-glucosidase inhibitors to be associated with a lower risk of hepatic cancer (adjusted HR, 0.62; 95% CI, 0.4-0.94). Thiazolidinedione (TZD) treatment was associated with lower stomach (adjusted HR, 0.11; 95% CI, 0.02-0.82) and hepatic cancer risks (adjusted HR, 0.46; 95% CI, 0.29-0.73), while sulfonylurea use was associated with a lower colon cancer risk (adjusted HR, 0.74; 95% CI, 0.51-1.09) and a higher pancreatic cancer risk (adjusted HR, 2.36; 95% CI, 1.21-4.61). CONCLUSION: Patients with DM have an increased risk of GI malignancy that may be affected by the use of different categories of glucose-lowering therapies.

[Nrf2 as a chemoprevention target in gastrointestinal carcinoma].

Gastrointestinal tract carcinoma is one of the leading causes of cancer-related death in China. Chemoprevention has been considered as a potential approach to control this type of disease. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that protects cells from oxidative/electrophilic stresses by activating the expression of a battery of cytoprotective genes through the antioxidant response element (ARE). Recently, Nrf2 has emerged as a novel target for chemoprevention. Several natural or synthetic chemicals, which activate Nrf2/ARE signaling pathway, have showed effect in animal models, and promises in many ongoing clinical trials. This review summarizes the recent findings on the regulation of Nrf2/ARE signaling pathway, and the developments in both preclinical and clinical studies.

Inflammation-associated cancer development in digestive organs: mechanisms and roles for genetic and epigenetic modulation.

Chronic inflammation, regardless of infectious agents, plays important roles in the development of various cancers, particularly in digestive organs, including Helicobacter pylori-associated gastric cancer, hepatitis C virus-positive hepatocellular carcinoma, and colitis-associated colon cancers. Cancer development is characterized by stepwise accumulation of genetic and epigenetic alterations of various proto-oncogenes and tumor-suppressor genes. During chronic inflammation, infectious agents such as H pylori and hepatitis C virus as well as intrinsic mediators of inflammatory responses, including proinflammatory cytokines and reactive oxygen and nitrogen species, can induce genetic and epigenetic changes, including point mutations, deletions, duplications, recombinations, and methylation of various tumor-related genes through various mechanisms. Furthermore, inflammation also modulates the expressions of microRNAs that influence the production of several tumor-related messenger RNAs or proteins. These molecular events induced by chronic inflammation work in concert to alter important pathways involved in normal cellular function, and hence accelerate inflammation-associated cancer development. Among these, recent studies highlighted an important role of activation-induced cytidine deaminase, a nucleotide-editing enzyme essential for somatic hypermutation and class-switch recombination of the immunoglobulin gene, as a genomic modulator in inflammation-associated cancer development.