Autoimmune gastritis may be an important factor in gastric cancer

There are many factors that increase the risk of gastric cancer, and Helicobacter pylori is one of them
.
As early as 1994, the World Health Organization defined Helicobacter pylori as a class 1 carcinogen
.

In December 2021, the U.
S.
Department of Health and Human Services (HHS) released the 15th edition of the Carcinogens Report, with eight new carcinogens added to the new report
.
In the latest report, Helicobacter pylori is listed as a clear carcinogen
.

Helicobacter pylori can be controlled and treated in a timely manner with drugs
.
In recent years, with the control of Helicobacter pylori in some countries, the prevalence of gastric cancer caused by Helicobacter pylori has been decreasing
.

Autoimmune gastritis, a cause of gastric cancer, may become increasingly important as chronic H.
pylori infection declines
.
 

Autoimmune gastritis may be an important factor in gastric cancer

Although the incidence of gastric cancer has declined over the past 50 years, gastric cancer remains the fifth most common cancer and the fourth leading cause of cancer death in the world
.

Studies have found that women and the wealthy are more likely to develop stomach cancer
.

Wealthy people have lower rates of Helicobacter pylori infection
.
Therefore, some scholars speculate that autoimmune gastritis (AIG) may be another key factor leading to the occurrence of gastric cancer [3]
.

Autoimmune gastritis is a chronic progressive inflammatory disease in which gastric apical cells are replaced by atrophic and degenerated mucosa
.

The resulting malabsorption and vitamin B12 deficiency are clinically manifested as malignant anemia (PA), which is closely related to the development of gastric cancer
.

Patients with AIG are often asymptomatic, and when patients develop anemia, they may be misdiagnosed or misdiagnosed due to insufficient endoscopic biopsy and/or failure to explore the underlying cause of the anemia
.

On December 16, 2021, Dr.
Min-kyung Song of the National Cancer Institute, NIH, Bethesda, Maryland, published a large prospective study in JAMA[1] with long-term follow-up
.

This study analyzed the relationship between anti-parietal cell antibodies and anti-endogenous factor antibodies and the risk of gastric cancer
.

This study was conducted in Finnish women of childbearing age (Finnish Maternal Cohort [FMC]; born 1938-1989) and older men (-tocopherol, -carotene Cancer Prevention [ATBC] study; born 1916-1939) with gastric cancer Case-control analysis
.

The FMC and ATBC studies had 529 and 457 matches, respectively, with a mean subject age of 30.
5 and 57.
5 years, and a median of 17 and 11 years from baseline to cancer diagnosis
.

The results of this study suggest that autoantibody positivity may reflect subclinical autoimmune gastritis in young women
.

The findings in younger women and subcoronary sulci are consistent with a trend of increased cancer incidence in these groups
.
In H.
pylori-negative individuals, autoimmune gastritis replaced H.
pylori as the driver of gastric cancer
.

In women born after 1938, anti-apical cell antibody (APCA) seropositivity was found to be associated with subsequent gastric cancer, the strength of this association was limited to H.
pylori-negative women, and OR values ​​for fundus and ocular tumors highest
.

In a comparative cohort of older men, APCA and AIFA seropositivity was not associated with gastric cancer but not with H.
pylori serostatus
.

This study is the first attempt to quantify the role of AIG in gastric carcinogenesis
.

Autoimmune gastritis is a well-recognized precursor to pernicious anemia that may develop into gastric cancer, but its quantitative impact on gastric cancer in the general population is unclear
.

Previous studies based on histology rather than serology had smaller sample sizes
.

The report on the association of gastric cancer with AIG is actually an investigation of pernicious anemia
.

In addition, the diagnosis of pernicious anemia is based on questionnaires or vitamin B12 deficiency, the validity of which has not been established
.

A study comparing gastric cancer patients and healthy controls found no association between APCA and AIFA and gastric cancer [5], while another study found that APCA seropositivity was higher in gastric cancer patients than in healthy controls [6]
.

A prospective study from China reported that APCA was inversely associated with cardia adenocarcinoma and not statistically significant with non-cardia gastric cancer, contrary to expectations
.

The authors confirmed an independent association of AIG with gastric cancer, and that different H.
pylori status had different effects on the outcome, suggesting the existence of two groups of cases with different causes
.

Like other autoimmune diseases, AIG is uncommon in men
.
Smoking is inversely associated with the incidence of APCA
.
Conceivably, the men in the ATBC study, who were all smokers, may have had lower rates of APCA than non-smoking men
.

Given the increasing trend of autoimmune diseases, women with FMC are born later, which may explain the higher prevalence of autoantibodies in the ATBC study [9]
.

In addition, the mean age at diagnosis of FMC patients was lower than that in the ATBC study, which is consistent with the relatively younger age distribution of aig-related gastric cancer
.

Advantages and limitations of research on the relationship between autoimmune gastritis and gastric cancer

This study starts from the relationship between autoimmune gastritis and gastric cancer, and has the following four advantages
.

First, the FMC is a unique population-based cohort
.
Most prospective cohort studies of chronic disease outcomes, such as cardiovascular events or cancer, involve participants around middle age
.

The median age of onset of pernicious anemia is 30-39 years old, which means that AIG occurs earlier in this age group
.

Although not included in the cohort of cohorts of men over the same period, it is interesting to assess men from earlier periods that showed no contrast in the autoantibody-gastric cancer association
.

Second, this is the largest prospective study to investigate the relationship between autoantibodies and gastric cancer risk
.

Third, the study took serial samples from the same person over a long period of time to assess changes in antibody levels
.
Notably, the investigator's autoantibody levels did not change over time, supporting the robustness of our findings
.

Fourth, the detection of autoantibodies by commercial ELISAs is highly reproducible and can be reproduced in other studies
.

The study also has some limitations
.
There is currently no information on the possible effect of H.
pylori eradication therapy or other drugs on gastric cancer risk
.
It is currently known that Helicobacter pylori seropositivity is closely related to gastric cancer
.

Autoantibody seropositivity does not necessarily imply the presence of underlying clinical disease
.
APCA and AIFA are also found in other autoimmune diseases, even in healthy individuals
.

It is unclear whether these autoantibodies have a pathophysiological role outside the stomach or reflect an accompanying underdiagnosis of autoimmune disease
.

Future studies should include more diverse populations
.

This study showed that although the prevalence of autoantibodies in the control group did not change much, there was a relative increase in autoantibody-related gastric cancer cases, while H.
pylori-related gastric cancer cases continued to decline in subsequent years
.

These complementary findings provide clues that autoimmune-driven gastric cancer may replace hp ylori as the main driver of gastric cancer
.

As the prevalence of H.
pylori in the general population declines, an autoimmune drive may be an important factor in gastric cancer incidence
.

The increasing trend of autoimmune gastritis in younger generations predicts an increase in the overall incidence of gastric cancer in the future
.

In this cohort study, a new but plausible etiological explanation for this trend and a broader assessment of autoantibodies in patients with gastritis or gastric cancer are presented, which may have implications for reducing the public health burden of gastric cancer provided insights
.
new ideas
.

references

1.
Song M, Camargo MC, Katki HA, et al.
Association of Antiparietal Cell and Anti-Intrinsic Factor Antibodies With Risk of Gastric Cancer.
JAMA Oncol.
Published online December 16, 2021.
doi:10.
1001/jamaoncol.
2021.
5395.

2.