Development Of Gastrointestinal Cancers Research Articles

Investigating the Influence of Gut Microbiota-related Metabolites in Gastrointestinal Cancer.

Gastrointestinal (GI) cancer is a major health concern due to its prevalence, impact on well-being, high mortality rate, economic burden, and potential for prevention and early detection. GI cancer research has made remarkable strides in understanding biology, risk factors, and treatment options. An emerging area of research is the gut microbiome's role in GI cancer development and treatment response. The gut microbiome, vital for digestion, metabolism, and immune function, is increasingly linked to GI cancers. Dysbiosis and alterations in gut microbe composition may contribute to cancer development. Scientists study how specific bacteria or microbial metabolites influence cancer progression and treatment response. Modulating the gut microbiota shows promise in enhancing treatment efficacy and preventing GI cancers. Gut microbiota dysbiosis can impact GI cancer through inflammation, metabolite production, genotoxicity, and immune modulation. Microbes produce metabolites like short-chain fatty acids, bile acids, and secondary metabolites. These affect host cells, influencing processes like cell proliferation, apoptosis, DNA damage, and immune regulation, all implicated in cancer development. This review explores the latest research on gut microbiota metabolites and their molecular mechanisms in GI cancers. The hope is that this attempt will help in conducting other relevant research to unravel the precise mechanism involved, identify microbial signatures associated with GI cancer, and develop targets.

A prognostic model established using bile acid genes to predict the immunity and survival of patients with gastrointestinal cancer.

The metabolism of abnormal bile acids (BAs) is implicated in the initiation and development of gastrointestinal (GI) cancer. However, there was a lack of research on the molecular mechanisms of BAs metabolism in GI. Genes involved in BAs metabolism were excavated from public databases of The Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) database, and Molecular Signatures Database (MSigDB). ConsensusClusterPlus was used to classify molecular subtypes for GI. To develop a RiskScore model for predicting GI prognosis, univariate Cox analysis was performed on the genes in protein-protein interaction (PPI) network, followed by using Lasso regression and stepwise regression to refine the model and to determine the key prognostic genes. Tumor immune microenvironment in GI patients from different risk groups was assessed using the ESTIMATE algorithm and enrichment analysis. Reverse transcription-quantitative real-time PCR (RT-qPCR), Transwell assay, and wound healing assay were carried out to validate the expression and functions of the model genes. This study defined three molecular subtypes (C1, C2, and C3). Specifically, C1 had the best prognosis, while C3 had the worst prognosis with high immune checkpoint gene expression levels and TIDE scores. We selected nine key genes (AXIN2, ATOH1, CHST13, PNMA2, GYG2, MAGEA3, SNCG, HEYL, and RASSF10) that significantly affected the prognosis of GI and used them to develop a RiskScore model accordingly. Combining the verification results from a nomogram, the prediction of the model was proven to be accurate. The high RiskScore group was significantly enriched in tumor and immune-related pathways. Compared with normal gastric mucosal epithelial cells, the mRNA levels of the nine genes were differential in the gastric cancer cells. Inhibition of PNMA2 suppressed migration and invasion of the cancer cells. We distinguished three GI molecular subtypes with different prognosis based on the genes related to BAs metabolism and developed a RiskScore model, contributing to the diagnosis and treatment of patients with GI.

The Risk of Oral Cancer and the High Consumption of Thermally Processed Meat Containing Mutagenic and Carcinogenic Compounds.

The International Agency for Research on Cancer has classified the consumption of heat-processed meat as a direct human carcinogen and the consumption of red meat as a probable carcinogen. Mutagenic and carcinogenic compounds present in meat dishes include, among others, polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines (HAAs). These compounds can cause the development of gastrointestinal cancer. Oral cancer is one of the world's research priorities due to the ever-increasing incidence rate. However, the effect of diet on oral cancer is still a poorly recognized issue. The aim of this study was to assess the relationship between the risk of oral cancer and dietary ingredients with a particular emphasis on red meat and thermally processed meat. This study was conducted among patients with oral cancer in 2022 and 2023. The shortened standardized Food Frequency Questionnaire (FFQ) and a multivariate regression statistical analysis were used. The high consumption of red meat in general and thermally processed meat, especially smoked, fried, roasted and boiled, increases the risk of oral cavity cancer. Limiting the consumption of meat products and modifying the methods of preparing meat dishes may reduce exposure to carcinogenic compounds from the diet and thus reduce the risk of developing oral cancer.

Association between iron deficiency anemia and subsequent stomach and colorectal cancer diagnosis in Germany

PurposeIron deficiency anemia (IDA) is the most common form of anemia worldwide, resulting in a high burden of disease. Accumulating evidence suggests that IDA is associated with the development of gastrointestinal (GI) cancers.MethodsData from the IDA database (IQVIA) of primary care practices in Germany of adult patients first diagnosed with IDA between January 2005 and December 2021 were retrospectively analyzed and compared with a 1:1 propensity score-adjusted cohort without IDA. Study outcomes were first stomach cancer or colorectal cancer (CRC) diagnosis up to 10 years after the index date as a function of IDA.ResultsA total of 122,502 individuals with IDA and 122,502 individuals without IDA were included. The 10-year cumulative incidence of CRC was 1.4% in the IDA patients compared to 0.8% in the cohort without IDA (p < 0.001). Regression analysis revealed a significant association between IDA and subsequent CRC (HR 2.05; 95% CI 1.83–2.30). Stomach cancer was diagnosed in 0.3% of IDA patients compared to 0.2% in the non-IDA cohort during the 10-year follow-up period (p = 0.002). However, this was significant only in the age group > 80 years (HR 2.73; 95% CI 1.60–4.67) and in men (HR 1.90; 95% CI 1.38–2.61).ConclusionThese findings add to the literature and suggest an association between IDA and GI cancers. The extent to which this association is due to GI bleeding or other pathophysiological processes that may be caused by IDA requires further investigation, particularly experimental studies.

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.

The Potential Therapeutic Applications of CRISPR/Cas9 in the Treatment of Gastrointestinal Cancers.

Gastrointestinal (GI) cancer is one the most prevalent types of cancer. Despite current chemotherapy's success, patients with GI cancer continue to have a dismal outcome. The onset and progression of cancer are caused by alterations and the abnormal expression of several families of genes, like tumor-suppressor genes, oncogenes, and chemotherapy-resistant genes. The final purpose of tumor therapy is to inhibit cellular development by modifying mutations and editing the irregular expression of genes It has been reported that CDH1, TP53, KRAS, ARID1A, PTEN, and HLA-B are the commonly mutated genes in GI cancer. Gene editing has become one potential approach for cases with advanced or recurrent CRC, who are nonresponsive to conventional treatments and a variety of driver mutations along with progression cause GI progression. CRISPR/Cas9 technique is a reliable tool to edit the genome and understand the functions of mutations driving GI cancer development. CRISPR/Cas9 can be applied to genome therapy for GI cancers, particularly with reference to molecular-targeted medicines and suppressors. Moreover, it can be used as a therapeutic approach by knocking in/out multiple genes. The use of CRISPR/ Cas9 gene editing method for GI cancer therapy has therefore resulted in some improvements. There are several research works on the role of CRISPR/Cas9 in cancer treatment that are summarized in the following separate sections. Here, the use of CRISPR/Cas9-based genome editing in GI and the use of CRISPR/Cas9 is discussed in terms of Targeting Chemotherapy Resistance-related Genes like; KRAS, TP53, PTEN, and ARID1A.

A rapid and sensitive CRISPR-Cas12a for the detection of Fusobacterium nucleatum.

Fusobacterium nucleatum (Fn), as a conditional pathogen, can cause a range of oral and gastrointestinal diseases. However, existing clinical detection methods require expensive equipment and complex procedures, which are inconvenient for large-scale screening in epidemiological research. The purpose of this study was to establish a reliable, rapid, and inexpensive detection method based on CRISPR/Cas12a technology for the detection of Fn. Specific recombinase polymerase amplification (RPA) primer sequences and crRNA sequences were designed based on the nusG gene of Fn. Subsequently, a fluorescence assay and a lateral flow immunoassay were established using the RPA and CRISPR-Cas12a system (RPA-CRISPR-Cas12a). Sensitivity validation revealed a limit of detection of 5 copies/µL. This method could distinguish Fn from other pathogens with excellent specificity. Furthermore, the RPA-CRISPR-Cas12a assay was highly consistent with the classical quantitative real-time PCR method when testing periodontal pocket samples. This makes it a promising method for the detection of Fn and has the potential to play an increasingly important role in infectious disease testing.IMPORTANCEFusobacterium nucleatum (Fn) naturally exists in the microbial communities of the oral and gastrointestinal tracts of healthy individuals and can cause inflammatory diseases in the oral and gastrointestinal tracts. Recent studies have shown that Fn is closely associated with the occurrence and development of gastrointestinal cancer. Therefore, the detection of Fn is very important. Unlike the existing clinical detection methods, this study established a fluorescence-based assay and lateral flow immunoassay based on the RPA and CRISPR-Cas12a system (RPA-CRISPR-Cas12a), which is fast, reliable, and inexpensive and can complete the detection within 30-40 minutes. This makes it a promising method for the detection of Fn and has the potential to play an increasingly important role in infectious disease testing.

Microbial gene expression analysis of healthy and cancerous esophagus uncovers bacterial biomarkers of clinical outcomes

Local microbiome shifts are implicated in the development and progression of gastrointestinal cancers, and in particular, esophageal carcinoma (ESCA), which is among the most aggressive malignancies. Short-read RNA sequencing (RNAseq) is currently the leading technology to study gene expression changes in cancer. However, using RNAseq to study microbial gene expression is challenging. Here, we establish a new tool to efficiently detect viral and bacterial expression in human tissues through RNAseq. This approach employs a neural network to predict reads of likely microbial origin, which are targeted for assembly into longer contigs, improving identification of microbial species and genes. This approach is applied to perform a systematic comparison of bacterial expression in ESCA and healthy esophagi. We uncover bacterial genera that are over or underabundant in ESCA vs healthy esophagi both before and after correction for possible covariates, including patient metadata. However, we find that bacterial taxonomies are not significantly associated with clinical outcomes. Strikingly, in contrast, dozens of microbial proteins were significantly associated with poor patient outcomes and in particular, proteins that perform mitochondrial functions and iron-sulfur coordination. We further demonstrate associations between these microbial proteins and dysregulated host pathways in ESCA patients. Overall, these results suggest possible influences of bacteria on the development of ESCA and uncover new prognostic biomarkers based on microbial genes. In addition, this study provides a framework for the analysis of other human malignancies whose development may be driven by pathogens.

Criteria and Non-Criteria Antiphospholipid Antibodies and Cancer in Patients with Involuntary Weight Loss.

Cancer patients have higher prevalences of antiphospholipid antibodies (aPLs), occasionally associated with thrombotic events. A cross-sectional study regarding the presence of criteria (IgG/IgM anti-cardiolipin-aCL, anti-β2 glycoprotein I-aβ2GPI) and non-criteria (IgG/IgM anti-phosphatidylserine-aPS, anti-phosphatidylethanolamine-aPE, anti-prothrombin-aPT) aPLs in 146 patients with involuntary weight loss was performed. None of the patients had thrombotic events during the study. Out of the 36 cancer patients, 33 had non-hematologic malignancies. In the cancer subgroup, 60% of the patients had at least one positive aPL, with significantly more patients being positive for aβ2GPI IgG compared with the non-cancer subgroup-p = 0.03, OR = 2.23 (1.02-4.88). When evaluating the titres, aCL IgG/IgM, aβ2GPI IgG, aPE IgG, and aPS IgG had significantly higher values in cancer patients, the best cancer predictor being aβ2GPI IgG-AUC 0.642 (0.542-0.742). Gastrointestinal cancer patients were studied separately, and aCL IgM positivity was significantly higher-p = 0.008, OR = 6.69 (1.35-33.02). Both the titres of aCL IgM (p = 0.006) and aPS IgM (p = 0.03) were higher in the gastrointestinal cancer subgroup, with aCL IgM being the best predictor for gastrointestinal cancer development-AUC 0.808 (0.685-0.932). Despite criteria and non-criteria aPLs being frequent in cancer, their connection with thrombosis in these patients is probably dependent on other important risk factors and needs further research.

Herpes zoster is not associated with subsequent gastrointestinal cancer: data from over 200,000 outpatients in Germany

PurposeGastrointestinal (GI) cancers are an increasing global health challenge. Viral diseases play an important role in the development of GI cancers. For example, Epstein-Barr virus, which belongs to the human herpesvirus family, is a well-recognized risk factor for the development of gastric cancer. The purpose of this study was to investigate a possible association between varicella-zoster virus reactivation and subsequent diagnosis of GI cancer.MethodsIn this retrospective cohort study, a total of 103,123 patients with a first diagnosis of herpes zoster (HZ) between 2005 and 2021 were propensity score matched to a cohort of 103,123 patients without HZ. Patient data was extracted from the Disease Analyzer database (IQVIA). The incidence of GI cancer was compared as a function of HZ. Cox regression analysis was used to examine the association between HZ and GI cancer.ResultsOver a follow-up period of up to 10 years, the incidence of GI cancer did not differ between the two cohorts (HZ cohort 2.26 cases per 1000 patient-years vs. non-HZ cohort 2.37 cases per 1000 patient-years, p = 0.548). In regression analysis, HZ was not associated with an increased risk of developing GI cancer (HR: 0.97; 95% CI 0.89–1.05). Furthermore, no significant effect of the presence of HZ on the incidence of different GI cancer entities was found.ConclusionIn this retrospective cohort study consisting of well-matched patients, we observed no significant association between a HZ infection and the development of GI cancer during a long-term follow-up.

Diet Quality and Subsequent Incidence of Upper Gastrointestinal Cancers: Results from the Golestan Cohort Study.

Recent evidence suggests overall diet quality, as assessed by dietary scores, may play a role in the development of upper gastrointestinal (UGI) cancers. However, the existing dietary scores are derived from high-income countries with different dietary habits than regions with the highest burden of UGI cancers, where limited data is available. This study aimed to investigate the association between overall diet quality and risk of esophageal and stomach cancers in a high-risk region for UGI cancers. We recruited 50045 individuals aged 40-75 between 2004-2008 from northeastern Iran and followed them annually through July 2020. Data on demographics, diet, and various exposures were collected using validated questionnaires. Diet quality was assessed by calculating the Healthy Eating Index (HEI), Alternative Healthy Eating Index (AHEI), Alternative Mediterranean Diet (AMED), Dietary Approaches to Stop Hypertension (DASH), and World Cancer Research Fund-American Institute for Cancer Research (WCRF-AICR) scores. During an average 12 years of follow-up, 359 participants developed esophageal cancer and 358 developed stomach cancer. After adjustments, each standard deviation increase in baseline dietary scores was associated with up to 12% reduction in esophageal cancer risk and up to 17% reduction in stomach cancer risk. Esophageal cancer showed stronger inverse associations with adherence to AMED (HRQ4-vs-Q1=0.69 (0.49-0.98), P-trend=0.038). Stomach cancer showed stronger inverse correlation with WCRF-AICR (HRQ4-vs-Q1=0.58 (0.41-0.83), P-trend=0.004), and DASH (HRC4-vs-C1=0.72 (0.54-0.96), P-trend=0.041). These associations were comparable across different population subgroups. We did not observe significant associations between HEI and AHEI scores and UGI cancers in this population. Despite the differences in consuming individual food groups, adherence to the available dietary recommendations (derived from high-income countries) was associated with lower risk for subsequent esophageal and gastric cancers in this high-risk population. Educating the public to have a healthy eating pattern might be an effective strategy towards prevention of UGI cancers in high-risk regions.

Time-restricted eating for chronodisruption-related chronic diseases.

The circadian timing system enables organisms to adapt their physiology and behavior to the cyclic environmental changes including light-dark cycle or food availability. Misalignment between the endogenous circadian rhythms and external cues is known as chronodisruption and is closely associated with the development of metabolic and gastrointestinal disorders, cardiovascular diseases, and cancer. Time-restricted eating (TRE, in human) is an emerging dietary approach for weight management. Recent studies have shown that TRE or time-restricted feeding (TRF, when referring to animals) has several beneficial health effects, which, however, are not limited to weight management. This review summarizes the effects of TRE/TRF on regulating energy metabolism, gut microbiota and homeostasis, development of cardiovascular diseases and cancer. Furthermore, we will address the role of circadian clocks in TRE/TRF and propose ways to optimize TRE as a dietary strategy to obtain maximal health benefits.

Effects of ranitidine and nizatidine on the risk of gastrointestinal cancer.

Gastrointestinal (GI) cancer occurs in digestive organs such as the stomach, colon, liver, esophagus, and pancreas. About 83,034 cases occurred in Korea alone in 2020. Dietary factors, alcohol consumption, Helicobacter pylori (H. pylori), and lifestyle factors increase the incidence of diseases such as gastritis, peptic ulcer, pancreatitis, and gastroesophageal reflux disease (GERD), which can develop into GI cancer. However, in 2019, the US Food and Drug Administration announced that the drugs ranitidine and nizatidine, which are used for digestive disorders, contain carcinogens. In this study, we investigated the effects of ranitidine and nizatidine on the development of GI cancer. In this study, using National Health Insurance Service-National Sample Cohort (NHIS-NSC) version 2.5 (updated from 2002 to 2019), subjects who developed GI cancer were enrolled in the case group, and those who were at risk of, but did not develop, cancer were enrolled in the control group. Thereafter, risk-set matching was performed (1:3 ratio) by sex and age at the time of diagnosis of cancer in the case group. Through this procedure, 22,931 cases and 68,793 controls were identified. The associations of ranitidine and/or nizatidine with GI cancer were confirmed by adjusted odds ratios (aORs) and 95% confidence intervals (CIs) calculated through conditional logistic regression analysis. The aORs of ranitidine and/or nizatidine users were lower than those of nonusers in all average prescription days groups (< 30 days/year: aOR [95% CI] = 0.79 [0.75-0.82]; 30-59 days/year: aOR [95% CI] = 0.66 [0.59-0.73]; 60-89 days/year: aOR [95% CI] = 0.69 [0.59-0.81]; ≥ 90 days/year: aOR [95% CI] = 0.69 [0.59-0.79]). Sensitivity analyses were conducted with different lag periods for the onset of GI cancer after drug administration, and these analyses yielded consistent results. Additional analyses were also performed by dividing subjects into groups based on cancer types and CCI scores, and these analyses produced the same results. Our study, using nationwide retrospective cohort data, did not find evidence suggesting that ranitidine and nizatidine increase the risk of GI cancer. In fact, we observed that the incidence of GI cancer was lower in individuals who used the drugs compared to nonusers. These findings suggest a potential beneficial effect of these drugs on cancer risk, likely attributed to their ability to improve digestive function.

Ferroptosis, Necroptosis, and Pyroptosis in Gastrointestinal Cancers: The Chief Culprits of Tumor Progression and Drug Resistance.

In recent years, the incidence of gastrointestinal cancers is increasing, particularly in the younger population. Effective treatment is crucial for improving patients' survival outcomes. Programmed cell death, regulated by various genes, plays a fundamental role in the growth and development of organisms. It is also critical for maintaining tissue and organ homeostasis and takes part in multiple pathological processes. In addition to apoptosis, there are other types of programmed cell death, such as ferroptosis, necroptosis, and pyroptosis, which can induce severe inflammatory responses. Notably, besides apoptosis, ferroptosis, necroptosis, and pyroptosis also contribute to the occurrence and development of gastrointestinal cancers. This review aims to provide a comprehensive summary on the biological roles and molecular mechanisms of ferroptosis, necroptosis, and pyroptosis, as well as their regulators in gastrointestinal cancers and hope to open up new paths for tumor targeted therapy in the near future.

Allergic Diseases and Risk of Malignancy of Gastrointestinal Cancers

The aim of this study was to investigate the effect of allergic diseases, including allergic rhinitis, asthma, and atopic dermatitis, on the development of gastrointestinal (GI) cancers. We analyzed 9,892,633 Korean adults who underwent a medical check-up in the year 2009, and they were followed up until the year 2017. Allergic diseases and cancers were defined using the International Classification of Disease Codes. A Cox proportional hazards model was adapted to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). During a 7.3-year follow-up period, 48,045 patients were diagnosed with cancer. For all-combined allergic diseases, significant inverse associations were observed for cancers of the esophagus, stomach, colorectum, and liver (adjusted hazard ratios (aHRs [95% confidence interval, CI] 0.86 [0.82–0.91], 0.93 [0.91–0.94], 0.95 [0.93–0.96], and 0.90 [0.88–0.92], respectively). The sex-stratified analysis showed that the preventive effect of allergic diseases was persistent in gastric, colorectal, and liver cancers regardless of sex, while the inverse associations with esophageal and pancreatic cancers were observed only in men (aHR [95% CI] 0.84 [0.80–0.89] and 0.96 [0.93–0.99]). Allergic diseases, particularly allergic rhinitis, in adults were significantly associated with a decreased risk of most GI cancers, except for gallbladder and biliary tract cancers.

High-LET-Radiation-Induced Persistent DNA Damage Response Signaling and Gastrointestinal Cancer Development.

Ionizing radiation (IR) dose, dose rate, and linear energy transfer (LET) determine cellular DNA damage quality and quantity. High-LET heavy ions are prevalent in the deep space environment and can deposit a much greater fraction of total energy in a shorter distance within a cell, causing extensive DNA damage relative to the same dose of low-LET photon radiation. Based on the DNA damage tolerance of a cell, cellular responses are initiated for recovery, cell death, senescence, or proliferation, which are determined through a concerted action of signaling networks classified as DNA damage response (DDR) signaling. The IR-induced DDR initiates cell cycle arrest to repair damaged DNA. When DNA damage is beyond the cellular repair capacity, the DDR for cell death is initiated. An alternative DDR-associated anti-proliferative pathway is the onset of cellular senescence with persistent cell cycle arrest, which is primarily a defense mechanism against oncogenesis. Ongoing DNA damage accumulation below the cell death threshold but above the senescence threshold, along with persistent SASP signaling after chronic exposure to space radiation, pose an increased risk of tumorigenesis in the proliferative gastrointestinal (GI) epithelium, where a subset of IR-induced senescent cells can acquire a senescence-associated secretory phenotype (SASP) and potentially drive oncogenic signaling in nearby bystander cells. Moreover, DDR alterations could result in both somatic gene mutations as well as activation of the pro-inflammatory, pro-oncogenic SASP signaling known to accelerate adenoma-to-carcinoma progression during radiation-induced GI cancer development. In this review, we describe the complex interplay between persistent DNA damage, DDR, cellular senescence, and SASP-associated pro-inflammatory oncogenic signaling in the context of GI carcinogenesis.

Exposure to weak opioids and risk of gastrointestinal tract cancers: A series of nested case-control studies.

There is evidence gastrointestinal (GI) motility may play a role in the development of GI cancers. Weak opioids (codeine and dihydrocodeine) decrease GI motility, but their effect on GI cancer risk has not been assessed. We aim to assess the association between weak opioids and cancers of the GI tract. A series of nested case-control studies was conducted using Scottish general practice records from the Primary Care Clinical Informatics Unit Research database. Oesophageal (n = 2432), gastric (n = 1443) and colorectal cancer (n = 8750) cases, diagnosed between 1999 and 2011, were identified and matched with up to five controls. Weak opioid use was identified from prescribing records. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression, adjusting for relevant comorbidities and medication use. There was no association between weak opioids and colorectal cancer (adjusted OR = 0.96, CI 0.90, 1.02, P = 0.15). There was an increased risk of oesophageal (adjusted OR = 1.16, CI 1.04, 1.29, P = 0.01) and gastric cancer (adjusted OR = 1.26, CI 1.10, 1.45, P = 0.001). The associations for oesophageal cancer, but not gastric cancer, were attenuated when weak opioid users were compared with users of another analgesic (adjusted OR = 1.03 CI 0.86, 1.22, P = 0.76 and adjusted OR = 1.29 CI 1.02, 1.64, P = 0.04 respectively). In this large population-based study, there was no consistent evidence of an association between weak opioids and oesophageal or colorectal cancer risk, but a small increased risk of gastric cancer. Further investigation is required to determine whether this association is causal or reflects residual confounding or confounding by indication.

Circulating Sex Hormone Levels and Risk of Gastrointestinal Cancer: Systematic Review and Meta-Analysis of Prospective Studies.

Sex hormones may influence the development of gastrointestinal cancer, but evidence is inconsistent. We systematically searched MEDLINE and Embase databases to identify prospective studies examining associations between prediagnostic circulating levels of sex hormones and risk of five gastrointestinal cancers: esophageal, gastric, liver, pancreatic, and colorectal cancer. Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated using random-effects models. Among 16,879 identified studies, 29 were included (11 cohort, 15 nested case-control, and 3 case-cohort studies). Comparing the highest versus lowest tertiles, levels of most sex hormones were not associated with the studied tumors. Higher levels of sex hormone-binding globulin (SHBG) were associated with increased risk of gastric cancer (OR=1.35; 95%CI, 1.06-1.72), but such associations were restricted in men only (OR=1.43; 95%CI, 1.10-1.85) when stratified by sex. Higher SHBG levels were associated with increased risk of liver cancer (OR=2.07; 95%CI, 1.40-3.06). Higher testosterone levels were associated with increased risk of liver cancer overall (OR=2.10; 95%CI, 1.48-2.96), particularly in men (OR=2.63; 95%CI, 1.65-4.18), Asian populations (OR=3.27; 95%CI, 1.57-6.83) and in hepatitis B surface antigen-positive individuals (OR=3.90; 95%CI, 1.43-10.64). Higher levels of SHBG and testosterone were associated with decreased risk of colorectal cancer in men (OR=0.89; 95%CI, 0.80-0.98 and OR=0.88; 95%CI, 0.80-0.97, respectively) but not in women. Circulating levels of sex hormone-binding globulin and testosterone may influence the risk of gastric, liver, and colorectal cancer. Further clarifying the role of sex hormones in the development of gastrointestinal cancer may unravel future novel targets for prevention and treatment.

Single-nucleotide polymorphism in CYP1A1, CYP1B1, CYP2B6, CYP2C8, and CYP2C9 genes and their association with gastrointestinal cancer: A hospital-based case-control study.

Cytochrome P450 (CYP) comprises a group of phase-I metabolizing enzymes that are important in xenobiotics metabolism. Genetic polymorphism of CYPs has been comprehensively studied for their association with a range of diseases. In this study, we assessed single-nucleotide polymorphism (SNP) of CYP1A, CYP1B, CYP2B, and CYP2C and their role in gastrointestinal (GI) cancer susceptibility in the rural population of Maharashtra. In this hospital-based case-control study, the association of polymorphism of CYP genes was studied by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The study subjects included 200 clinically confirmed GI cancer patients and equal number of healthy controls. Odds ratio (OR) with 95% confidence interval (CI) and P value were evaluated to find out the level of association, where P ≤ 0.005 was considered statistically significant. After the analysis of CYP1A1*2A (rs4646903), CYP1B1*3 (rs1059836), CYP2B6*5 (rs3211371), CYP2C8*2 (rs11572103), CYP2C9*2 (rs1799853), and CYP2C9*3 (rs1057910), we noticed that variant (T) allele of CYP2B6*5 possessed significantly elevated risk (OR = 4.43; 95% CI: 2.20-8.90; P < 0.0001) of GI cancer in studied population. The genotypic distribution of G/C heterozygote allele of CYP1B1*3 (OR = 0.19, 95% CI = 0.12-0.32; P < 0.0001) and homozygous variant C/C allele (OR = 0.24, 95% CI = 0.13-0.45; P < 0.0001) showed a negative association with the development of GI cancer. The findings from this study supported that polymorphism of CYP2B6*5gene may be involved in the development of GI cancer. However, other SNPs of CYP1A, CYP1B, and CYP2C genes did not signify the risk for GI cancer in the studied population of rural Maharashtra.

Intestinal Microbiomes In Gastrointestinal Cancer

The intestinal flora, a crucial system of microorganisms in the human body, is crucial to the immune system, metabolism, and inflammatory response of the body. The intestinal flora is one of them, and as a crucial element of the gastrointestinal microecology, it has a significant impact on the development and spread of gastrointestinal cancer as well as its management. The study of intestinal flora has become more in-depth recently as a result of the quick advancement of high-throughput sequencing technology, and the role of intestinal flora in the development and prognosis of gastrointestinal cancer is becoming increasingly obvious. In this article, the key topics covered include the links between Helicobacter pylori and gastric cancer, as well as the relationship between Fusobacterium and colon cancer, and discusses the mechanism by which intestinal microbes affect the treatment of gastrointestinal cancer. The link between gut microbiota and gastrointestinal cancer was further clarified, and the regulation of gut microbiota was proposed as a new management method for the clinical gastrointestinal cancer treatment.