Risk Of Gastrointestinal Cancer Research Articles

Oral dysbiosis and risk of gastrointestinal cancers: A systematic review and meta-analysis of longitudinal studies.

Poor oral health and oral dysbiosis were found to be associated with cancers, especially of the gastrointestinal (GI)system. But the cause-and-effect relationship and the effect of the risk are not yet known due to scarcity of literature. Understanding such risk relationship can contribute to an integrated multi-disciplinary approach for GI cancer prevention. The aim of the present systematic review and meta-analysis is to assess the role of oral dysbiosis on increasing the risk of digestive system cancers. To evaluate the effect of poor oral health on increasing the risk of gastrointestinal cancers. We conducted a systematic search following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in databases PubMed, Elsevier, Wiley's online library and Web of Science from inception to February 2023 to include recent cohort studies that assessed the association between poor oral health and the risk of cancer. We assessed bias using the New Castle Ottawa scale. We used inferential statistics to describe the effect of oral dysbiosis on gastrointestinal cancers. We performed a sub-group analysis to assess the effect of oral conditions on individual cancers. We included 10 longitudinal studies in the meta-analysis. The overall effect size of poor oral health and GI cancer risk was hazard's ratio (HR) =1.30 (95% CI: [1.14, 1.46]) (p<0.001) (I2 = 68.78). Sub-group analysis indicated that poor oral health increases the risk of esophageal cancer HR=1.61 (95% CI: [1.37, 1.85]), stomach cancer HR=1.33 (95% CI: [1.08, 1.58]), pancreatic cancer HR=1.90 (95%CI; [1.29, 2.50]) and colorectal and hepatocellular carcinoma HR=1.16 (95% CI: [1.08, 1.23]). The meta-analysis indicated that poor oral health was significantly associated with increasing the risk of GI cancers.

The Burden of Overweight and Obesity-Associated Gastrointestinal Cancers in Low and Lower-Middle-Income Countries: A Global Burden of Disease 2019 Analysis

INTRODUCTION: Obesity is associated with cancer, including gastrointestinal (GI). Data from low (LICs) and lower-middle-income countries (MICs) are limited. METHODS: We utilized data from the Global Burden of Disease Study 2019 to determine the mortality from GI cancer risk of high body mass index (BMI) in these countries. RESULTS: Mortality rates of GI cancers from high BMI increased in LICs and lower MICs, while burdens decreased or remained stable in high and middle-income countries. DISCUSSION: The GI cancer-related burden from high BMI increased in LICs and lower MICs, necessitating a concerted effort to tackle the obesity pandemic.

Bile Acid Diarrhea is Associated with an Increased Incidence of Gastrointestinal Cancers.

Bile acid diarrhea (BAD) is an underrecognized and socially debilitating disease caused by high concentrations of bile acids in the colon. Bile acids directly and indirectly promote carcinogenesis. Here, we investigated if individuals with BAD have an increased risk of gastrointestinal (GI) cancers. By using the Danish health registries, adult individuals with BAD were identified by international classification of disease 10th revision (ICD10) code K90.8 or referral to the diagnostic ⁷⁵selenium-homotaurocholic acid test followed by prescription of a bile acid sequestrant within 365 days (n=5,245). Age and sex-matched individuals without BAD were included for comparison (n=52,450). We analyzed the cumulative incidence of GI cancers after BAD diagnosis and the odds ratios (ORs) of GI cancer eight and 15 years before BAD diagnosis/matching. Cumulative incidence of GI cancer six years after BAD diagnosis/matching was 1.6% in the BAD group and 1.1% in controls (p=0.01). The ORs of total GI cancer eight and 15 years before BAD diagnosis were 6.16 (5.08-7.48) and 5.19 (4.28-6.29), respectively. Furthermore, 47 individuals with BAD (0.9%) and 250 (0.5%) controls died of GI cancer. This nationwide cohort study indicates an association between BAD and GI cancers. We found both a higher incidence of GI cancer after BAD diagnosis compared with controls and increased OR of GI cancer before BAD diagnosis. Bearing in mind the underdiagnosis of BAD, the delay of BAD diagnosis, and the carcinogenic effect of bile acids, these findings warrant further investigations of the risk of GI cancer in individuals with BAD.

The current infection with Helicobacter pylori and association with upper gastrointestinal lesions and risk of upper gastrointestinal cancer: Insights from multicenter population-based cohort study.

The relationship between Helicobacter pylori (H. pylori) infection and upper gastrointestinal (UGI) cancers is complex. This multicenter, population-based cohort study conducted in seven areas in China aimed to assess the correlation between current H. pylori infection and the severity of UGI lesions, as well as its association with the risk of gastric cancer (GC) and esophageal cancer (EC). From 2015 to 2017, 27,085 participants (aged 40-69) completed a standardized questionnaire, and underwent a 13C-urea breath test. Then a subset underwent UGI endoscopy to assess the UGI lesion detection rates. All individuals were followed up until December 2021 to calculate the hazard ratios (HRs) for UGI cancers. H. pylori infection prevalence was 45.9%, and among endoscopy participants, 22.2% had gastric lesions, 19.2% had esophageal lesions. Higher detection rates of gastric lesions were noted in the H. pylori-positive population across all lesion severity levels. Over a median follow-up of 6.3 years, 104 EC and 179 GC cases were observed, including 103 non-cardia gastric cancer (NCGC) cases and 76 cardia gastric cancer (CGC) cases. H. pylori-infected individuals exhibited a 1.78-fold increased risk of GC (HR 1.78, 95% confidence interval [CI] 1.32-2.40) but no significant increase in EC risk (HR 1.07, 95% CI 0.73-1.57). Notably, there was a higher risk for both NCGC and CGC in H. pylori-infected individuals. This population-based cohort study provides valuable evidence supporting the association between current H. pylori infection and the risk of both NCGC and CGC. These findings contribute to the empirical basis for risk stratification and recommendations for UGI cancer screening.

Understanding Elderly Chinese Cancer Patients in a Multicultural Clinical Setting: Embracing Mortality and Addressing Misperceptions of Vulnerability.

Chinese patients face higher risks of gastrointestinal (GI) cancers and greater cancer-related deaths than Canadian-born patients. The older population encounters barriers to quality healthcare, impacting their well-being and survival. Previous studies highlighted Chinese immigrant perceptions of not requiring healthcare support. During the COVID-19 pandemic, their underutilization of healthcare services garnered attention. The present study explores the experiences of older Chinese cancer patients to improve culturally sensitive cancer care. A total of twenty interviews carried out in Cantonese and Mandarin were conducted with Chinese immigrants, aged 60 or above, diagnosed with Stage 3 or 4 GI cancer. These interviews were transcribed verbatim, translated, and subjected to qualitative descriptive analysis. Among older Chinese immigrant patients, a phenomenon termed "Premature Acceptance: Normalizing Death and Dying" was observed. This involved four key themes: 1. acceptance and letting go, 2. family first, 3. self-sufficiency, and 4. barriers to supportive care. Participants displayed an early acceptance of their own mortality, prioritizing family prosperity over their own quality of life. Older Chinese patients normalize the reality of facing death amidst cancer. They adopt a pragmatic outlook, acknowledging life-saving treatments while willingly sacrificing their own support needs to ease family burdens. Efforts to enhance health literacy require culturally sensitive programs tailored to address language barriers and differing values among this population. A strengths-based approach emphasizing family support and practical aspects of care may help build resilience and improve symptom management, thereby enhancing their engagement with healthcare services.

VEGF-2578C/A, -460T/C Polymorphisms and Gastrointestinal Tract Cancer Risk: An Updated Meta-Analysis.

Functional polymorphisms in the vascular endothelial growth factor (VEGF) alter the susceptibility toward different gastrointestinal tract (GIT) cancers. In this study, we explored the association of VEGF-2578C/A and VEGF-460T/C polymorphisms with esophageal cancer (EC) risk. In total, 330 patients with EC and 330 controls for VEGF-2578C/A polymorphism and 316 patients with EC and 316 controls for VEGF-460T/C polymorphism were genotyped. AA genotype (p = 0.01) and A allele (p = 0.02) of VEGF-2578C/A and CC genotype (p = 0.04) and C allele (p = 0.04) of VEGF-460T/C polymorphism were significantly associated with an increased risk of EC. VEGF-2578C/A and VEGF-460T/C polymorphisms have been studied in different GIT cancers, but results are inconclusive. Therefore, we performed a meta-analysis to assess the association of these polymorphisms with the risk of GIT cancers. The PubMed, ScienceDirect, and Google Scholar databases were used to search the articles. Twenty-one studies on VEGF-2578C/A and 20 studies on VEGF-460T/C polymorphism were included in this meta-analysis. VEGF-2578C/A polymorphism was associated with the decreased risk of GIT cancer in the overall population under the overdominant model (p = 0.009). A significant association of VEGF-2578C/A polymorphism with GIT cancer risk has been observed in the middle easterners, Caucasians, and Asians under different genetic models. VEGF-460T/C polymorphism was significantly associated with an increased risk of GIT cancers in Caucasians. Stratification of the data on the basis of cancer type showed a significant association of VEGF-2578C/A polymorphism with the risk of gallbladder cancer, whereas VEGF-460T/C polymorphism was associated with the risk of hepatocellular cancer, gastric cancer, and colorectal cancer. Our meta-analysis suggested that VEGF-2578C/A and VEGF-460T/C polymorphisms were associated with GIT cancer risk.

A population-based cohort study of longitudinal change of high-density lipoprotein cholesterol impact on gastrointestinal cancer risk

High-density Lipoprotein Cholesterol (HDL-C) levels have been associated with cancer. In this observational population-based cohort study using data from the Korean National Health Insurance Service system, we investigate the impact of longitudinal changes in HDL-C levels on gastrointestinal cancer risk. Individuals who underwent health examinations in 2010 and 2014 were followed-up through 2021. Among 3.131 million, 40696 gastric, 35707 colorectal, 21309 liver, 11532 pancreatic, 4225 gallbladder, and 7051 biliary cancers are newly detected. The persistent low HDL-C group increases the risk of gastric, liver, and biliary cancer comparing to persistent normal HDL-C group. HDL-C change from normal to low level increases the risk for gastric, colorectal, liver, pancreatic, gallbladder, and biliary cancers. Effects of HDL-C change on the gastrointestinal cancer risk are also modified by sex and smoking status. HDL-C changes affect the gastric and gallbladder cancer risk in age ≥60 years and the pancreatic and biliary cancer risk in age <60 years. Here, we show persistently low HDL-C and normal-to-low HDL-C change increase gastrointestinal cancer risk with discrepancies by sex, smoking status, and age.

The association between pre-existing heart failure and cancer incidence: A systematic review and meta-analysis

Introduction and objectivesCardiovascular diseases (CVD) and cancer are some of the most recognized causes of mortality and morbidity worldwide. Cancer is the second leading cause of death in heart failure (HF) populations. Recent studies have hypothesized that HF might promote the development and progression of cancer. We aim to analyze and discuss the most recent evidence on the relationship between HF and cancer development. MethodsFrom inception to November 2022, we searched PubMed, Web of Science and ClinicalTrials.gov for relevant articles on patients with HF and a subsequent cancer diagnosis that reported outcomes of overall and site-specific cancer incidence, or mortality. ResultsOf 2401 articles identified in our original search, 13 articles met our criteria. Studies reporting risk rate estimates were summarized qualitatively. Studies reporting hazard ratios (HRs), or relative risks were combined in a meta-analysis and revealed that HF was associated with an increased overall cancer incidence with a HR=1.30 (95% CI: 1.04–1.62) compared with individuals without HF. Subgroup analyses by cancer type revealed increased risk for lung cancer (HR=1.87; 95% CI: 1.28–2.73), gastrointestinal cancer (HR=1.22; 95% CI: 1.03–1.45), hematologic cancer (HR=1.60; 95% CI: 1.23–2.08) and female reproductive cancer (HR=1.67; 95% CI: 1.27–2.21). Mortality from cancer was higher in HF patients compared with non-HF subjects with a HR=2.17 (95% CI: 1.23–3.84). ConclusionsOur systematic review and meta-analysis revealed that HF may result in a subsequent increase in cancer incidence as well as in cancer-related mortality. The most common cancer subtypes in HF patients were lung, female reproductive system, and hematologic cancers. Further research is needed to understand this association better and to provide the best cardiological and oncological care.

Use of 5-alpha reductase inhibitors and risk of gastrointestinal cancers in men with benign prostatic hyperplasia: A population-based cohort study.

Pre-clinical evidence suggests that 5-alpha reductase inhibitors (5ARi's), prescribed in the treatment of benign prostatic hyperplasia, reduce colorectal and gastro-oesophageal cancer incidence via action on the male hormonal pathway. However, few studies to date have investigated this association at the population level. Our study aimed to investigate the risk of colorectal and gastro-oesophageal cancers with the use of 5ARi's. We conducted a retrospective cohort study of new users of 5ARi's and alpha-blockers among patients with benign prostatic hyperplasia in the UK Clinical Practice Research Datalink. Patients were followed until a first ever diagnosis of colorectal or gastro-oesophageal cancer, death from any cause or end of registration with the general practice or 31st of December 2017. Cox proportional hazards models with inverse probability of treatment weights were used to calculate weighted hazard ratios (HR) and 95% confidence intervals (CIs) of incident colorectal cancer or gastro-oesophageal cancer associated with the use of 5ARi's compared to alpha-blockers. During a mean follow-up of 6.6 years, we found no association between the use of 5ARi's and colorectal (HR: 1.13, 95% CI 0.91-1.41) or gastro-oesophageal (HR 1.14, 95% CI 0.76-1.63) cancer risk compared to alpha-blockers. Sensitivity analysis showed largely consistent results when varying lag periods, using multiple imputations, and accounting for competing risk of death. Our study found no association between the use of 5ARi's and risk of colorectal or gastro-oesophageal cancer in men with benign prostatic hyperplasia.

Sodium-glucose cotransporter 2 inhibitors and cancer: a systematic review and meta-analysis.

The effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cancer has yet to be fully elucidated. This systematic review and meta-analysis investigated the effects of SGLT2 inhibitors on cancer. We searched the PubMed and ClinicalTrials.gov databases up to July 15, 2023, to identify eligible randomized, double-blind, placebo-controlled trials that lasted at least ≥24weeks. The primary outcome was the overall cancer incidence, and the secondary outcomes were the incidences of various types of cancer. We used the Mantel-Haenszel method, fixed effects model, risk ratio (RR) and 95% confidence interval (CI) to analyze dichotomous variables. Subgroup analysis was performed based on the SGLT2 inhibitor type, baseline conditions, and follow-up duration. All meta-analyses were performed using RevMan5.4.1 and Stata MP 16.0. A total of 58 publications (59 trials) were included, comprising 113,909 participants with type 2 diabetes mellitus and/or chronic kidney disease and/or high cardiovascular risk and/or heart failure (SGLT2 inhibitor group, 63864; placebo group, 50045). Compared to the placebo SGLT2 inhibitors did not significantly increase the overall incidence of cancer (RR 1.01; 95% CI 0.94-1.08; p = 0.82). However, ertugliflozin did significantly increase the overall incidence of cancer (RR 1.29; 95% CI 1.01-1.64; p = 0.04). SGLT2 inhibitors did not increase the risks of bladder or breast cancer. However, dapagliflozin did significantly reduce the risk of bladder cancer by 47% (RR 0.53; 95% CI 0.35-0.81; p = 0.003). SGLT2 inhibitors had no significant effect on the risks of gastrointestinal, thyroid, skin, respiratory, prostate, uterine/endometrial, hepatic and pancreatic cancers. Dapagliflozin reduced the risk of respiratory cancer by 26% (RR 0.74; 95% CI 0.55-1.00; p = 0.05). SGLT2 inhibitors (particularly mediated by dapagliflozin and ertugliflozin but not statistically significant) were associated with a greater risk of renal cancer than the placebo (RR 1.39; 95% CI 1.04-1.87; p = 0.03). SGLT2 inhibitors did not significantly increase the overall risk of cancer or the risks of bladder and breast cancers. However, the higher risk of renal cancer associated with SGLT2 inhibitors warrants concern.

Abstract 3436: Circadian rhythm dysregulation with risk of gastrointestinal cancers: A large-scale prospective analysis

Abstract Introduction: The incidence of multiple gastrointestinal (GI) cancers has been rising among younger adults with unknown etiology. Circadian rhythm dysregulation due to increasing exposures to artificial lighting, irregular work hours, and frequent travel, has been recently linked with multiple diseases. Disruption of the circadian clock drives Apc LOH to hyperactivate Wnt signaling and enhances MYC-dependent glycolytic metabolism to accelerate colorectal cancer progression. However, the association between circadian rhythm dysregulation, quantified by relative amplitude (RA)–a parameter derived from rest-activity patterns, and risk of colorectal and other GI cancers has not been evaluated in epidemiologic studies. Methods: We prospectively examined the associations between RA and risk of incident GI cancers among 87,653 UK Biobank participants who wore an Axivity AX3 triaxial accelerometer over 7 days (2013-15) with follow-up to 2021. RA was derived and averaged across all valid days, using the difference between the mean activity levels during the most active 10-hour period and the least active 5-hour period. Cox models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). Results: During 512,074 person-years, 1,079 incident GI cancer cases occurred. After multivariable adjustment, lower RA was associated with an increased risk of overall GI cancer (RR per SD [standard deviation] = 1.12, 95% CI 1.04-1.21, P for trend = 0.01). Compared to individuals in the highest tertile (T1), those with RA in the lowest tertile (T3) had a 25% increased risk of overall GI cancer (RR = 1.25, 95% CI 1.05-1.50). The positive associations with GI cancers were mainly driven by gastric cancer (RR per SD = 1.33, 95% CI 1.02-1.74, P for trend= 0.04) and colon cancer (RR per SD = 1.13, 95% CI 1.00-1.28, P for trend = 0.03). Conclusion: In this large-scale, prospective analysis of accelerometer data, circadian rhythm dysregulation was associated with subsequent risk of GI cancers, primarily gastric and colon cancer. To our knowledge, this is among the first population-based studies reporting the positive link between circadian rhythm dysregulation with cancer risk. Citation Format: Yi Kang, Shinghei Mok, Xiaoyu Zong, Yin Cao. Circadian rhythm dysregulation with risk of gastrointestinal cancers: A large-scale prospective analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3436.

Abstract 2173: Effect of colored fruits and vegetables intake on gastrointestinal cancer risk: A prospective cohort study

Abstract Background and Aim: Diverse antioxidant compounds found in colored fruits and vegetables have been linked to various health benefits. While anthocyanins, present in purple, red, and blue pigments, and chlorophyll, responsible for green pigments, are recognized for their antioxidant properties, limited evidence exists regarding their preventive effects on gastrointestinal (GI) cancers. In the year 2020, GI cancers constituted 29% of global cancer cases. To address this gap, this prospective cohort study investigates the association between the intake of colored fruits and vegetables and the risk of GI cancer in Korea. Methods: The Cancer Screenee Cohort, comprising adults undergoing check-ups at the National Cancer Center Korea, was analyzed for GI cancer cases diagnosed between October 16, 2007, and December 31, 2020. Of the 10,741 eligible participants, 208 developed GI cancer and 10,533 did not. General and validated semi-quantitative food frequency questionnaires were used to collect demographic data and measure dietary intake. Fruit and vegetable intake (g/day) were categorized into four groups (white, green, orange/yellow, and red/purple) based on the color of the edible parts. Analyses were conducted on total fruits/vegetables, total fruits, total vegetables, and fruits/vegetables in each color category. The intake was divided into quintiles to compare the effects of low and high intake. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). HRs were adjusted for variables, including age, gender, body mass index, smoking status, alcohol drinking, education, occupation, first-degree family history of any cancer, and marital status. Results: High total fruit and vegetable intake was associated with reduced GI cancer risk (HR = 0.64, 95% CI: 0.42-0.98, p for trend = 0.022). No significant associations were found for total fruits, total vegetables, fruits and vegetables together and separately in green and orange/yellow colors in this study. However, a higher intake of white fruits and vegetables was found to be effective in preventing cancer with adjusted HRs (HR = 0.51, 95% CI: 0.31-0.85, p for trend = 0.019). Similarly, the inverse association was observed in red and purple vegetables with adjusted HRs (HR = 0.52, 95% CI: 0.32-0.84, p for trend = 0.022). Conclusions: This cohort study suggests that the consumption of fruits and vegetables in white color, as well as vegetables in red and purple colors, may have a potential protective effect against GI cancer. Key Words: Gastrointestinal (GI) cancer; fruits and vegetables; colors of fruits and vegetables; color food; cohort studies; Korea Citation Format: Yujin Cho, Jeonghee Lee, Madhawa Gunathilake, Jeongseon Kim. Effect of colored fruits and vegetables intake on gastrointestinal cancer risk: A prospective cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2173.

Association of glucose-lowering drug target and risk of gastrointestinal cancer: a mendelian randomization study

Background & AimsGlucose-lowering drug is associated with various cancers, but the causality with gastrointestinal cancer risk is rarely reported. We aimed to explore the causality between them in this Mendelian randomization (MR) study.MethodsTwo-sample MR, summary-data-based (SMR), mediation MR, and colocalization analyses was employed. Ten glucose-lowering drug targets (PPARG, DPP4, GLP1R, INSR, SLC5A2, ABCC8, KCNJ11, ETFDH, GPD2, PRKAB1) and seven types of gastrointestinal cancer (anal carcinoma, cardia cancer, gastric cancer, hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), pancreatic cancer, rectum cancer) were included. Patients with gastrointestinal cancers from six different large GWAS databases, including the UK Biobank and Finnish cohorts were incorporated, for discovery and external validation. Meta-analysis was employed to integrate the results from both discovery and validation cohorts, thereby ensuring the reliability of findings.ResultsABCC8/KCNJ11 were associated with pancreatic cancer risk in both two-sample MR (odds ratio (OR): 15.058, per standard deviation unit (SD) change of glucose-lowering durg target perturbation equivalent to 1 SD unit of HbA1c lowering; 95% confidence interval (95% CI): 3.824–59.295; P-value = 0.0001) and SMR (OR: 1.142; 95% CI: 1.013–1.287; P-value = 0.030) analyses. The mediation effect of body mass index (OR: 0.938; 95% CI: 0.884–0.995; proportion of mediation effect: 3.001%; P-value = 0.033) on ABCC8/KCNJ11 and pancreatic cancer was uncovered. Strong connections of DPP4 with anal carcinoma (OR: 0.123; 95% CI: 0.020–0.745; P-value = 0.023) and ICC (OR: 7.733; 95% CI: 1.743–34.310; P-value = 0.007) were detected. PPARG was associated with anal carcinoma (OR: 12.909; 95% CI: 3.217–51.795; P-value = 0.0003), HCC (OR: 36.507; 95% CI: 8.929-149.259; P-value < 0.0001), and pancreatic cancer (OR: 0.110; 95% CI: 0.071–0.172; P-value < 0.0001). SLC5A2 was connected with pancreatic cancer (OR: 8.096; 95% CI: 3.476–18.857; P-value < 0.0001). Weak evidence indicated the connections of GLP1R, GPD2, and PRKAB1 with anal carcinoma, cardia cancer, ICC, and rectum cancer. In addition, the corresponding results were consistently validated in both the validation cohorts and the integrated outcomes.ConclusionsSome glucose-lowering drugs were associated with gastrointestinal cancer risk, which might provide new ideas for gastrointestinal cancer treatment.

Cancer risk according to fasting blood glucose trajectories: a population-based cohort study

IntroductionDiabetes mellitus is known to increase the risk of cancer. Fasting blood glucose (FBG) levels can be changed over time. However, the association between FBG trajectory and cancer risk has...

Occupational exposure to silica and risk of gastrointestinal cancers: a systematic review and meta-analysis of cohort studies.

Although silica is a proven lung carcinogen, there is no convincing evidence linking crystalline silica to gastrointestinal malignancies. We detailedly searched studies on the link between gastrointestinal malignancies and occupational silica exposure. Studies published between 1987 and 2023 were found by searching PubMed, Scopus, Cochrane Library, and Web of Science databases. Further studies were included from reference searching. We conducted a meta-analysis of the incidence and mortality of gastrointestinal malignancies and occupational silica exposure. We computed pooled-risk estimates using random effects models. Egger's regression asymmetry test and a funnel plot were used to identify publication bias. Moreover, sensitivity analysis and subgroup analysis were out. We identified 40 research with individuals from 13 different countries. The results indicate that occupational silica exposure raises the risk of gastric and esophageal cancer incidence, with pooled standardized incidence ratio of 1.35 (95% CI 1.21-1.51, p < 0.001), 1.31 (95% CI 1.04-1.65, p = 0.023), respectively, but there was a lack of statistically significant relationship between standardized mortality ratio. In addition, we found that silica exposure did not increase the risk of colorectal and pancreatic cancers. Occupational silica exposure was found to increase the risk of liver cancer, with pooled SIR and SMR of 1.19 (95% CI 1.04-1.35, p = 0.009), 1.24 (95% CI 1.03-1.49, p = 0.026), respectively. We discovered a link between occupational silica exposure and gastrointestinal malignancies, with cancers of the liver, stomach, and esophagus being the most prevalent. Colorectal and pancreatic cancer were not linked to occupational silica exposure.

Role of NADPH Quinone Reductase 1 (NQO1) Polymorphism in Prevention, Diagnosis, and Treatment of Gastrointestinal Cancers.

Most cancer deaths are related to gastrointestinal (GI) cancers. Several environmental and genetic factors are effective in the occurrence of GI cancers, such as esophageal, stomach, colorectal, liver, and pancreatic cancers. In addition to risk factors related to lifestyle, reactive oxygen species (ROS) also play a role in GI cancers, and an increase in the amount of free radicals can lead to oxidative stress and increase the probability of malignancies. NQO1 is part of the body's antioxidant defense system that protects cells against mutagenesis and carcinogenesis. NQO1 is responsible for reducing quinones to hydroquinone and preventing the generation of ROS by catalyzing the reaction. The existence of single nucleotide polymorphisms (SNPs) of NADPH Quinone Reductase 1 (NQO1), such as 609C>T NQO1, leads to a decrease in NQO1 enzyme activity. Some NQO1 polymorphisms may increase the risk of gastrointestinal cancer. So, the C609T polymorphism in the NQO1 gene has been found to be effective in causing gastrointestinal cancers. On the other hand, it is very important to know the role of biomarkers in the prognosis and management of cancer treatment. Therefore, this study investigated the role of NQO1 as a biomarker in the management of gastrointestinal cancers (prevention, diagnosis and treatment).

Association of metformin use and cancer incidence: a systematic review and meta-analysis.

Metformin is among the most widely used antidiabetics medications because of its minimal toxicity, favorable safety profile, availability, and low cost. In addition to its role in diabetes management, metformin may reduce cancer risk. We conducted a comprehensive systematic review and meta-analysis to investigate the association between metformin use and cancer risk, with evaluation by specific cancer type when possible. Applicable studies were identified in PubMed/MEDLINE, Embase, Cochrane Library, Web of Science, and Scopus from inception through March 7, 2023, with metformin use categorized as "ever" or "yes" and a cancer diagnosis as the outcome. Article quality was evaluated using National Heart, Lung, and Blood Institute guidelines, and publication bias was evaluated using the Egger test, Begg test, and funnel plots. Pooled relative risk (RR) estimates were calculated using random-effects models, and sensitivity analysis was completed through leave-one-out cross-validation. We included 166 studies with cancer incidence information in the meta-analysis. Reduced risk for overall cancer was observed in case-control studies (RR = 0.55, 95% confidence interval [CI] = 0.30 to 0.80) and prospective cohort studies (RR = 0.65, 95% CI = 0.37 to 0.93). Metformin use was associated with reduced gastrointestinal (RR = 0.79, 95% CI = 0.73 to 0.85), urologic (RR = 0.88, 95% CI = 0.78 to 0.99), and hematologic (RR = 0.87, 95% CI = 0.75 to 0.99) cancer risk. Statistically significant publication bias was observed within the studies (Egger P < .001). Metformin may be associated with a decreased risk of many cancer types, but high heterogeneity and risk of publication bias limit confidence in these results. Additional studies in populations without diabetes are needed to better understand the utility of metformin in cancer prevention.

Inflammatory response in gastrointestinal cancers: Overview of six transmembrane epithelial antigens of the prostate in pathophysiology and clinical implications.

Chronic inflammation is known to increase the risk of gastrointestinal cancers (GICs), the common solid tumors worldwide. Precancerous lesions, such as chronic atrophic inflammation and ulcers, are related to inflammatory responses in vivo and likely to occur in hyperplasia and tumorigenesis. Unfortunately, due to the lack of effective therapeutic targets, the prognosis of patients with GICs is still unsatisfactory. Interestingly, it is found that six transmembrane epithelial antigens of the prostate (STEAPs), a group of metal reductases, are significantly associated with the progression of malignancies, playing a crucial role in systemic metabolic homeostasis and inflammatory responses. The structure and functions of STEAPs suggest that they are closely related to intracellular oxidative stress, responding to inflammatory reactions. Under the imbalance status of abnormal oxidative stress, STEAP members are involved in cell transformation and the development of GICs by inhibiting or activating inflammatory process. This review focuses on STEAPs in GICs along with exploring their potential molecular regulatory mechanisms, with an aim to provide a theoretical basis for diagnosis and treatment strategies for patients suffering from these types of cancers.

Insulin resistance and impaired insulin secretion and gastrointestinal cancer risk in Korean adults: Preliminary results from Korean Genome and Epidemiology study.

761 Background: To date, few studies conducted on the effect of insulin resistance or insulin secretory function on cancer risk in non-diabetic population. This study evaluated whether insulin resistance and/or insulin secretory function affect gastrointestinal cancer risk in the Korean population. Methods: We analyzed data from Korean Genome and Epidemiology Study, Korea Association Resource dataset. It consists of 10,030 participants aged 40-69y observed from 2001 to 2018. The risk of all cancers, and gastrointestinal cancers were assessed. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and Homeostasis Model Assessment of Beta-cell function (HOMA-β) were used as indicators of insulin resistance and insulin secretory function. Results: In the final dataset, 8,649 individuals without previous history of any cancers were included. During an average follow-up of 15 years, 415 subjects (4.8%) developed cancers. Compared to the low HOMA-IR/high HOMA-β group (reference), diabetic patients had the highest risk of overall cancers, followed by high HOMA-IR/low HOMA-β group (Adjusted hazard ratio[95% confidence interval]: 1.74 [1.11 - 2.75] and 1.40 [0.96 – 2.06], respectively) Among gastrointestinal cancers, the risk of gastric cancer was higher in the low HOMA-IR/low HOMA-β and high HOMA-IR/high HOMA-β groups (1.92 [1.06 - 3.47] and 2.27 [1.26 - 4.06], respectively) When further analyzed by HOMA-β stratified by quartiles, the lowest quartile (Q1) showed an increased risk of gastric cancer compared to the highest-quartile (Q4; 1.84 [0.98 – 3.46], p = 0.06) In contrast, no significant results were observed regarding the colorectal cancer risk, when analyzed based on HOMA-IR and HOMA-β. However, when further analyzed by HOMA-IR stratified by quartiles, the highest quartile (Q4) exhibited a significantly elevated colorectal cancer risk compared to the lowest quartile (Q1; 2.14 [1.11 - 4.11], P for trend = 0.04). Conclusions: Insulin resistance and impaired insulin secretion function may increase the risk of cancer, but the underlying mechanisms may differ by cancer type.

Association of Various Viral Infections with the Risk of Gastrointestinal Cancers in the Iranian Population

Association of Various Viral Infections with the Risk of Gastrointestinal Cancers in the Iranian Population