HypothesisA MODEL FOR GASTRIC CANCER EPIDEMIOLOGY
Abstract
It is postulated that one major subtype of gastric carcinoma ("intestinal type ") is the end-result of a series of mutations and cell transformation begun in the first decade of life. The mutagen could be a nitroso compound synthesised in the upper gastrointestinal tract by the action of nitrite (i.e., from food or saliva) on naturally occurring nitrogen compounds. Under normal conditions these nitroso compounds do not reach the gastric epithelial cell, presumably because their synthesis is inhibited by antioxidants present in food or because of their inability to pass the mucous barrier. The barrier may be overcome by abrasives or irritants such as hard grains, food with high sodium-chloride concentration, or surfactants. Once the first mutation occurs, the glandular gastric epithelium is gradually changed to intestinal-type epithelium, the mucous barrier altered, and the pH elevated. Under these conditions, bacteria proliferate in the gastric cavity and facilitate the conversion of nitrates to nitrites, thereby increasing the nitrite pool and the probability of formation of mutagenic-carcinogenic nitroso compounds. This process of gastric atrophy and intestinal metaplasia goes on for 30 to 50 years until some of the individuals affected have the final mutation or cell transformation which allows the cell to become autonomous and invade other tissues.
References (16)
- O. Jarvi et al.
Acta path. microbiol. scand.
(1951) - P. Lauren
Acta path. microbiol. scand.
(1965) - N. Muñoz et al.
Int. J. Cancer
(1971) - P. Correa et al.
J. natn. Cancer Inst.
(1973) - P. Correa et al.
J. natn. Cancer Inst.
(1970) - P. Correa et al.
Recent Results Cancer Res.
(1975) - W. Haenszel et al.
J. natn. Cancer Inst.
(1972)
Cited by (955)
Gastric and duodenal cancer in individuals with Lynch syndrome: a nationwide cohort study
2024, eClinicalMedicineLynch syndrome increases the risk of gastric cancer (GC) and duodenal cancer (DC), particularly in individuals with MLH1 and MSH2 pathogenic variants (PVs). To provide further insight into whether, and from what age, esophagogastroduodenoscopy (EGD) surveillance may be beneficial, we evaluated the cumulative incidence and tumour characteristics of GC and DC in a large nationwide cohort of Dutch individuals with LS.
For this retrospective nationwide cohort study, clinical data of individuals with LS registered at the Dutch Hereditary Cancer Registry were matched with pathology reports filed by the Dutch Pathology registry. All individuals registered between Jan 1, 1989 and Dec 31, 2021 with proven or putative PVs in one of the mismatch repair genes were included. Cumulative incidences of GC and DC were estimated for high-risk (MLH1, MSH2 and EpCAM) and low-risk (MSH6 and PMS2) PVs using competing risk methodology (Fine and Gray method) with death due to other causes as competing risk.
Among 1002 individuals with high-risk and 765 individuals with low-risk PVs, 29 GCs (1.6%) and 39 DCs (2.2%) were diagnosed. Cumulative incidence of GC and DC under the age of 50 was very low (≤1%) for all individuals. At age 70 and 75, cumulative incidence of GC was 3% [95% CI 1%–5%] and 5% [3%–8%] for high-risk PVs and 1% [0%–2%] and 1% [0%–2%] for low-risk PVs (p = 0.006). For DC, cumulative incidence at age 70 and 75 was 5% [3%–7%] and 6% [3%–8%] in high-risk, 1% [0%–1%] and 2% [0%–4%] in low-risk PVs, respectively (p = 0.01). Primary tumour resection was performed in 62% (18/29) of GCs and 77% (30/39) of DC cases. Early-stage GC, defined as TNM stage I, was found in 32% (9/28) of GCs. Early-stage DC, defined as TNM stage I-IIa, was found in 39% (14/36) of DCs.
Individuals with MLH1, MSH2, and EpCAM PVs have an increased risk of developing GC and DC at the age of 70 years, but this risk is very low before the age of 50 years. The age of onset of surveillance, the yield of GC and DC during EGD surveillance, and its cost-effectiveness should be subject of future studies.
None.
Trends of gastric cancer burdens attributable to risk factors in China from 2000 to 2050
2024, The Lancet Regional Health - Western PacificThe incidence of gastric cancer (GC) decreased in past decades, which was thought largely attributable to risk factors control, yet China still accounts for 44% of global GC burdens. We aimed to estimate changing trajectories of proportions of GC burdens attributable to modifiable risk factors from 2000 to 2050 in China, to inform future targeted preventive strategies.
The incidence and new cases of GC were predicted to 2050 using Bayesian age-period-cohort model based on incidence data by anatomical subsites drawn from 682 cancer registries from National Central Cancer Registry. Population attributable fractions (PAFs) were calculated based on prevalence of risk factors and relative risks with GC. Temporal trends of PAFs were described by sex and categories of risk factors using joinpoint analysis.
We observed declining trends of PAFs of Helicobacter pylori (H. pylori) infection, smoking, pickled vegetable and alcohol consumption, but increasing trends of PAFs of unhealthy body mass index and diabetes for GC in China. The combined PAFs of these risk factors were estimated to decrease by 10.57% from 2000 to 2050 for GC. We estimated there will be 279,707 GC (122,796 cardia gastric cancer [CGC] and 156,911 non-cardia gastric cancer [NCGC]) cases in 2050. Out of these cases, 70.18% of GC cases could be attributable to modifiable risk factors, while H. pylori infection was predicted to be responsible for 40.7% of CGC and 62.1% of NCGC cases in 2050.
More than half of GC remained attributable to modifiable risk factors in China. Continued effective strategies on risk factors control are needed to reduce the burden of this highly life-threatening cancer in future.
Beijing Nova Program (No. Z201100006820069), CAMS Innovation Fund for Medical Sciences (CIFMS, grant No. 2021-I2M-1-023), CAMS Innovation Fund for Medical Sciences (CIFMS, grant No. 2021-I2M-1-010), Talent Incentive Program of Cancer Hospital Chinese Academy of Medical Sciences (Hope Star).
Sijunzi decoction ameliorates gastric precancerous lesions via regulating oxidative phosphorylation based on proteomics and metabolomics
2024, Journal of EthnopharmacologySijunzi decoction (SJZD), a traditional Chinese medicine formula, is commonly used in clinical practice for the treatment of gastric precancerous lesions (GPL). However, the mechanism of gastric protection is not fully understood.
The purpose of this study was to systematically evaluate the efficacy of SJZD in blocking the development of GPL and to reveal the underlying mechanism.
First, we established a rat model of GPL, which was induced by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) combined with an irregular diet and 40% ethanol. The efficacy of SJZD was evaluated based on pathological sections and serum biochemical indices. Then, the pharmacodynamic mechanism of SJZD was revealed by quantitative proteomics based on stable isotope dimethyl labeling. At the same time, the pharmacodynamic mechanism was verified by quantitative metabolomics. In addition, the anti-gastritis effect of SJZD was confirmed by a serum pharmacology method in a cell model, and the functional mechanism was further verified.
We demonstrated that SJZD could block the development of GPL in the animal model. Proteomics and metabolomics revealed that SJZD blocks GPL development by regulating oxidative phosphorylation (OXPHOS). In addition, the serum pharmacology results showed that SJZD-containing serum (SJZD-CS) could inhibit apoptosis in MNNG-induced GES-1 cells. OXPHOS inhibitors could significantly reduce the protective effect of SJZD-CS.
SJZD effectively ameliorates GPL, and proteomics and metabolomics revealed that its protective effects are closely related to OXPHOS.
Gastric cancer screening in Western countries: A call to action
2024, Digestive and Liver DiseaseGastric cancer is a major cause of cancer-related death worldwide, despite the reduction in its incidence. The disease is still burdened with a poor prognosis, particularly in Western countries. The main risk factor is the infection by Helicobacter pylori, classified as a class I carcinogen by the IARC, and It is well-known that primary prevention of gastric cancer can be achieved with the eradication of the infection. Moreover, non-invasive measurement of pepsinogens (PGI and PGI/PGII ratio) allows the identification of patients that should undergo upper gastrointestinal (GI) endoscopy. Gastric non-cardia adenocarcinoma is indeed preceded by a well-defined precancerous process that involves consecutive stages, described for the first time by Correa et al. more than 40 years ago, and patients with advance stages of gastric atrophy/intestinal metaplasia and with dysplastic changes should be followed-up periodically with upper GI endoscopies. Despite these effective screening and surveillance methods, national-level screening campaigns have been adopted only in few countries in eastern Asia (Japan and South Korea). In this review, we describe primary and secondary preventive measures for gastric cancer, discussing the need to introduce screening also in Western countries. Moreover, we propose a simple algorithm for screening that could be easily applied in clinical practice.
A deep learning model based on magnifying endoscopy with narrow-band imaging to evaluate intestinal metaplasia grading and OLGIM staging: A multicenter study
2024, Digestive and Liver DiseasePatients with stage III or IV of operative link for gastric intestinal metaplasia assessment (OLGIM) are at a higher risk of gastric cancer (GC). We aimed to construct a deep learning (DL) model based on magnifying endoscopy with narrow-band imaging (ME-NBI) to evaluate OLGIM staging.
This study included 4473 ME-NBI images obtained from 803 patients at three endoscopy centres. The endoscopic expert marked intestinal metaplasia (IM) regions on endoscopic images of the target biopsy sites. Faster Region-Convolutional Neural Network model was used to grade IM lesions and predict OLGIM staging.
The diagnostic performance of the model for IM grading in internal and external validation sets, as measured by the area under the curve (AUC), was 0.872 and 0.803, respectively. The accuracy of this model in predicting the high-risk stage of OLGIM was 84.0%, which was not statistically different from that of three junior (71.3%, p = 0.148) and three senior endoscopists (75.3%, p = 0.317) specially trained in endoscopic images corresponding to pathological IM grade, but higher than that of three untrained junior endoscopists (64.0%, p = 0.023).
This DL model can assist endoscopists in predicting OLGIM staging using ME-NBI without biopsy, thereby facilitating screening high-risk patients for GC.
An artificial intelligence system for chronic atrophic gastritis diagnosis and risk stratification under white light endoscopy
2024, Digestive and Liver DiseaseThe diagnosis and stratification of gastric atrophy (GA) predict patients’ gastric cancer progression risk and determine endoscopy surveillance interval. We aimed to construct an artificial intelligence (AI) system for GA endoscopic identification and risk stratification based on the Kimura-Takemoto classification.
We constructed the system using two trained models and verified its performance. First, we retrospectively collected 869 images and 119 videos to compare its performance with that of endoscopists in identifying GA. Then, we included original image cases of 102 patients to validate the system for stratifying GA and comparing it with endoscopists with different experiences.
The sensitivity of model 1 was higher than that of endoscopists (92.72% vs. 76.85 %) at image level and also higher than that of experts (94.87% vs. 85.90 %) at video level. The system outperformed experts in stratifying GA (overall accuracy: 81.37 %, 73.04 %, p = 0.045). The accuracy of this system in classifying non-GA, mild GA, moderate GA, and severe GA was 80.00 %, 77.42 %, 83.33 %, and 85.71 %, comparable to that of experts and better than that of seniors and novices.
We established an expert-level system for GA endoscopic identification and risk stratification. It has great potential for endoscopic assessment and surveillance determinations.