Gastric cancer diagnosis and prevention: Detecting precancerous at community level

Abstract

The problem of gastric cancer (GC) prevention remains relevant for a long time. Various methods of population serological screening of atrophic gastritis and precancerous changes in the gastric mucosa have been created at present. Modern endoscopic and morphological methods of verification of the diagnosis of precancerous diseases and changes in the gastric mucosa have been introduced into the practice of gastroenterologists and oncologists. GC risk stratification systems allow the formation of risk groups that require population screening. Practical hints for population serological screening of atrophic gastritis, endoscopic and morphological verification of precancerous changes and diseases of the stomach recommend using it: When developing state programs for the prevention of stomach cancer; when implementing preventive measures for stomach cancer by doctors of all specialties; the authors also offer the possibility of use by anyone over the age of 40, provided that they seek methodological help from their doctor; in the work of health schools in any medical and preventive institutions. The use of an assessment system of certain risk factor signatures with prognostic value would add significant assistance to preventive measures against GC.

Key Words: Prevention; Gastric cancer; Strategy; Atrophic gastritis; Serological screening; Precancerous changes

Core Tip: The authors present a consistent system of population-based serological screening for precancerous diseases and changes in the gastric mucosa as a first-line screening strategy. The use of modern endoscopic and morphological diagnostic methods to verify pre-cancerous pathology of the stomach is recommended as a second line of screening for precancerous condition of the stomach. A detailed description of the markers of these pathological changes is given in the manuscript. Recent advances in research to identify the risk factors for stomach cancer have made it possible to use specific science to predict this deadly disease.

INTRODUCTION

Stomach cancer retains its status as the most common type of cancer worldwide. In 2020, more than a million new cases of stomach cancer were detected. According to expert estimates, 1 out of 13 deaths worldwide is due to stomach cancer. Stomach cancer ranks fifth in morbidity and fourth in mortality worldwide. Stomach cancer in men is twice as common as in women, and is the most commonly diagnosed type of cancer and the leading cause of cancer death in specific countries of South and Central Asia. The incidence of stomach cancer is high in East Asia and Eastern Europe, compared with rates in North America and Northern Europe, where they are usually low and close to those in African regions[1]. Data are presented in Table 1.

Table 1 Age-standardized rates of gastric cancer incidence for a regions in 2020.

Rating number	Region	Age-standardized (W) incidence rate per 100000
		Male	Female
1	Eastern Asia	32.5	13.2
2	Eastern Europe	17.4	7.1
3	South America	12.1	6.0
4	Western Asia	11.4	6.1
5	Southern Europe	10.2	5.0
6	Melanesia	9.9	6.2
7	Micronesia/Polynesia	9.7	5.5
8	Caribbean	9.0	5.0
9	Central America	8.7	6.1
10	Western Europe	8.2	3.8
11	South Central Asia	7.4	3.7
12	South-Eastern Asia	7.3	4.0
13	Australia/New Zealand	6.4	2.8
14	Northern Europe	6.2	3.1
15	Northern America	5.4	3.1
16	Northern Africa	5.4	3.5
17	Eastern Africa	4.9	4.2
18	Western Africa	4.8	3.5
19	Southern Africa	4.7	2.4
20	Middle Africa	4.6	3.8

In 2000, stomach cancer was diagnosed in 880000 people worldwide and became the cause of death in 650000[2]. In the following years, the incidence and mortality from stomach cancer continued to grow steadily; the disease still occupies a leading position[3,4]. The prognosis for the next few years is negative, and a further increase in the incidence of stomach cancer is expected[5]. This state of the problem may indicate a low implementation of modern technologies for screening and diagnosis of gastric cancer (GC), which inevitably affects the effectiveness of preventive and therapeutic measures in this disease.

SCREENING FOR PRECANCEROUS CONDITIONS OF THE STOMACH

Screening strategies for precancerous conditions of the stomach

Targeted prevention of GC should include infection screening and screening of precancerous diseases. Screening strategies of the first line should preferably be non-invasive, inexpensive, allowing large groups of people to be examined, both from risk groups for stomach cancer and also symptomatic patients without established hereditary or acquired risk factors, for example, living in regions with a high incidence of stomach cancer. Then, in a smaller population of individuals with identified high risk, screening strategies of the second line should be performed, including invasive diagnosis of the presence of Helicobacter pylori (H. pylori) and its genetic characteristics, as well as endoscopy with biopsy and subsequent histology-to verify and assess the stage of precancerous changes, on which the prognosis of cancer risk in a particular patient will be based in the future[6].

Detection of H. pylori infection

To verify H. pylori infection, a respiratory urease test with carbon C13 or the determination of the H. pylori antigen in feces is recommended. The serological method for the detection of H. pylori (anti-HP IgG) is recommended when is it necessary to screen for infection in a large population. In populations at high risk of developing GC, screening for H. pylori infection is advisable, starting in childhood, by determining antibodies to H. pylori IgG in blood serum using enzyme immunoassay. Global practical recommendations of the World Gastroenterological Organization " H. pylori " should be applied to H. pylori-positive patients.

Detection of atrophic gastritis

According to current concepts, serological screening for atrophic gastritis should start at the age of 40[7-9]. To date, the most well-known and evidence-based serological markers of the atrophic status of the gastric mucosa are such indicators as: Gastrin-17, pepsinogen-I, pepsinogen-II, pepsinogen-I/pepsinogen-II ratio. It’s crucial to detect only postprandial levels of gastrin-17 because fasting gastrin-17 distorts the results due to functional decrease in the secretory activity of the G cells of the gastric glands. This functional decrease in G-cell secretion does not mean the presence of atrophy of the stomach antral mucosa. Thus, the detection of atrophic gastritis by screening strategies of the first line is carried out by determination of the levels of postprandial gastrin-17, and fasting pepsinogen-I and pepsinogen-II in blood serum. In addition, it is necessary to calculate the ratio of pepsinogen-I/pepsinogen-II. The conclusion about the presence or absence of atrophic gastritis, based on the results of the serological examination, should be made on the basis of Tables 2 and 3, which are presented below.

Table 2 Serological criteria for the assessment of atrophic gastritis.

No	Indicator	Normal	Signs of atrophic gastritis
1	Gastrin-17 (postprandial)	> 10 pmol/L	< 10 pmol/l-a sign of atrophic gastritis of the antrum
2	Pepsinogen-I	> 30 μg/L	< 30 μg/l-a sign of atrophic gastritis of the corpus
3	Anti-HP IgG	< 30 EIU	> 30-a sign of Helicobacter pylori positive gastritis

Table 3 Serological criteria for the assessment of atrophic gastritis.

No	Indicator	Normal	Signs of atrophic gastritis
1	Ratio pepsinogen-I/pepsinogen-II	> 3	< 3-an integral sign of atrophic gastritis
2	Anti-HP IgG	< 30 EIU	> 30-a sign of Helicobacter pylori positive gastritis

Criteria for the assessment of atrophy markers are given for the GastroPanel^®biohit test panel.

According to serological criteria of varying severity of atrophy for the antrum and for the body of the stomach, the severity of atrophy of the gastric mucosa can be determined. In turn, the severity of the atrophy allows to estimate the risk of developing stomach cancer. The Kyoto Consensus has divided chronic atrophic gastritis, depending on the risk of stomach cancer, into two levels. The detection of the mild and moderate gastric atrophy corresponds to the low risk of stomach cancer, while severe gastric mucosal atrophy is an indicator of high risk of stomach cancer development[10]. The risk of stomach cancer should be determined based on Tables 4 and 5, which are presented below. The flowchart is shown in Figure 1.

Figure 1 Flowchart of serological screening with GastroPanel^®biohit test panel. G-17 > 10 pmol/L, PG-1 > 25 mkg/L: No atrophy.

Table 4 Assessment of gastric cancer risk in patients with atrophic gastritis.

No.	The risk level of gastric cancer	The degree of stomach mucosal atrophy	Antrum (gastrin-17 pmol/L)	Corpus (pepsinogen-1 μg/L)
1	Low	No atrophy	> 10	> 25
2	Low	Mild	7-10	15-25
3	Low	Moderate	4-7	9-15
4	High	Severe	0-4	0-9

Table 5 Serological criteria for determining low and high risk of gastric cancer.

Localization	Gastric corpus-PG-1 (μg/L)
Gastric antrum-G -17 (pmol/L)	Serology	0 (> 25)	1 (> 25)	2 (15-25)	3 (9-15)	4 (0-9)
	0 (> 10)	1	1	1	2	5
	1 (> 10)	1	2	2	2	5
	2 (7-10)	2	2	2	3	5
	3 (4-7)	2	2	4	5	10
	4 (0-4)	18	18	36	36	90

0: Normal stomach; 1: No atrophy; 2: Mild atrophy; 3: Moderate atrophy; 4: Severe atrophy.

Patients with serologically determined severe gastric mucosal atrophy should be referred to the screening strategies of the second line.

In summary, the advantages of serological screening for the detection of atrophic gastritis are as follows: (1) It allows for the primary non-invasive detection of gastric mucosal atrophy by assessing the levels of serological markers of atrophic gastritis in the antrum and the body of the stomach; (2) It substantially shortens the number of patients exposed to the screening strategies of the second line (endoscopic and histological stages of diagnosis), as only patients with serologically detected severe atrophy with a high risk of developing stomach cancer are referred; and (3) Noninvasive screening of severe gastric mucosal atrophy reduces the number of patients exposed to screening strategies of the second line, which significantly reduces the financial costs for performing the high-tech diagnostic methods.

Morphological markers of varying degrees of atrophy of the stomach mucosa of the antrum and the body were paired with serological markers. As a result, it allowed to determine the risk level of GC based on the serological criteria of mild, moderate and severe atrophy[11]. Rugge et al[12] proposed a system Operative Link on Gastritis Assessment (OLGA) for the stratification the risk of GC development in atrophic gastritis. We have undertaken testing of this system based on the combination of serological and histological examination data. Our results show the acceptability of using serological screening to monitor patients at high risk of developing cancer; that allowed us to propose the serological criteria for determining the stages of atrophic gastritis according to the classification OLGA. The OLGIM system-determines the stage, form and extent of intestinal metaplasia. Both systems together assess the risk of developing GC. Intestinal metaplasia should be diagnosed at the second stage using endoscopic and histological methods[12]. Kotelevets SM, Chekh SA proposed to evaluate histological and serological markers of gastric mucosa atrophy according to the OLGA classification[13]. The scheme of OLGA system and the results of our study are presented in Tables 6 and 7.

Table 6 Determination of the stages of atrophic gastritis by classification Operative Link on Gastritis Assessment.

Atrophy antrum	Corpus
	No atrophy	Mild atrophy	Moderate atrophy	Severe atrophy
No atrophy	Stage 0	Stage I	Stage II	Stage III
Mild atrophy	Stage I	Stage I	Stage II	Stage III
Moderate atrophy	Stage II	Stage II	Stage III	Stage IV
Severe atrophy	Stage III	Stage III	Stage IV	Stage IV

Table 7 Serological criteria the stages of atrophic gastritis Operative Link on Gastritis Assessment.

Localization	Gastric corpus-PG-1 (μg/L)
Gastric antrum –G-17 (pmol/L)	Serology	> 25	15-25	9-15	0-9
	> 10	Stage 0	Stage I	Stage II	Stage III
	7-10	Stage I	Stage I	Stage II	Stage III
	4-7	Stage II	Stage II	Stage III	Stage IV
	0-4	Stage III	Stage III	Stage IV	Stage IV

Thus, patients with severe atrophic gastritis detected by serological screening have a high risk of stomach cancer. These patients should be referred to the screening strategies of the second line-invasive, including endoscopy with biopsy and subsequent histology.

Patients with severe atrophy detected in at least one of the screening strategies of the second line: Diagnostic endoscopy with biopsy of patients with positive serological markers of gastric mucosal atrophy.

At the stage of invasive screening, the patient undergoes an endoscopic examination followed by a biopsy for histology. Endoscopic technologies currently make it possible to visualize changes in the mucosa in detail, to carry out their qualitative and morphometric assessment, and to identify the areas suspicious for precancerous changes with a high degree of accuracy[14,15]. Despite the endoscopic diagnosis of precancerous changes has achieved significant success, the diagnostic potentials of histological recognition of precancerous changes in the gastric mucosa have not lost their significance. The histological examination of gastric mucosal specimens allows assess the stages of gastric carcinogenesis and precancerous changes in the gastric mucosa very correctly[16,17]. Conventionally, five biopsies of the gastric mucosa taken in accordance with the Sydney system are subjected for morphological assessment. In 1969, Kimura and Takemoto proposed a new classification of atrophic gastritis. According to this classification, atrophy was assessed by the area of the lesion of the stomach surface. The biopsy procedure (four biopsies-two each from the antrum and body) practically does not differ from the sampling scheme of the Sydney system, and the morphological characteristic reflects the successive stages of the spread of atrophic changes. Kimura and Takemoto identified six consecutive stages of atrophy development from the antrum to the cardiac part of the stomach: C1-C3, O1-O3. The open -O and closed -C types were also distinguished. According to the updated classification of atrophic gastritis by Kimura and Takemoto, a biopsy must be taken from six points. As a result, the sensitivity of morphological detection of atrophy is significantly increased: Mild by four times, moderate by three times, severe by two and a half times[18]. Thus, Kimura-Takemoto classification allows a more objective assessment of the coverage area of the atrophic process of the gastric mucosa. Histological assessment of precancerous changes in the gastric mucosa should be carried out in accordance with the standard of the updated Sydney system using a visual analog scale. This scale provides a semi-quantitative assessment of the severity of atrophy in each biopsy sample, and in addition, the level of H. pylori contamination, the severity of intestinal metaplasia, as well as the severity of inflammatory infiltration separately evaluated for mononuclear elements (chronic inflammation) and neutrophilic leukocytes (activity). The criterion for assessing the severity of atrophy is a lack of 60% of glands for severe atrophy, loss of glands from 30% to 60% for moderate and absence of less than 30% of gastric glands for mild atrophy (Table 8).

Table 8 Histological criteria of atrophy according to visual analogue scale.

The degree of atrophy in the biopsy	The percentage of loss of gastric glands
Mild atrophy	Less than 30% of the glands are lost
Moderate atrophy	Loss of glands is 30%-60%
Severe atrophy	Loss of more than 60% of the glands

According to our data, the most accurate and effective histological assessment of the severity of atrophic gastritis is revealed in biopsies performed in accordance with the updated classification of Kimura-Takemoto atrophic gastritis. Сomparative study of the method of obtaining biopsies and their histological assessment showed the advantage of detecting atrophic gastritis of varying severity in accordance with the updated classification of atrophic gastritis of Kimura-Takemoto compared with the updated Sydney system[18]. six biopsies obtained according to the updated Kimura-Takemoto classification of atrophic gastritis should be subjected to endoscopic monitoring of the stomach at least once a year. In summary, the strategies for the diagnosis of the precancerous conditions of the stomach should be organized in the manner that provides the possibility of assessment of large groups of population, especially in known areas with high risk of GC incidence. At the first stage, these strategies should be non-invasive and inexpensive, but still capable of providing reliable, highly informative results. Based on the results of large-scale screening, a group of patients with a high risk of developing stomach cancer should be identified based on the diagnosis of atrophic gastritis with severe atrophy. In this group of patients, an invasive diagnosis of atrophic gastritis is used with an assessment of the risk of developing stomach cancer.

MARKERS FOR DETECTION OF ATROPHIC GASTRITIS FOR PROGNOSIS OF GC

Markers of atrophic gastritis are used for its detection in population screening. This is a frequent use of serological markers. The relevance of using the GastroPanel^® test panel continues today[19]. The use of such a marker as H. pylori for the detection of gastric precancer will also be effective[20]. A pan-specific marker is S100a8 for CD11b+Ly6G+ cells that occur in chronic inflammation of the stomach, which worsens the metaplastic pathology of the mucosa[21]. The role of other genetic markers of precancerous changes in the gastric mucosa is very important. It has been shown that a single nucleotide polymorphism (SNP) in the autophagy gene ATG16 L1 (rs2241880, G-allele) causes the progression of precancerous changes in the gastric mucosa[22]. Confirmation of the carcinogenic effect of deoxycholic acid (DCA), which is the main component of bile acid of duodenogastric reflux, was obtained in experimental models. Therefore, DCA and duodenogastric reflux can be considered as a marker of gastric carcinogenesis[23]. MicroRNA gastrokine 3 is a specific marker of gastric corpus metaplasia in mice and may be considered as a promising marker of carcinogenesis and gastric precancer in humans[24]. Specific markers for the gastric corpus and antrum exist in addition to the traditional serological markers gastrin-17 and pepsinogens. Ninety-one protein is reduced in the tissues of the gastric corpus in atrophic gastritis and interleukin-6, human epididymal protein 4 are reduced in antral atrophic gastritis[25,26]. Positive antibodies to parietal cells, as well as antibodies associated with systemic lupus erythematosus, autoimmune thyroiditis, antinuclear antibodies can serve as markers of precancerous lesions in the stomach[27]. More and more studies are devoted to the association between long non-coding RNA and precancerous lesions of the gastric mucosa. The expression level of LINC00659 gradually increases with the progression of atrophic gastritis, intestinal metaplasia and dysplasia. LINC00659 may have the potential to become a new marker for precancerous changes and diseases of the stomach[28]. GC may be associated with Epstein-Barr virus (EBVaGCs) and therefore EBVaGCs may be a biomarker for gastric precancer[29]. The process of gastric carcinogenesis is closely related to the transformation and differentiation of 4 subgroups of fibroblasts in stromal cells. The proportions of fibroblasts differ at different stages of gastric carcinogenesis. The proportions of each subgroup of fibroblasts have a characteristic level of expression of the corresponding markers: PDGFRA, FBLN2, ACTA2 and PDGFRB. Based on such markers, it is possible to make a prognostic model of gastric carcinogenesis from atrophy of the gastric mucosa and intestinal metaplasia to dysplasia[30]. Some substances are markers of anti-carcinogenesis and reflect the regression of precancerous changes. For example, quercetin inhibits cell proliferation and promotes apoptosis. Such markers can be used to effectively monitor the treatment of precancerous changes[31]. In addition to markers of precancerous changes in the gastric mucosa and precancerous disease (atrophic gastritis), markers of GC are being intensively studied. It has been established that the expression of DSCC1 and GINS1 increases in GC and genes associated with SPAG5 and ASPM, are overexpressed in GC tissues[32,33]. 5-hydroxytryptamine and the LGR5 are markers of precancerous mucosal changes and GC simultaneously[34].

RISK FACTORS FOR PROGNOSIS OF GC DEVELOPMENT

The main risk factors for GC have long been identified. These include age, H. pylori infection, male gender, smoking, farmer's profession, low annual family income, illiteracy, alcohol consumption, hot food consumption, fast food intake, history of gastritis, peptic ulcer disease and gallbladder disease[35]. In developed countries, GC is largely associated with H. pylori[36]. Smoking and alcohol consumption are considered proven risk factors for the occurrence and development of GC[37,38]. Nicotine is the main risk factor in tobacco smoking. It stimulates mutagenesis, as well as tumor angiogenesis and metastasis[39]. People with low levels of education and victims of socioeconomic inequality were more likely to develop neoplastic lesions[40]. Additional risk factors for GC are recent (Table 9).

Table 9 Gastric cancer risk structure.

Risk factors for gastric cancer
Main risk factors	Additional risk factors
Age	Absence healthy lifestyle
Helicobacter pylori infection	Underweight or overweight significantly
Male gender	Periodontosis
Smoking
Farmer's profession
Low annual family income
Illiteracy
Alcohol consumption
Hot food consumption
Fast food intake salt consumption
History of gastritis
Peptic ulcer disease
Gallbladder disease, bile reflux
Genetic factors

These include lack of healthy lifestyle associated with geographic differentiation. For example, the Asia-Pacific region[41]. An important additional risk factor for GC is body mass index. Being underweight or overweight significantly increases the risk of GC[42]. Periodontosis is also a very important risk factor for GC. Mechanisms of gastric carcinogenesis in periodontal diseases have been identified. Lipopolysaccharide Porphyromonas gingivalis has a carcinogenic effect on the gastric mucosa[43]. Genetic studies aimed at identifying SNPs associated with the risk of GC have good prospects. Based on them, it is possible to make polygenic risk score[44]. A promising area of research is the identification of prognostic genes on the basis of which it is possible to construct signatures for predicting the long-term risk of GC[45].

DISCUSSION

Unfortunately, patients with advanced GC continue to seek medical care only after the onset of clinical symptoms (92.1% in Tanzania)[46]. In recent years, experience has been accumulated in the modern promising methods for the diagnosis of precancerous diseases and changes in the gastric mucosa, as well as the possibilities of their treatment. It is very important to accurately diagnose precancerous changes in the gastric mucosa, including intestinal metaplasia (complete, incomplete), dysplasia (low-grade, high-grade intraepithelial neoplasia). Scientific material is accumulating on the problem of stopping the progression of gastric carcinogenesis and regression of precancerous pathology of the stomach. Endoscopic imaging and histological confirmation are the main diagnostic methods for verifying precancerous diseases and changes in the gastric mucosa. The sensitivity, specificity and accuracy of these diagnostic methods are highly questionable, since no correlation was found when evaluating the results. The results of esophagogastroduodenoscopy and morphological biopsy samples were obtained in 16764 patients of the French population[47]. The question arises, which method should be used as the gold standard, endoscopic or morphological? The answer, in our opinion, should be sought in improving the criteria for their assessment and accurate identification. The use of the most modern endoscopic and morphological technologies (narrow-band imaging, visualization in white and blue light, endoscopy with magnification, confocal laser endomicroscopy, the use of a visual analog scale to assess histological changes in the gastric mucosa, expert morphometry) does not exclude the negative influence of subjective evaluation of imaging results by an endoscopist and a pathologist. The successful solution of complex diagnostic tasks is possible only through the introduction and use of objective assessment methods using artificial intelligence, convolutional neural networks with deep machine learning. The introduction of modern digital technologies and artificial intelligence is a good resource for improving the accuracy of diagnosis of precancerous gastric pathology in both endoscopic and morphological diagnostics. The use of artificial intelligence based on deep machine learning in the endoscopic diagnosis of atrophic gastritis shows greater accuracy (93%) than the results of endoscopists[48,49]. We allow ourselves to express great hope that the use of artificial intelligence to visualize histological images will increase the accuracy and effectiveness of morphological diagnostics. The French authors have revealed interesting patterns in the development of precancerous gastric pathology during long-term dynamic endoscopic and morphological observation on a large clinical material. Five hundred and seven patients were monitored for 66 months. During this period, each patient underwent four endoscopies with biopsy and histological examination of 9 biopsy samples. Stability of the endoscopic and morphological status was observed in 70% of patients. Progression of lesions was observed in 14%, regression of lesions was determined in 16%[50]. A systematic review and meta-analysis by Chinese authors presents the results of dynamic follow-up of patients with precancerous gastric lesions after eradication. Eradication therapy can stop the progression of precancerous lesions of the stomach, and their regression is possible after treatment of H. pylori infection. The authors revealed a clear dependence of the dynamics of precancerous lesions of the stomach on the duration of follow-up, the number of biopsy samples, the localization of biopsies and the treatment regimen. The results of the meta-analysis showed that anti-Helicobacter eradication therapy affected the development of gastric precancerous lesions and significantly increased the frequency of regression of precancerous pathology[51]. In addition to ethiotropic eradication therapy, pathogenetic treatment is of great importance in the treatment of precancerous gastric pathology. Traditional Chinese medicine suggests using effective drugs: Weiqi decoction, Manpixiao decoction, Banxia Xiexin decoction, Huangqi Jianzhong decoction, Berberine - an alkaloid of Coptis Chinensis, Dendrobium officinale, Ginkgo Biloba extract, Acupuncture. Ginseng root, turmeric root extract and Astragalus membranaceus root were also effective. Western medicine offers nonsteroidal anti-inflammatory drugs, vitamins A, C, E and folic acid for the pathogenetic treatment of precancerous changes in the stomach. The above-mentioned pathogenetic drugs have an antioxidant, immunomodulatory effect, and also correct apoptosis, cell proliferation and the level of inflammatory cytokines. The ability of drugs to regulate the expression of certain proteins and genes motivates researchers to search for new effective methods of treating precancerous gastric lesions[52,53]. The practical application of the above recommendations in the state republican program for the prevention of GC in the Karachay-Cherkess Republic demonstrated significant effectiveness over seven years of observation. Among the patients who took part in the program of screening, diagnostics, monitoring and treatment for seven years, no cases of GC were detected. Among the same number of the population of the Karachay-Cherkess Republic who did not participate in the program, more than four people fell ill with GC over seven years. A large number of identified patients in population requires the creation of a regional registry with machine processing of the results obtained for accounting and dynamic control[13]. The authors hope that the use of practical recommendations on prevention will make it possible to change the situation in a positive way.

CONCLUSION

Practical hints for population-based serological screening of atrophic gastritis, endoscopic and morphological verification of precancerous changes and diseases of the stomach, as well as their treatment are recommended for use: When developing state programs for the prevention of stomach cancer; when implementing preventive measures for stomach cancer by doctors of all specialties; the authors also offer the possibility of use by anyone over the age of 40, provided that they seek methodological help from their doctor; in the work of health schools in any medical and preventive institutions. To increase the effectiveness of the implementation of practical recommendations for the prevention of GC, it is necessary to comprehensively use modern markers of atrophic gastritis and precancerous changes in the gastric mucosa. The use of an assessment system of certain risk factor signatures with prognostic value would add significant assistance to preventive measures against GC.