[Gastrointestinal tumour prevention strategies]. / Präventionsstrategien gastrointestinaler Tumoren.

Over the past few decades, substantial advancements have been achieved in the early detection and treatment of gastrointestinal oncological diseases. The survival rates of patients have significantly improved due to the expansion and enhancement of therapeutic and diagnostic options, leading to modifications in (neo-)adjuvant, perioperative, and palliative strategies, as well as the advent of personalized molecular therapy. Noteworthy progress has also been observed in primary, secondary, and tertiary prevention domains.Despite these advancements, gastrointestinal tumours continue to be a global health burden, with approximately 4 million new cases diagnosed annually. These constitute over a quarter of all tumour cases, with nearly one-third of all global tumour-related mortalities attributed to gastrointestinal tumours.Emerging evidence implicates aberrant differentiation of stem or progenitor cells in the pathogenesis of gastrointestinal tumour diseases. A confluence of clinically recognized risk factors, including high-fat diet, bile acid, microbiome alterations, and host factors, can instigate chronic inflammation. This disrupts stem cell homeostasis and precipitates malignant transformation. Consequently, environmental inflammation emerges as a critical risk factor warranting consideration in clinical cancer prevention and surveillance strategies.This review encapsulates the current understanding and recommendations in the prevention of selected gastrointestinal tumours, aiming to facilitate their integration into clinical practice. It underscores the need for continued research to further refine diagnostic and therapeutic strategies and improve patient outcomes.

Editorial for the Special Issue "Genetics and Genomics of Gastrointestinal Cancers: From Prevention to Treatment".

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Supplemental B-Vitamins and Risk of Upper Gastrointestinal Cancers in the Women's Health Initiative.

B-vitamins contribute to DNA synthesis, maintenance, and regulation. Few studies have examined associations of supplemental sources of B-vitamins with the incidence of upper gastrointestinal (GI) cancers [including gastric (GCA) and esophageal (ECA) cancers]; the only prior study to comprehensively examine such intakes reported potential elevated risks of ECA. We examined 159,401 postmenopausal women, ages 50-79 years at baseline, including 302 incident GCA and 183 incident ECA cases, over 19 years of follow-up within the Women's Health Initiative observational study and clinic trials. Adjusted Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) for associations of supplemental B-vitamins [riboflavin (B2), pyridoxine (B6), folic acid (B9), or cobalamin (B12)] with GCA and ECA risk, respectively. Although HRs were generally below 1.0, we observed no statistically significant associations between supplemental intakes of any of the evaluated B-vitamins with the risk of GCA or ECA. As the first prospective study to comprehensively assess these associations, our findings do not corroborate prior research indicating potential harm from supplemental B-vitamin intake for upper GI cancer risk. This study adds evidence that supplemental intakes of B-vitamins may be used by postmenopausal women without regard to their relationship with upper GI cancer risk.

Gut microbiome in gastrointestinal cancer: a friend or foe?

The impact of the gut microbiome on host health is becoming increasingly recognized. To date, there is growing evidence that the complex characteristics of the microbial community play key roles as potential biomarkers and predictors of responses in cancer therapy. Many studies have shown that altered commensal bacteria lead to cancer susceptibility and progression in diverse pathways. In this review, we critically assess the data for gut microbiota related to gastrointestinal cancer, including esophageal, gastric, pancreatic, colorectal cancer, hepatocellular carcinoma and cholangiocarcinoma. Importantly, the underlying mechanisms of gut microbiota involved in cancer occurrence, prevention and treatment are elucidated. The purpose of this review is to provide novel insights for applying this understanding to the development of new therapeutic strategies in gastrointestinal cancer by targeting the microbial community.

Role of Aspirin in Gastric Cancer Prevention.

The role of aspirin in cancer prevention has been well described for multiple cancers, with strong data for gastrointestinal cancers. Studies, primarily conducted in colorectal cancer, suggest that aspirin exerts its cancer-preventive effects through the inhibition of gastrointestinal inflammation. Compared with colorectal cancer, the role of aspirin in gastric cancer prevention is less well described, however it stands to reason that aspirin and/or other nonsteroidal anti-inflammatory drugs may inhibit gastric cancer progression through the inhibition of COX-2. As discussed in this issue of Cancer Prevention Research, aspirin may prevent gastric cancer, albeit it appears to exert a disparate effect in men and women, the reason for which remain unclear. These results expand upon prior studies by prospectively examining aspirin use at a wider range of doses and durations in non-Asian participants and lend support to observations from previously conducted studies in Asian populations. See related article, p. 265.

Safety and effectiveness of low-dose aspirin for the prevention of gastrointestinal cancer in adults without atherosclerotic cardiovascular disease: a population-based cohort study.

OBJECTIVE: To assess the association between low-dose aspirin and the incidence of colorectal cancer (CRC), gastric cancer (GC), oesophageal cancer (EC) and gastrointestinal bleeding (GIB) in adults without established atherosclerotic cardiovascular disease. DESIGN: Cohort study with propensity score matching of new-users of aspirin to non-users. SETTING: Clinical Data Analysis and Reporting System database, Hong Kong. PARTICIPANTS: Adults ≥40 years with a prescription start date of either low-dose aspirin (75-300 mg/daily) or paracetamol (non-aspirin users) between 1 January 2004 to 31 December 2008 without a history of atherosclerotic cardiovascular disease. MAIN OUTCOME MEASURES: The primary outcome was the first diagnosis of gastrointestinal cancer (either CRC, GC or EC) and the secondary outcome was GIB. Individuals were followed from index date of prescription until the earliest occurrence of an outcome of interest, an incident diagnosis of any type of cancer besides the outcome, death or until 31 December 2017. A competing risk survival analysis was used to estimate HRs and 95% CIs with death as the competing risk. RESULTS: After matching, 49 679 aspirin and non-aspirin users were included. The median (IQR) follow-up was 10.0 (6.4) years. HRs for low-dose aspirin compared with non-aspirin users were 0.83 for CRC (95% CI, 0.76 to 0.91), 0.77 for GC (95% CI, 0.65 to 0.92) and 0.88 for EC (95% CI, 0.67 to 1.16). Patients prescribed low-dose aspirin had an increased risk of GIB (HR 1.15, 95% CI, 1.11 to 1.20), except for patients prescribed proton pump inhibitors or histamine H2-receptor antagonists (HR 1.03, 95% CI, 0.96 to 1.10). CONCLUSION: In this cohort study of Chinese adults, patients prescribed low-dose aspirin had reduced risks of CRC and GC and an increased risk of GIB. Among the subgroup of patients prescribed gastroprotective agents at baseline, however, the association with GIB was attenuated.

Lipid-lowering drug adherence and combination therapy effects on gastrointestinal cancer in patients with dyslipidemia without diabetes: a retrospective cohort study in South Korea.

BACKGROUND: In aging populations, the number of people with high cholesterol levels is increasing. Appropriate management of high cholesterol levels with drugs such as statins may prevent secondary diseases. Despite many studies on the effects of statins on various types of cancer, the effectiveness of lipid-lowering therapy in preventing cancer remains controversial. This study aimed to evaluate its long-term effect on developing gastrointestinal (GI) cancer in patients with dyslipidemia. METHODS: This study used the National Health Insurance Sampling (NHIS) cohort data (2002-2015), which included patients with dyslipidemia without diabetes, and measured patients' adherence to lipid-lowering therapy using the medication possession ratio. We used the Cox proportional hazard ratio (HR) to identify the association between the continuity of lipid-lowering therapy and the risk of GI cancer. We also evaluated the association between a combination of lipid-lowering drugs and a reduced risk of GI cancer. RESULTS: A total of 49,351 patients were diagnosed with dyslipidemia, of which 579 were diagnosed with GI cancer. Patients with higher adherence to lipid-lowering therapy had a significantly reduced risk of GI cancer compared to patients without drugs, and high adherence was associated with a reduced incidence of all types of GI cancer. Specifically, the combination of statins and ezetimibe or fibrates appears to reduce GI cancer risk effectively. Overall, the continuity of lipid-lowering therapy had a protective effect on GI cancer in middle-aged and elderly patients with dyslipidemia compared to non-users. CONCLUSIONS: Our findings suggest that the continuity of lipid-lowering therapy is vital in patients with dyslipidemia. In addition, for individuals vulnerable to GI cancer, combination therapy may be associated with more effective protection against GI cancer. Healthcare providers need patient education and monitoring to improve drug adherence in patients with dyslipidemia.

Olive oil intake and cancer risk: A systematic review and meta-analysis.

BACKGROUND: Research evidence has established the beneficial effects of diet in cancer prevention; various epidemiological studies have suggested that olive oil component could play a role in decreasing cancer risk. This systematic review and meta-analysis aims to investigate the association between olive oil consumption, cancer risk and prognosis. METHODS: A systematic search was conducted in PubMed, EMBASE and Google Scholar databases (end-of-search: May 10, 2020). Pooled relative risk (RR) and 95% confidence intervals (95% CIs) were estimated with random-effects (DerSimonian-Laird) models. Subgroup analyses, sensitivity analyses and meta-regression analysis were also performed. RESULTS: 45 studies were included in the meta-analysis; 37 were case-control (17,369 cases and 28,294 controls) and 8 were cohort studies (12,461 incident cases in a total cohort of 929,771 subjects). Highest olive oil consumption was associated with 31% lower likelihood of any cancer (pooled RR = 0.69, 95%CI: 0.62-0.77), breast (RR = 0.67, 95%CI: 0.52-0.86), gastrointestinal (RR = 0.77, 95%CI: 0.66-0.89), upper aerodigestive (RR = 0.74, 95%CI: 0.60-0.91) and urinary tract cancer (RR = 0.46, 95%CI: 0.29-0.72). Significant overall effects spanned both Mediterranean and non-Mediterranean participants, studies presenting a multivariate and a univariate analysis and all subgroups by study quality. CONCLUSIONS: Olive oil consumption seems to exert beneficial actions in terms of cancer prevention. Additional prospective cohort studies on various cancer types and survivors, as well as large randomized trials, seem desirable.

Non-bacteria microbiome (virus, fungi, and archaea) in gastrointestinal cancer.

The gastrointestinal tract houses millions of microbes collectively referred to as the gut microbiome. The gut microbes comprise of bacteria, viruses, fungi, archaea, and microscopic eukaryotes, which co-evolved or colonize the gut forming complex symbiotic and mutualistic relationships. A state of homeostasis is required between host and gut microbiome relationship to maintain several host beneficial processes. Alterations in the taxonomic and functional composition of the gut microbes are associated with several human diseases including gastrointestinal cancers. Owed to their overwhelming abundance and ease of characterization, several studies focus on the role of bacteria in gastrointestinal cancers. There is however growing evidence that non-bacteria gut microbes are associated with the pathogenesis of gastrointestinal cancers. This review details the association of non-bacteria gut microbes including fungi, viruses, and archaea and their potential manipulation in the prevention and treatment of human gastrointestinal cancers.

Adherence to the new policy framework of the World Cancer Research Fund International in developing a policy package for the prevention of gastrointestinal cancers in Iran: a Delphi study.

BACKGROUND: Gastrointestinal cancers in Iran are among the major non-communicable diseases with a considerable burden on the health system. Changes in lifestyles as well as environmental factors have resulted in the emergence of these cancers. OBJECTIVE: To elicit and quantitatively verify experts' opinions regarding the potential public health impact, feasibility, economic impact, and budgetary impact of gastrointestinal cancer prevention policies in Iran. METHODS: Sixteen experts from Iran were recruited in an email-based, two-round Delphi study. In each round, a questionnaire of policy options for preventing gastrointestinal cancers, which adhered to the new policy framework of the World Cancer Research Fund International, was given to participants. In the first round, experts were asked to provide opinions for and against the policy options. The second round evaluated the policy options for their public health impact, feasibility, economic impact, and budgetary impact. RESULTS: A total of 32 policy options were organized based on three domains: health-enhancing environments, system changes, and behavior change communications. Of the 32 policy options, there were consensus in 31 (96%) and 30 (93%) options for public health impact and feasibility, respectively. On study completion, experts reached a consensus in 29 of 32 (90%) policy options for economic impact; only on 26 (81%) of these policy options did participants reached consensus for budgetary impact. CONCLUSION: Findings indicated that although nearly all policy options reached a consensus for their public health impact, some options are not feasible or do not appear to have an economic rationale for being implemented. Moreover, it is crucial to take into account the inter-sectoral collaboration between health and non-health sectors. Findings from this study can be helpful for health policymakers in identifying support for evidence-informed approaches regarding gastrointestinal cancer prevention.

[Prevention of gastrointestinal cancer]. / Prävention gastrointestinaler Tumore.

Throughout the past decades, considerable progress has been made in the (early) diagnosis and treatment of gastrointestinal cancers. However, the prognosis for advanced stages of gastrointestinal tumors remains limited for many patients and approximately one third of all tumor patients die as a result of gastrointestinal tumors. The prevention and early detection of gastrointestinal tumors is therefore of great importance.For this reason, we summarize the current state of knowledge and recommendations for the primary, secondary and tertiary prevention of esophageal, stomach, pancreas, liver and colorectal cancer in the following.

Potential Impact of Time Trend of Lifestyle Risk Factors on Burden of Major Gastrointestinal Cancers in China.

BACKGROUND & AIMS: China has the largest number of incident liver, esophageal, gastric, and colorectal cancer cases in 2020. Examining the time trend of relevant lifestyle risk factors would help project the trend of these gastrointestinal (GI) cancer incidence in China. METHODS: We estimated the time trend of the lifestyle factors based on the China Health and Nutrition Survey 1991 to 2011. We applied the comparative risk assessment method to estimate the population attributable fraction of GI cancers attributable to each risk factor. We also projected the prevalence of lifestyle factors and the associated burden of GI cancer from 2011 to 2031. RESULTS: In 2011, 56.5% of colorectal, 59.8% of gastric, 48.5% of esophageal, and 35.2% of liver cancer in China were attributable to the lifestyle risk factors under study. Smoking, sodium intake, low vegetable intake, and low fruit intake have improved over time but remained far from optimal and are expected to be responsible for 170,000, 35,000, 22,000, and 50,000 GI cancer cases in 2031, respectively. High body mass index, red and processed meat consumption, and low physical activity are expected to contribute increasingly more GI cancer, accounting for 142,000, 185,000, 60,000, and 53,000 cases in 2031, respectively. The estimated population attributable fraction for all risk factors in 2031 is 52.1%. CONCLUSIONS: Lifestyle risk factors have had an impact on the risk of GI cancer in China, and the impact is projected to increase. If everyone could adhere to the optimal lifestyle, half of all GI cancer events would be prevented by year 2031.

Molecular mechanisms underlying curcumin-mediated microRNA regulation in carcinogenesis; Focused on gastrointestinal cancers.

Curcumin is a bioactive ingredient found in the Rhizomes of Curcuma longa. Curcumin is well known for its chemopreventive and anti-cancer properties. Recent findings have demonstrated several pharmacological and biological impacts of curcumin, related to the control and the management of gastrointestinal cancers. Mechanistically, curcumin exerts its biological impacts via antioxidant and anti-inflammatory effects through the interaction with various transcription factors and signaling molecules. Moreover, epigenetic modulators such as microRNAs (miRNAs) have been revealed as novel targets of curcumin. Curcumin was discovered to regulate the expression of numerous pathogenic miRNAs in gastric, colorectal, esophageal and liver cancers. The present systematic review was performed to identify miRNAs that are modulated by curcumin in gastrointestinal cancers.

Guanylyl cyclase 2C (GUCY2C) in gastrointestinal cancers: recent innovations and therapeutic potential.

INTRODUCTION: Gastrointestinal (GI) cancers account for the second leading cause of cancer-related deaths in the United States. Guanylyl cyclase C (GUCY2C) is an intestinal signaling system that regulates intestinal fluid and electrolyte secretion as well as intestinal homeostasis. In recent years, it has emerged as a promising target for chemoprevention and therapy for GI malignancies. AREAS COVERED: The loss of GUCY2C signaling early in colorectal tumorigenesis suggests it could have a significant impact on tumor initiation. Recent studies highlight the importance of GUCY2C signaling in preventing colorectal tumorigenesis using agents such as linaclotide, plecanatide, and sildenafil. Furthermore, GUCY2C is a novel target for immunotherapy and a diagnostic marker for primary and metastatic diseases. EXPERT OPINION: There is an unmet need for prevention and therapy in GI cancers. In that context, GUCY2C is a promising target for prevention, although the precise mechanisms by which GUCY2C signaling affects tumorigenesis remain to be defined. Furthermore, clinical trials are exploring its role as an immunotherapeutic target for vaccines to prevent metastatic disease. Indeed, GUCY2C is an emerging target across the disease continuum from chemoprevention, to diagnostic management, through the treatment and prevention of metastatic diseases.

The relationship between gastrointestinal cancers and the microbiota.

The contribution of the microbiota to disease progression and treatment efficacy is often neglected when determining who is at the highest risk of developing gastrointestinal cancers or designing treatment strategies for patients. We reviewed the current literature on the effect of the human microbiota on cancer risk, prognosis, and treatment efficacy. We highlight emerging research that seeks to identify microbial signatures as biomarkers for various gastrointestinal cancers, and discuss how we could harness knowledge of the microbiome to detect, prevent, and treat these cancers. Finally, we outline further research needed in the field of gastrointestinal cancers and the microbiota, and describe the efforts required to increase the accuracy and reproducibility of data linking the microbiome to cancer.

Effectiveness of one-time endoscopic screening programme in prevention of upper gastrointestinal cancer in China: a multicentre population-based cohort study.

OBJECTIVES: To estimate the effectiveness of endoscopic screening programme in reducing incidence and mortality of upper gastrointestinal cancer in high risks areas of China. DESIGN: This multicentre population-based cohort study was conducted in six areas in China from 2005 to 2015. All permanent residents aged 40 to 69 years were identified as target subjects. We refer to those who were invited for screening collectively as the invited group. Of these, we classify those who were invited and undertook endoscopic screening as the screened group and those who were invited but did not accept screening as the non-screened group. Target subjects who were not invited to the screening were assigned to the control group. The effectiveness of the endoscopic screening and screening programme were evaluated by comparing reductions in incidence and mortality from upper gastrointestinal cancer in the screened and invited group with control group. RESULTS: Our cohort analysis included 637 500 people: 299 483 in the control group and 338 017 in the invited to screening group, 113 340 (33.53%) of whom were screened eventually. Compared with subjects in the control group, upper gastrointestinal cancer incidence and mortality decreased by 23% (relative risk (RR)=0.77, 95% CI 0.74 to 0.81) and 57% (RR=0.43, 95% CI 0.40 to 0.47) in the screened group, respectively, and by 14% (RR=0.86, 95% CI 0.84 to 0.89) and 31% (RR=0.69, 95% CI 0.66 to 0.72) in the invited group, respectively. CONCLUSION: Among individuals aged 40 to 69 years in high risk areas of upper gastrointestinal cancer, one-time endoscopic screening programme was associated with a significant decrease in upper gastrointestinal cancer incidence and mortality.

Current status of probiotics for prevention and management of gastrointestinal cancers.

INTRODUCTION: Gastrointestinal cancers contribute to a significant number of cancer- associated mortality. The gastrointestinal tract harbors a multitude of microorganisms, known as the microbiota. Recently, the microbiota is considered to be an accessory organ resulting in several health benefits. The microbiota is involved in almost all aspects of an individual ranging from managing behavior to controlling metabolism, immune status and the response to a disease. Researchers are observing the modulation of microbiota in almost every disease, including cancer. Probiotics are microorganisms that can help to alter the host microbiota toward a healthy state thus providing benefits from many diseases including cancer. AREAS COVERED: We explored the current status of the use of probiotics in cancer patients. Although probiotic bacteria can provide significant benefits to individuals suffering from cancer, the number of cancer-specific clinical products containing probiotics is not comparable to research studies showing their benefits. The lack of available products is due to several factors including a lack of risk assessment data of beneficial probiotics in cancer patients. EXPERT OPINION: Laboratory investigations indicate a huge potential of probiotics for the prevention and management of gastrointestinal cancer, but more clinical studies are required to support their application in clinical settings.