Evidence from pathology and epidemiology studies has been provided for a human model of gastric carcinogenesis with the following sequential stages: chronic gastritis; atrophy; intestinal metaplasia; and dysplasia. The initial stages of gastritis and atrophy have been linked to excessive salt intake and infection with Helicobacter pylori. The intermediate stages have been associated with the ingestion of ascorbic acid and nitrate, determinants of intragastric nitrosation. The final stages have been linked with the supply of beta-carotene and with excessive salt intake. Nitrosating agents are candidate carcinogens and could originate in the gastric cavity or in the inflammatory infiltrate.

https://cancerres.aacrjournals.org/content/canres/52/24/6735.full.pdf

Human Gastric Carcinogenesis: A Multistep and Multifactorial Process—First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention

Vitamin C and cancer prevention: the epidemiologic evidence.

The seroprevalence of IgG antibodies to Helicobacter pylori was determined using a standard enzyme linked immunosorbent assay in a population of 749 randomly selected men, aged 30-75 years, from Caerphilly, South Wales. The overall prevalence of H pylori was 56.9%, increasing sharply in middle age from 29.8% in those aged 30-34 to over 59% in those aged 45 or older (p less than 0.0001). Age standardised seroprevalence rates were lowest in combined social class categories I and II (49.2%), intermediate in categories IIIN and M (57.5%), and highest in categories IV and V (62.2%) (p = 0.01). In those aged 30-34 years, the prevalence rate for those in combined social class categories IV and V was 57.9% - double the rate for social class categories IIIM and N (28.3%) and five times the prevalence rate in those in social class categories I and II (11.1%). These differences in the infection patterns of H pylori by social class are consistent with patterns of peptic ulcer disease and gastric cancer.

https://gut.bmj.com/content/gutjnl/32/1/25.full.pdf

Helicobacter pylori infection rates in relation to age and social class in a population of Welsh men.

Chronic atrophic gastritis (CAG) is a well-established precursor of intestinal gastric cancer, but epidemiologic data about its occurrence are sparse. We provide an overview on studies that examined the prevalence of CAG in different parts of the world. Articles containing data about the prevalence of chronic atrophic gastritis in unselected population samples and published until November 2005 were identified by searching the MEDLINE database. Furthermore, the references in the identified publications were screened for additional suitable studies. Studies comprising at least 50 subjects were included. Forty-one studies providing data on the prevalence of CAG in unselected population samples could be identified. CAG was determined by gastroscopy in 15 studies and by pepsinogen serum levels in 26 studies. Although results are difficult to compare due to the various definitions of CAG used, a strong increase with age, the lack of major gender differences, and strong variations between populations and population groups (in particular, relatively high rates in certain Asian populations) could be observed quite consistently. We conclude that CAG is relatively common among older adults in different parts of the world, but large variations exist. Large-scale international comparative studies with standardized methodology to determine CAG are needed to provide a coherent picture of the epidemiology of CAG in various populations. Noninvasive measurements of CAG by pepsinogen levels may be particularly suited for that purpose.

https://cebp.aacrjournals.org/content/cebp/15/6/1083.full.pdf

Prevalence of Chronic Atrophic Gastritis in Different Parts of the World

In a cross-sectional study of 634 men aged 40 to 49 years, randomly selected from five areas of Japan with different rates of gastric cancer mortality, 121 men of 624 evaluated were diagnosed as having atrophic gastritis through serum pepsinogen I<70 ng/ml and the pepsinogen I (PGI)/pepsinogen II (PGII) ratio <3.0. We examined the relation of Helicobacter pylori (H. pylori) antibodies and dietary factors, including plasma level of antioxidant micronutrients, to the presence of atrophic gastritis. Presence of H. pylori IgG antibodies was associated with increased risk of atrophic gastritis (odds ratio [OR]=1.9, 95 percent confidence interval [CI]=1.1–3.3). As the level of plasma β-carotene increased, we found a steady decrease in the risk of atrophic gastritis (OR for second quartile = 0.7, third quartile = 0.6, fourth quartile = 0.4, with CI=0.2–0.8). Frequent intake of yellow vegetables also was associated with lower risk, while frequent intake of soybean products was related to increased risk. Although H. pylori antibodies, β-carotene level, and intake of soybean products were all significant in the multivariate analysis, these factors did not explain the differences in atrophic gastritis prevalence among the five regions. The analysis of these risk factors in relation to each pepsinogen marker showed that although both H. pylori infection and low plasma β-carotene were associated with the decreased level of serum PGI/II ratio, the former was derived from the increase of PGII, which is common in early stage of atrophic gastritis, and the latter from the decrease of PGI, which is specific to severe atrophic gastritis. This finding suggests that H. pylori infection is associated with the formation of atrophic gastritis, while β-carotene protects its advancement as well as formation.

Helicobacter pylori, dietary factors, and atrophic gastritis in five Japanese populations with different gastric cancer mortality

A survey was conducted of 513 men aged 65 74 years living in two British towns with high and low stomach cancer death-rates. The prevalence of severe atrophic gastritis (defined as a serum pepsinogen I less than 20 micrograms l-1) was significantly higher in the high-risk than in the low-risk town (14.5% and 7.7% respectively); it also tended to be higher in the manual workers, who are known to have a greater risk of stomach cancer than non-manual workers. The manual workers in the high-risk town were particularly likely to have had a partial gastrectomy. Plasma ascorbate concentration and fruit intake were lower in the high-risk area and lower social classes, suggesting a poorer vitamin C status. There was, however, no direct relationship between ascorbate concentration and the presence of severe atrophic gastritis. These findings are consistent with the hypothesis that risk of stomach cancer is determined in two stages--a long-term effect, producing atrophic gastritis; and a short-term effect in which vitamin C is protective.

I. M. Samloff

Papers

Atrophic gastritis and vitamin C status in two towns with different stomach cancer death-rates.