Risk Factors and Incidence of Gastric Cancer after Eradication of Helicobacter pylori

Abstract

I read with interest the article by Kumar et al1Kumar S. et al.Gastroenterology. 2020; 158: 527-536Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar on a large cohort study concerning gastric adenocarcinoma (GAC) and eradication of Helicobacter pylori (HP). They concluded that, if the eradication of HP were successful, the incidence of GAC would decrease. In fact, according to their data, the incidence of GAC decreased to less than one-half that of the noneradicated group 5 years after eradication. Therefore, their results seem to justify massive promiscuous HP eradication to decrease the incidence of GAC. However, such cohort studies may be inconsistent with actual country-level gastric cancer prevention effects. The Japanese government approved an HP-eradication therapy strategy for individuals with peptic ulcers in 2000 and further extended this therapy to every HP-positive person in 2013. Since 2001, >10 million people have already eradicated HP, but the age-adjusted mortality rate of GAC has not changed on the regression line.2Uno Y. Cancer Med. 2019; 8: 3992-4000Crossref PubMed Scopus (16) Google Scholar In addition, the age-adjusted incidence of GAC changed in 2002, with the regression line taking an upward slope, and the incidence is increasing yearly.3Matsuno K. et al.J Gastroenterol. 2019; 54: 784-891Crossref PubMed Scopus (25) Google Scholar Furthermore, in 2018, the highest number of new cases of gastric cancer was recorded.2Uno Y. Cancer Med. 2019; 8: 3992-4000Crossref PubMed Scopus (16) Google Scholar What is the cause of these differences between Japanese reality and cohort study results? In the United States, which has many ethnic groups, GAC incidence may be affected by factors such as differences in HP genes, Cag A, salinity, and diet, unlike populations with single ethnic groups such as Japan. However, an important result from Kumar et al1Kumar S. et al.Gastroenterology. 2020; 158: 527-536Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar is that GAC among HP-infected individuals occurred in older people. Similarly in Japan, the prevalence of GAC increases with advancing age and exponentially increases from the age of 50 years. For such a population, even if the age difference between the 2 groups being compared is small, the incidence is greatly affected. Therefore, to compare the effects of eradicating HP, it is necessary to compare eradicated and noneradicated groups of the exact same age group. However, even in the same age group, the population composition of the eradication group may change owing to the effects after eradication. A US epidemiological study comparing an HP antibody-negative group with an HP antibody-positive group showed that the negative group had a low gastric cancer mortality rate, but a high risk of dying from diseases other than gastric cancer.4Chen Y. et al.Gut. 2013; 62: 1262-1269Crossref PubMed Scopus (77) Google Scholar In the long term after HP eradication, the possibility of acquiring the negative characteristics of an uninfected person cannot be denied. In fact, reflux esophagitis, Barrett's esophagus, and esophageal adenocarcinoma have been confirmed to increase after HP eradication.2Uno Y. Cancer Med. 2019; 8: 3992-4000Crossref PubMed Scopus (16) Google Scholar,5Iijima K. et al.Front Microbiol. 2015; 6: 566PubMed Google Scholar In long-term observations of HP-positive people in Korea, the number of deaths other than from GAC increased by >5 times in the HP-eradicated group compared with the placebo group.6Choi I.J. et al.N Engl J Med. 2018; 378: 1085-1095Crossref PubMed Scopus (297) Google Scholar In addition, meta-analysis studies have confirmed increased non-GAC mortality after eradication (hazard risk, 1.03).7Terasawa T. et al.BMJ Open. 2019; 9e026002Crossref PubMed Scopus (2) Google Scholar If other diseases are caused by eradication of HP, causing death more often before the age at which GAC occurs, the group's incidence of GAC will decrease (see Figure 1B). In conclusion, to evaluate the decrease in GAC incidence in relation to HP eradication, it is a precondition to prove that the HP-eradication group is not a young population and that deaths other than gastric cancer have not increased. Risk Factors and Incidence of Gastric Cancer After Detection of Helicobacter pylori Infection: A Large Cohort StudyGastroenterologyVol. 158Issue 3PreviewNearly all studies of gastric adenocarcinoma in the United States have relied on national cancer databases, which do not include data on Helicobacter pylori infection, the most well-known risk factor for gastric cancer. We collected data from a large cohort of patients in the United States to calculate the incidence of and risk factors for nonproximal gastric adenocarcinomas after detection of H pylori. Secondary aims included identifying how treatment and eradication affect cancer risk. Full-Text PDF