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Lower stomach cancer increasing among young non-Hispanic whites
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The incidence of noncardia gastric cancer, also known as lower stomach cancer, has increased among younger non-Hispanic white individuals since 1995, while declining among older adults, according to study results.
Hispanics showed similar trends; however, incidence declined regardless of age among other races.
“In general, cardia (upper stomach) tumors may start with damage from acid reflux and/or metabolic syndrome, similar to esophageal adenocarcinoma, [whereas] noncardia (lower stomach) tumors are preceded by nonatrophic gastritis and a sequence of increasingly severe mucosal lesions,” M. Constanza Camargo, PhD, Earl Stadtman investigator in the division of cancer epidemiology and genetics at NCI, and colleagues wrote, “Chronic Helicobacter pylori infection is a well-known cause of this pathologic cascade, variably progressing to atrophic gastritis, intestinal metaplasia and dysplasia. However, autoimmune gastritis is increasingly recognized as a contributing etiology, with or without the presence of H. pylori.”
Due to improvements in standard of living and hygiene, as well as widespread use of antibiotics, children are exposed to fewer antigens, which may affect their microbiome and influence cancer risk.
Camargo and colleagues used population-based data from the SEER database and North American Association of Central Cancer Registries to study noncardia gastric cancer incidence rates from 1995 to 2013.
Researchers observed 137,447 noncardia cancers during 4.4 billion person-years of observation. The most cancers occurred among non-Hispanic whites, patients aged older than 50 years and in counties with less than 20% poverty.
Non-Hispanic whites had an age-standardized rate of noncardia cancer of 2.2 per 100,000 person-years and an estimated annual percentage change of –2.3% (95% CI; –2 to –2.6) per year. However, among individuals aged younger than age 50 years, estimated annual percentage change increased 1.3% (95% CI, 0.6-2.1) per year.
This difference appeared especially pronounced among young non-Hispanic white women, who had an estimated annual percentage change of 2.6% (95% CI, 1.7-3.4) per year, compared with –2.2% (95% CI, –2.5 to –1.9) per year among women aged older than 50 years.
Among Hispanics, researchers observed slightly rising rates among those aged younger than 50 years compared with decreasing rates among older individuals.
HemOnc Today spoke with Camargo about the study, the role of antibiotics in this trend and what future research is needed to better understand the growing prevalence of noncardia gastric cancer among younger individuals.
Question: What prompted this research?
Answer: Noncardia gastric cancer has two major known causative factors: chronic infection with the bacterium H. pylori and autoimmune gastritis, in which the immune system attacks cells in the lining of the stomach. These cause overlap, and some patients with noncardia gastric cancer may have both. As Western lifestyles have changed over recent decades, H. pylori prevalence has decreased while autoimmune disorders have increased. Our team was interested in the impact of these shifting risk factors on noncardia stomach cancer incidence across ages and races/ethnicities in the United States.
Q: Are men and women aged younger than 50 years screened for this cancer ?
A: In countries with a high burden of the disease — specifically Korea, Japan and China — upper gastrointestinal endoscopy, with collection of stomach tissue samples and/or X-ray series, are used to screen people aged older than 40 years to detect either stomach cancer or related precancerous lesions. However, stomach cancer risk in the United States is considered to be too low to justify a national screening program.
Q: Can you explain the decline of H. pylori infection and increase of autoimmune gastritis in recent decades?
A: The acquisition of H. pylori mostly occurs in childhood via person-to-person transmission and, without antibiotic treatment, infection remains throughout a person’s life. Presumably due to improvements in sanitation, as well as widespread use of antibiotics, H. pylori infection has been progressively disappearing, particularly in industrialized nations. Thus, the proportion of H. pylori-infected individuals is lower with each succeeding generation. On the other hand, the proportion of people developing allergic and/or autoimmune disorders has been increasing with each generation. We speculate that autoimmune gastritis may be similarly increasing, although there are no firm data on prevalence or incidence. Why these increases are occurring is still uncertain, but a leading hypothesis is that insufficient exposure to microbes during childhood could interfere with maturation of the immune system.
Q: Can you explain why incidence increase d among non-Hispanic white men and women and slightly in Hispanic individuals , but not in other races?
A: Although we did not detect an increase among black and Asian individuals, these groups continue to have higher gastric cancer incidence overall compared with non-Hispanic whites. This difference parallels their higher age-specific prevalence of H. pylori infection, presumably reflecting higher mother-to-child transmission or persistence of lifestyle factors that have historically favored bacterial acquisition during childhood. As H. pylori infection is continuously decreasing, we do not preclude that the unfavorable trends of noncardia stomach cancer in non-Hispanic and Hispanic whites could be observed in other racial groups in the future.
Q: What role might antibiotics play in understanding this increase?
A: Use of antibiotics to treat other infections can sometimes also eradicate H. pylori from the stomach. However, the imbalance of the gastric microbiome associated with H. pylori disappearance may increase an individual’s risk for autoimmune gastritis and consequent noncardia stomach cancer.
Q: Do you think this is a new type of cancer?
A: A classic presentation of a noncardia stomach cancer patient is an older man with a tumor located in the lowest part of the stomach. Our research suggests that in the future many patients with this disease may fit a different demographic profile. Firstly, we observed an increased incidence of noncardia cancer in young generations — individuals aged 50 years or younger. Also, the largest increase is represented by patients with tumors localized to the corpus, the middle part of the stomach. Lastly, within the next 10 years, noncardia stomach cancer incidence is expected to become more common among women than men. These differences are so striking that we call them the “changing face of gastric cancer.”
Q: What are the clinical implications of this study?
Our research is descriptive in nature and not designed to evaluate causality. We hope these findings will be followed up with additional epidemiologic studies, as well as laboratory and animal studies to investigate possible mechanisms that may explain our observations. In particular, research is needed on antibiotic medications that can disrupt the native microbiome of the stomach and may lead to autoimmune gastritis, a cause of noncardia stomach cancer.
Q: What further research is needed ?
A: My colleagues and I are already discussing potential follow-up studies. We are examining available data for stomach cancer incidence trends in other Western populations. We are also planning to evaluate whether the prevalence of autoimmune gastritis is increasing over time in the United States and other populations. – by Cassie Homer
For more information:
M. Constanza Camargo, PhD, can be reached at National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD; email: camargomc@mail.nih.gov.
Disclosure: Camargo reports no relevant financial disclosures.
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