Risk Factor For Gastrointestinal Cancers Research Articles

Anaerobic gram-negative rod bacteremia as a marker of gastrointestinal cancer in Japanese patients: a single-center retrospective study.

Gram-negative rod (GNR) bacteremia has been suggested as a clinical marker of occult cancer; however, no studies are available in this regard in the Japanese population. Here, we investigated the risk factors for gastrointestinal cancer with GNR bacteremia. Patients with GNR bacteremia admitted to St. Luke's International Hospital between January 2011 and July 2021 were included. The clinical data of patients with and without cancer, 1 year before and after GNR bacteremia diagnosis, were compared. Univariate analysis was performed using χ2 and Fisher's exact tests for categorical variables and the Mann-Whitney U test for continuous variables, while multivariable analysis was performed using logistic regression analysis, and a P of <0.05 was considered statistically significant. Of 2,296 GNR bacteremia-positive patients, 96 were associated with gastrointestinal cancer, and univariate analysis showed significant differences between the gastrointestinal cancer and comparison groups in terms of mean body mass index (BMI; 20.5 vs. 21.8 kg/m2), Enterobacterales detection (64.6% vs. 81.3%), and anaerobic GNR detection (24.0% vs. 8.5%). Thirty-five (36%) and 61 (64%) patients had upper and lower gastrointestinal cancer, respectively. There were 23 patients with anaerobic GNR bacteremia related to 24 strains (upper and lower gastrointestinal cancer, 5 and 18 cases, respectively). Multivariate analysis identified anaerobic GNR [odds ratio, 3.440; 95% confidence interval (CI): 2.085-5.675, P<0.001] as a significant risk factor for cancer. Anaerobic GNR in blood cultures may be a risk factor for gastrointestinal cancer. Therefore, it is necessary consider cancer workup, such as endoscopy, for patients with anaerobic GNR bacteremia.

Identifying potential risk factors associated with gastrointestinal tract cancers: &amp;nbsp;A case-control study in Turkey

&lt;b&gt;Objective: &lt;/b&gt;Gastrointestinal cancers have different risk factors. However, it was clearly thought that the risk factors of these cancers should be determined by a case-control studies. The study aims to determine the potential risk factors associated with gastrointestinal cancers with a case-control study design.&lt;br /&gt; &lt;b&gt;Material and methods:&lt;/b&gt; This case-control study was conducted with a total of 620 people applied to Department of General Surgery of two hospital in Turkey. The case group consisted of 310 patients diagnosed with gastrointestinal tract cancers. The control group consisted of 310 subjects without any history of cancer including gastrointestinal cancers. The data were collected with the Patient Identification Form including socio-demographic characteristics, and risk factors for gastrointestinal tract cancers.&lt;br /&gt; &lt;b&gt;Results:&lt;/b&gt; The mean age of the case and control groups were 58.9±12.9 and 50.0±10.0, respectively. Although there was statistically significant differences in several factors compared, multivariate analysis identified male gender (OR=1.729, p=0.02), higher age (OR=1.068, p&amp;lt;0.001), low body mass index (OR=1.110, p&amp;lt;0.001), high number of children (OR=1.563, p&amp;lt;0.001), cancer history in the family (OR=4.444, p&amp;lt;0.001) and the presence of other chronic diseases (OR=6.314, p&amp;lt;0.001) as risk factors. Mostly vegetable consumption (OR=2.923, p&amp;lt;0.001) was also found to be a lower risk factor for gastrointestinal cancers.&lt;br /&gt; &lt;b&gt;Conclusion:&lt;/b&gt; According to this study; age, gender, body mass index, number of children, family history of cancer, chronic diseases were among risk factors for gastrointestinal tract cancers. Vegetable consumption was an important factor to decrease gastrointestinal cancers.

Burden of gastrointestinal cancers in China from 1990 to 2019 and projection through 2029

Although gastrointestinal (GI) cancers pose a great challenge to public health, data are scant for understanding the burden of GI cancers in China. We aimed to provide an updated estimate of the burden of major GI cancers in China over three decades. According to the GLOBOCAN 2020 database, 1,922,362 GI cancer cases were newly diagnosed and 1,497,388 deaths occurred in China in 2020, with the highest incidence in colorectal cancer (555,480 new cases; 23.90/100,000 age-standardized incidence rate [ASIR]) and the highest mortality in liver cancer (391,150 deaths; 17.20/100,000 age-standardized mortality rate [ASMR]). The age-standardized rates (ASRs) in incidence, mortality, and disability-adjusted life year (DALY) rates for esophageal, gastric, and liver cancers have declined overall (1990–2019, average annual perventage change [AAPC] < 0%, p < 0.001) but have become flattened or reversed in recent years, alarmingly. The spectrum of GI cancers in China will continue transitioning in the next decade, characterized by rapid increases in colorectal and pancreatic cancers in addition to a high burden of esophageal, gastric, and liver cancers. High body-mass index was found to be the fastest-growing risk factor for GI cancers (estimated annual perventage change [EAPC]: 2.35%–3.20%, all p < 0.001), whereas smoking and alcohol consumption remained the top contributors to GI cancer-related deaths in men. In conclusion, GI cancers in China are challenging the healthcare system with a growing burden and a transitioning pattern. Comprehensive strategies are needed to reach the Healthy China 2030 target.

The Rise of Gastrointestinal Cancers as a Global Phenomenon: Unhealthy Behavior or Progress?

The overall burden of cancer is rapidly increasing worldwide, reflecting not only population growth and aging, but also the prevalence and spread of risk factors. Gastrointestinal (GI) cancers, including stomach, liver, esophageal, pancreatic, and colorectal cancers, represent more than a quarter of all cancers. While smoking and alcohol use are the risk factors most commonly associated with cancer development, a growing consensus also includes dietary habits as relevant risk factors for GI cancers. Current evidence suggests that socioeconomic development results in several lifestyle modifications, including shifts in dietary habits from local traditional diets to less-healthy Western diets. Moreover, recent data indicate that increased production and consumption of processed foods underlies the current pandemics of obesity and related metabolic disorders, which are directly or indirectly associated with the emergence of various chronic noncommunicable conditions and GI cancers. However, environmental changes are not restricted to dietary patterns, and unhealthy behavioral features should be analyzed with a holistic view of lifestyle. In this review, we discussed the epidemiological aspects, gut dysbiosis, and cellular and molecular characteristics of GI cancers and explored the impact of unhealthy behaviors, diet, and physical activity on developing GI cancers in the context of progressive societal changes.

Does Alcohol Affect Gastrointestinal Cancer Risk: A Review Updating the Briefings of Related Factors?

Alcohol consumption is a significant risk factor for gastrointestinal cancers that may be controlled. The risk of cancer increases with the amount and duration of drinking. Even occasional drinking can raise cancer risk; 100 g or less per week is presently thought to be the upper limit for low-risk consumption. Alcohol is causally linked to colorectal cancer, hepatocellular carcinoma, gastric cancer, oesophageal squamous cell cancer, and most likely also pancreatic cancer. Alcohol can have a multiplicative effect on the development of gastrointestinal cancer when paired with tobacco usage or being overweight. The recent rises in the incidence of early-onset gastrointestinal cancers in various Western nations may have been influenced by alcohol use. It is important to encourage those who use alcohol in a harmful way to enroll in cancer screening programmes. Eliminating alcohol consumption seems to be effective in lowering the elevated cancer risk that alcohol causes.

Helicobacter pylori infection as a risk factor for gastrointestinal cancer

Helicobacter pylori infection as a risk factor for gastrointestinal cancer

A link between appendectomy and gastrointestinal cancers: a large-scale population-based cohort study in Korea

An association between appendectomy and subsequent gastrointestinal (GI) cancer development has been postulated, although the evidence is limited and inconsistent. To provide clarification, we investigated the link between appendectomy and GI cancers in a large nationwide appendectomy cohort. This cohort was derived from the claims database of the National Health Insurance Service in South Korea and comprised 158,101 patients who had undergone appendectomy between 2007 and 2014. A comparison cohort of 474,303 subjects without appendectomy was selected after 1:3 matching by age and sex. The incidence of GI cancers after appendectomy was observed, and risk factors for GI cancers were determined by using a multivariable-adjusted proportional hazards model. Appendectomy did not significantly increase the incidence of GI cancers in the overall population (1.529 and 1.557 per 1000 person-years in the non-appendectomy and appendectomy cohorts, respectively). However, appendectomy significantly increased the incidence of GI cancers in subgroups consisting of elderly (≥ 60 years) patients (adjusted HR, 1.102; 95% confidence interval, 1.011–1.201; p = 0.028) or women (adjusted HR, 1.180; 95% confidence interval, 1.066–1.306; p = 0.001).

Mechanisms linking obesity and gastrointestinal cancers

Introduction and purpose: The worldwide prevalence of obesity increased threefold between 1975 and 2016. Obesity is a risk factor for gastrointestinal cancers, including the pancreas, liver, esophagus, colorectum, stomach cardia, and gallbladder. This work is an analysis of the available PubMed literature on relationship between obesity and gastrointestinal cancers and possible mechanisms linking them.Brief description of the state of knowledge: There is a number of mechanisms responsible for obesity associated gastrointestinal cancers. Excess adiposity leads to: metabolic syndrome, chronic inflammation, altered production of steroid hormones and adipokines as well as changes in insulin and IGF1 signaling. This study examines the processes leading to obesity-associated colorectal, esophageal, gastric, and pancreatic cancers, which are known to be the most prevalent and lethal cancers worldwide. In this review, the mechanisms of gastrointestinal cancerogenesis such as changes in insulin and insulin-like growth factor signaling pathways, chronic inflammation associated to obesity, altered adipokine and inflammatory factors levels, are being discussed.Conclusions: Thorough understanding of the biological processes connecting obesity, metabolic health and gastrointestinal cancers may help to discover new risk factors and biomarkers, improve preventive strategies and invent ground-breaking treatment.Key words: obesity; gastrointestinal cancers; mechanisms of carcinogenesis.

Detection of the periodontal pathogen Porphyromonas Gingivalis in Oral Squamous Cell Carcinoma

Background: The concept of infection-based carcinogenesis is gaining an increasing attention. Also periodontitis has been extensively studied as possible risk factor for gastrointestinal cancers including oral cancer. Methodology: Using conventional PCR, we detected the presence of the key periodontal pathogen Porphyromonas gingivalis (P. gingivalis) in 25 oral cancer fresh tissue specimens versus 25 healthy oral mucosal tissue.. Results: P. gingivalis showed significantly higher prevalence in control group with slightly higher loads in cancer tissue. Bacterial presence was not found to be correlated with tumor progression. Conclusion: P. gingivalis was not found to play a possible role in the cancerous lesion. More studies should be implemented to investigate the bacterial involvement in the oral tumors.

Mechanisms of resveratrol in the prevention and treatment of gastrointestinal cancer.

Gastrointestinal (GI) cancer is one of the leading causes of cancer-related deaths worldwide. According to the Global Cancer Statistics, colorectal cancer is the second leading cause of cancer-related mortality, closely followed by gastric cancer (GC). Environmental, dietary, and lifestyle factors including cigarette smoking, alcohol intake, and genetics are the most important risk factors for GI cancer. Furthermore, infections caused by Helicobacter pylori are a major cause of GC initiation. Despite improvements in conventional therapies, including surgery, chemotherapy, and radiotherapy, the length or quality of life of patients with advanced GI cancer is still poor because of delayed diagnosis, recurrence and side effect. Resveratrol (3, 4, 5-trihydroxy-trans-stilbene; Res), a natural polyphenolic compound, reportedly has various pharmacologic functions including anti-oxidant, anti-inflammatory, anti-cancer, and cardioprotective functions. Many studies have demonstrated that Res also exerts a chemopreventive effect on GI cancer. Research investigating the anti-cancer mechanism of Res for the prevention and treatment of GI cancer has implicated multiple pathways including oxidative stress, cell proliferation, and apoptosis. Therefore, this paper provides a review of the function and molecular mechanisms of Res in the prevention and treatment of GI cancer.

SREBPs in the control of intestinal homeostasis and tumorigenesis

Lipids are key regulators of the growth and differentiation of intestinal epithelial cells, including intestinal stem cells (ISC). High‐fat diets and obesity are serious risk factors for gastrointestinal cancers in humans. Sterol regulatory element‐binding proteins (SREBPs) are transcription factors that control lipid synthesis and uptake in the intestine. Our recent studies have shown that SREBPs and their major products, sterols (from SREBP‐2) and unsaturated fatty acids (from SREBP‐1) have a critical role in sustaining growth of the intestinal epithelia: (1) The loss of Scap, which controls intracellular cleavage events required for SREBP activation, reduces lipid synthesis and causes a lethal intestinal injury in mice characterized by a loss of intestinal crypts, which house ISCs. (2) When SREBP‐2 is inactivated in intestinal epithelium, hyperplasia of intestinal crypts and hypertrophy of the intestine results. In SREBP‐2 knockouts, sterol synthesis falls while unsaturated fatty acid synthesis does not, owing to an increase in SREBP‐1. (3) Despite this overgrowth phenotype, ablation of SREBP‐2 in intestinal epithelia of mice blocks the formation of adenomas caused by mutant APC. These findings indicate that SREBPs govern intestinal epithelial homeostasis in complex ways. We propose that SREBPs maintain homeostasis of intestinal epithelia by producing specific, yet‐to‐be identified lipid metabolites that sustain the proliferation of ISCs. These pathways control intestinal organ size and malignant potential, which bears on human diseases of under‐ or over‐proliferation of the intestine, such as short gut syndrome and colorectal cancer, the 3rd most common cause of cancer death in the U.S.Support or Funding InformationNIH‐R01DK121842, NIH‐K08DK102652

Dextran sulfate sodium mouse model of inflammatory bowel disease evaluated for systemic genotoxicity via blood micronucleus and Pig-a gene mutation assays

Inflammatory bowel disease (IBD) is an important risk factor for gastrointestinal cancers. Inflammation and other carcinogenesis-related effects at distal, tissue-specific sites require further study. In order to better understand if systemic genotoxicity is associated with IBD, we exposed mice to dextran sulfate sodium salt (DSS) and measured the incidence of micronucleated cells (MN) and Pig-a mutant phenotype cells in blood erythrocyte populations. In one study, 8-week-old male CD-1 mice were exposed to 0, 1, 2, 3 or 4% w/v DSS in drinking water. The 4-week in-life period was divided into four 1-week intervals-alternately on then off DSS treatment. Low volume blood samples were collected for MN analysis at the end of each week, and cardiac blood samples were collected at the end of the 4-week period for Pig-a analyses. The two highest doses of DSS were observed to induce significant increases in reticulocyte frequencies. Even so, no statistically significant treatment-related effects on the genotoxicity biomarkers were evident. While one high-dose mouse showed modestly elevated MN frequencies during the DSS treatment cycles, it also exhibited exceptionally high reticulocyte frequencies (e.g. 18.7% at the end of the second DSS cycle). In a second study, mice were treated with 0 or 4% DSS for 9-18 consecutive days. Exposure was continued until rectal bleeding or morbidity was evident, at which point the treatment was terminated and blood was collected for MN analysis. The Pig-a assay was conducted on samples collected 29 days after the start of treatment. The initial blood specimens showed highly elevated reticulocyte frequencies in DSS-exposed mice (mean ± SEM = 1.75 ± 0.10% vs. 13.04 ± 3.66% for 0 vs. 4% mice, respectively). Statistical analyses showed no treatment-related effect on MN or Pig-a mutant frequencies. Even so, the incidence of MN versus reticulocytes in the DSS-exposed mice were positively correlated (linear fit R2 = 0.657, P = 0.0044). Collectively, these results suggest that in the case of the DSS CD-1 mouse model, systemic effects include stress erythropoiesis but not remarkable genotoxicity. To the extent MN may have been slightly elevated in a minority of individual mice, these effects appear to be secondary, likely attributable to stimulated erythropoiesis.

Prevalence and Risk Factors of Gastric and Colorectal Cancer after Cholecystectomy.

BackgroundPrevious studies on the relationship between gastrointestinal (GI) cancer and cholecystectomy remain inconclusive. We aimed to evaluate this relationship, albeit particularly between cholecystectomy and gastric cancer or colorectal cancer (CRC), and the risk factors of cancer among individuals who have undergone cholecystectomy in Korea.MethodsIn total, 4,222 patients who underwent laparoscopic or open cholecystectomy at our institution between January 2006 and December 2013 were included. Patients who underwent cholecystectomy for gallbladder cancer or were undergoing surgery for GI, hepatic, or pancreatobiliary cancers were excluded, as were those who developed stomach cancer or CRC within a year of their cholecystectomy. The included patients were followed until July 20, 2020. The standardized incidence ratio (SIR) was used to calculate the relative risk of GI cancer in cholecystectomy patients.ResultsThe median patient age (n = 3,588) at the time of cholecystectomy was 54.0 (range, 19–95) years, and the male-to-female ratio was 1:1.04. The median follow-up period after cholecystectomy was 15.0 (range, 0–146) months. We found a 108% greater risk of CRC (SIR, 2.08; 95% confidence interval [CI], 1.28–3.17) and 154% increased risk of CRC in females (SIR, 2.54; 95% CI, 1.16–4.84). Based on multivariate analysis, an age of > 60 years was a significant risk factor for GI cancer in cholecystectomy patients.ConclusionCholecystectomy may increase risk of CRC, especially in females. Age was considered a risk factor of GI cancers in patients with history of cholecystectomy.

Is periodontitis a risk indicator for gastrointestinal cancers? A meta-analysis of cohort studies.

To evaluate the association between periodontitis and the incidence and mortality of gastrointestinal cancer. A comprehensive literature search was conducted to identify all relevant studies published prior to April 2019 according to the established inclusion criteria. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with a random-effects model. We identified 10 studies with 26 estimates of the relationship between periodontitis and gastrointestinal cancer. The HR for the incidence of gastrointestinal cancer in periodontitis was 1.23 (95% CI: 1.10-1.37). Subgroup analyses showed that periodontitis was associated with an increased risk of gastrointestinal cancers in prospective cohort studies and high-quality studies, North American individuals, and individuals 18years or older, as well as when the dental status was self-reported and when the study was adjusted for smoking. A meta-analysis of nine reports demonstrated that periodontitis was associated with increased mortality from gastrointestinal cancer (HR=1.59, 95% CI: 1.16-2.16). Additionally, periodontitis was associated with mortality from pancreatic cancer (HR=2.20, 95% CI: 1.44-3.37); thus, periodontitis may be a risk factor for pancreatic cancer. Our meta-analysis demonstrated that periodontitis may be a risk factor for gastrointestinal cancers. Additional prospective cohort studies are warranted to confirm these findings.

Obesity and gastrointestinal cancers - where do we go from here?

Obesity is an established risk factor for gastrointestinal cancers. Interventions that reduce the burden of obesity at both the societal and individual level and targeted interventions among those at higher risk of cancer should be developed, supported by advances in understanding of the biology that underpins the obesity–cancer link.

Abstract B39: Understanding the association of gut microbiota and tumor microenvironment in gastric and esophageal cancer

Abstract Gastric and esophageal cancers remain the second and the sixth leading cause of cancer related deaths respectively. Dysbiosis of the gut microbiome remains a strong risk factor for gastrointestinal cancer, likely related to altered mucosal immunity and a pro-inflammatory immune microenvironment. However, the molecular interactions between host human cells and the microbiome are poorly understood as it pertains to gastric and esophageal cancer. Our main goal is to understand how alteration of regional mucosal microbiome alters the tumor microenvironment, thus creating conditions conducive to tumorigenesis. Understanding these changes at the molecular level will help contribute to our knowledge of the disease pathophysiology. Using a novel customized computational pipeline to identify and characterize bacteria from low microbial content endoscopic samples (Zhang et al., Genome Biol 2015), we used low-pass (10-30x) whole genome sequencing (WGS) to examine the microbiome composition of 15 gastric cancer samples along with their adjacent non-cancer mucosal tissue (n=30). We found a higher overall bacterial content in tumor samples compared to that of their corresponding matching normal tissues. Furthermore, we observed a dysbiosis in samples positive for Helicobacter pylori, consistent with previous findings that H. pylori alters composition of the gastric microbiome. Although a wide variety of other microbes were detected, we found specific enrichment of organisms like Veilonella Parvula (12/15) and Prevotella melaninogenica (10/15) in tumor tissues, both of which have been implicated in tumorigenicity. A subset of these samples (10 gastric cancer and 12 adjacent normal) underwent parallel RNAseq analysis and using a gene expression signature panel of 176 genes compiled from several published series, we examined immune cell types, specifically B cells, CD8+ T cells, Treg cells, CD4+ Th1, Th2 and Th17 helper cells and macrophages, to determine an association with tumor versus the normal mucosa. We found an overall higher immune response, and more specifically a higher association of Th1 and Th2 helper cells as well as macrophages, with tumors as compared to normal mucosa. We further corroborated these findings using a single cell RNA sequencing approach on three tumor and matching normal samples. Using ELISA, we detected a significantly increased expression of pro-inflammatory cytokines such as TNFα, IL-8, GRO, MCP-1 and IL-1a in tumor samples than in normal mucosa. Increased expression of TNF-α and IL-8 has been directly correlated to tumor invasion and metastasis, and tumor vascularity respectively. Additionally, MCP-1 has been shown to be important in recruitment of macrophages and is secreted by gastric epithelial cells in response to pro-inflammatory cytokines upon H. pylori infection. We used a similar approach, of performing WGS and RNAseq analysis in parallel, on 9 normal squamous cell carcinoma, 8 non-dysplastic Barrett’s esophagus and 6 esophageal adenocarcinoma samples (n = 23 samples). WGS analysis revealed a higher microbial diversity in normal squamous cell carcinomas compared to the non-dysplastic Barrett’s esophagus with high abundance of Veilonella Parvula, Prevotella melaninogenica and Streptococcus parasanguinis. Unsupervised clustering analysis of the entire data set revealed high abundance of Fusobacterium nucleatum in adenocarcinoma samples, which has been associated with a shorter survival in Esophageal cancer. Unsupervised clustering analysis of RNAseq results revealed a high enrichment of CD4+ Th1 and Th2 helper cell as well as CD8+ T cell associated immune response in some adenocarcinoma and non-dysplastic Barrett’s esophageal samples. Together, our data are derived from endoscopic biopsy samples from patients, and suggest that both gastric and esophageal cancers display distinct microbial patterns associated with chronic inflammation and a tumor-promoting pro-inflammatory microenvironment. Citation Format: Prashant V. Thakkar, Chao Zhang, Prateek Sharma, Sreekar Vennelaganti, Doron Betel, Manish A. Shah. Understanding the association of gut microbiota and tumor microenvironment in gastric and esophageal cancer [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr B39.

Abstract 5128: Understanding the association of gut microbiota and tumor microenvironment in gastric and esophageal cancer

Abstract Gastric and Esophageal cancers remain one of the leading causes of cancer related deaths. Dysbiosis of gut microbiome is a strong risk factor for gastrointestinal cancer, likely due to altered mucosal immunity and pro-inflammatory immune microenvironment. However, molecular interactions between host human cells and microbiome are poorly understood in context of gastric and esophageal cancer. Our main goal is to understand how altered mucosal microbiome alters tumor microenvironment, thus creating conditions conducive to tumorigenesis. Using a novel computational pipeline combined with low-pass (10-30x) whole genome sequencing (WGS), we examined microbiome composition of 15 gastric cancer (GC) and adjacent normal tissue (n=30). We found a higher overall bacterial content in tumor samples compared to that of matching normal tissues. Furthermore, we observed dysbiosis in H. pylori positive samples, consistent with previous findings. Among other microbes, we found specific enrichment of V. Parvula (12/15) and P. melaninogenica (10/15) in tumor tissues, both of which have been implicated in tumorigenicity. A subset of these samples (10 GC and 12 normal) underwent parallel RNAseq analysis. Using gene expression signature panel of 176 genes, we examined association of various immune cell types with tumor versus normal mucosa. We found an overall higher immune response, and higher association of Th1 and Th2 helper cells and macrophages, with tumors as compared to normal mucosa. We further corroborated these findings using single cell RNAseq approach. Using ELISA, we detected significantly increased expression of pro-inflammatory cytokines such as TNF-α, IL-8, GRO, MCP-1 and IL-1a in tumor samples than normal mucosa. Increased TNF-α and IL-8 expression has been directly correlated to tumor invasion and metastasis, and tumor vascularity respectively. Additionally, MCP-1 is known to recruit macrophages and is secreted by gastric epithelial cells in response to pro-inflammatory cytokines upon H. pylori infection. Using a similar approach, we performed WGS and RNAseq, on 9 normal squamous cell carcinoma (NSCC), 8 non-dysplastic Barrett's esophagus (BE) and 6 esophageal adenocarcinoma samples. WGS analysis revealed higher microbial diversity in NSCCs compared to BE samples with high abundance of V. Parvula, P. melaninogenica and S. parasanguinis. Unsupervised clustering analysis revealed high abundance of F. nucleatum in adenocarcinoma, which has been associated with shorter survival in esophageal cancer. Unsupervised clustering analysis of RNAseq data revealed high enrichment of CD4+ Th1 and Th2 helper cell and CD8+ T cell associated immune response in some adenocarcinoma and BE samples. Together our data suggest that both gastric and esophageal cancers display distinct microbial patterns associated with chronic inflammation and tumor-promoting pro-inflammatory microenvironment. Citation Format: Prashant V. Thakkar, Chao Zhang, Prateek Sharma, Sreekar Vennelaganti, Doron Betel, Manish A. Shah. Understanding the association of gut microbiota and tumor microenvironment in gastric and esophageal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5128.

Role of prostanoids in gastrointestinal cancer.

Chronic inflammation is a risk factor for gastrointestinal cancer and other diseases. Most studies have focused on cytokines and chemokines as mediators connecting chronic inflammation to cancer, whereas the involvement of lipid mediators, including prostanoids, has not been extensively investigated. Prostanoids are among the earliest signaling molecules released in response to inflammation. Multiple lines of evidence suggest that prostanoids are involved in gastrointestinal cancer. In this Review, we discuss how prostanoids impact gastrointestinal cancer development. In particular, we highlight recent advances in our understanding of how prostaglandin E2 induces the immunosuppressive microenvironment in gastrointestinal cancers.

Connecting gastrointestinal cancer risk to cadmium and lead exposure in the Chaoshan population of Southeast China

Cadmium (Cd) and lead (Pb) pose a serious threat to human health because of its carcinogenicity. China ranks first according to the Global Cancer Report for 2014 in newly diagnosed gastrointestinal cancers and cancer deaths. The aim of the present study was to evaluate the association of Cd and Pb burden with the risk of gastrointestinal cancers in a hospital-based case-control study from southern regions of China, Chaoshan area. A total of 279 hospitalized patients were recruited in this study, of which 167 were gastrointestinal cancer cases (70 esophageal cancer, 51 gastric cancer, and 46 colorectal cancer), and 112 controls were recruited from two hospitals in the Chaoshan area of southeast China. Basic clinical data and information on gender, age, and other demographic characteristics were collected from medical records. Blood Cd and Pb levels were detected by graphite furnace atomizer absorption spectrophotometry (GFAAS). Blood Cd/Pb levels and over-limit ratios between cases and controls were compared by Mann-Whitney U and Kruskal-Wallis H tests. We used logistic regression to estimate odds ratios (ORs) as measures of relative risk and explored the relationships between blood Cd/Pb levels and gastrointestinal cancer risk and clinicopathological characteristics. Median levels of blood Cd and Pb in cases (2.12 and 60.03μg/L, respectively) were significantly higher than those of controls (1.47 and 53.84μg/L, respectively). The over-limit ratios for Cd (≥ 5μg/L) and Pb (≥ 100μg/L) in the cases were both higher than that of controls. Blood Cd levels had a tendency to accumulate in the human body with gender, age, and tobacco smoking, while blood Pb levels only were associated with tobacco smoking. The logistic regression model illustrated that gastrointestinal cancers were significantly associated with blood Cd levels and blood Pb levels. The concentrations of Cd and Pb in patients with T3 + T4 stage were markedly higher than in patients with T1 + T2. On the other hand, blood Cd levels were dramatically increased in the distant -metastasis (M1). Blood Cd and Pb levels are significantly higher in gastrointestinal cancers compared to controls. Cd and Pb appear to be risk factors for gastrointestinal cancers in Chaoshan region, and higher levels of Cd and Pb may promote the occurrence and progression of gastrointestinal cancers.

Author Correction: Opium Consumption and the Incidence of Cancer: Does Opium Account as an Emerging Risk Factor for Gastrointestinal Cancer?

The original version of this article unfortunately contained a mistake in the author group section. The correct name of the fourth author is "Reza Shirkoohi."The original article has been corrected.