New Pattern in Gastric Cancer: One Type Increasing in US

Pam Harrison

January 31, 2018

The epidemiology of gastric cancer is changing in the United States, say researchers. Incidence rates of noncardia gastric cancer are rising among individuals younger than 50 years, although it's falling in older patients. Women will soon be more at risk than men.

The findings were published online January 19 in the Journal of the National Cancer Institute.

The data show "a new pattern in gastric cancer epidemiology," Martin Blaser, MD, and Yu Chen, MD, New York University School of Medicine in New York City, write in an accompanying editorial.

"This pattern appears to identify a new form of noncardia stomach cancer," they add.

The rising incidence of noncardia gastric cancers in individuals younger than 50 that is reported in the current study — together with the fact that the largest increase in noncardia gastric cancer involves tumors in the gastric corpus and that women are more at risk of developing corpus cancer than men — suggests that a new type of gastric cancer is taking hold in the United States, defined by the editorialists as "CYF" cancers — corpus-dominant, young age–dominant, female-dominant gastric cancers.

"Gastric cancer has always been more common in men, but these data in women predict an unprecedented reversal," Dr Blaser and Dr Chen write.

Driven by Infection or Autoimmunity?

"The initial step for noncardia gastric carcinogenesis is atrophic gastritis, driven by either Helicobacter pylori infection or autoimmunity," note the study authors, led by William Anderson, MD, MPH, National Cancer Institute, Bethesda, Maryland.

However, in recent years, the prevalence of H pylori has declined significantly, not only in the United States but also globally, they note. At the same time, the prevalence of autoimmunity has increased as Western lifestyles change.

These two trends prompted investigators to see whether there has been a shift in the incidence of gastric cancer as well as in the type of gastric cancer manifested in the US population across almost 2 decades.

To track the incidence of gastric cancer, they mined data from 1995 to 2013 in the National Cancer Institute's Surveillance, Epidemiology, and End Results database and in 45 North American Association of Central Cancer Tumor Registries (NAACCR).

These data represent about 80% of the US population.

"There were 137,447 noncardia cancers in 4.4 billion person-years of observation," the investigators report.

The majority of the adenocarcinomas recorded in the NAACCR database were found in non-Hispanic whites; people aged 50 years or older at the time of diagnosis; and in counties were rates of poverty were less than 20%, they add.

However, incidence rates varied considerably, depending on ethnicity.

For example, age-standardized rates (ASRs) of noncardia gastric cancer were 2.2 per 100,000 person-years among non-Hispanic whites; 6.2 per 100,000 person-years for non-Hispanic blacks; and 7.7 per 100,000 person-year for non-Hispanic others, primarily Asians.

The sites involved in these cancers — and their incidence rates over the years — also varied considerably, depending on sex and age.

Confining their analysis to non-Hispanic whites — the only race in which significant changes in the epidemiology of noncardia cancer were seen — "12.8% of noncardia cancers were localized to the gastric fundus, 19.8% to the corpus, 35.0% to the antrum, and 5.5% to the pylorus," the study authors report.

Regarding the estimated annual percentage change (EAPC) in the incidence of these cancers, the researchers found that overall, the incidence for noncardia cancer dropped by 3% per year (95% confidence interval [CI] = -3.3% to -2.7%) between 1995 and 2013.

On the other hand, incidence rates did not drop uniformly between these years, and they were age-dependent.

Table. EAPC for Noncardia Cancers per Year Over Time

Men -1.7% (95% CI = -2.0 to -1.4%)
Women -2.3 % (95% CI = -2.6% to -2.0%)
Men and women younger than 50 years +1.3% (95% CI = 0.6 to 2.1%)
Men and women aged 50 years or older -2.6% (95% CI = -2.4% to -2.9%)
Women younger than 50 years +2.6% (95% CI = 1.7% to 3.4%)
Women aged 50 years or older -2.2% (95% CI = -2.5% to -1.9%)


Expected Trends

The researchers also compared current trends of noncardia cancer incidence rates among non-Hispanic whites between 1995 and 2013 and expected rates between 2014 and 2030, again stratified by age and sex.

They observed that in 2005, age-standardized rates for individuals younger than 50 years began to reverse. For a lengthy period before that time, noncardia gastric cancers were predominantly seen in males; since that time, such cancers have been increasingly seen in females.

"By 2020, the long-term falling ASRs for all ages combined are expected to stabilize for men and increase for women," the authors observe — and by 2025, the researchers anticipate that the incidence of noncardia cancer among women will surpass the incidence in men.

Most importantly, women younger than 50 are expected to experience the greatest increase in tumors localized to the gastric corpus.

For this group of women, researchers anticipate an estimated annual percent change of 6% a year, compared to 3% a year for men.

"In contrast, noncardia incidence trends declined for non-Hispanic blacks and for non-Hispanic others, irrespective of age," investigators observe.

Poverty and Cancer Incidence

The authors emphasize that the rising incidence rates of noncardia gastric cancer seen predominantly in non-Hispanic whites occurred only in counties where the prevalence of poverty was less than 20%.

Because H pylori colonization rates tend to be lower among more affluent individuals, noncardia gastric cancer incidence rates logically should be higher in poorer counties, not counties where H pylori colonization rates are presumably the lowest.

On this basis, the authors suggest that factors other than H pylori may be responsible for the trends observed between 1995 and 2013 among non-Hispanic whites.

These factors might include a higher prevalence of autoimmune gastritis, which disproportionately affects women and is thought to play an important causal role in corpus-predominant gastritis.

Alternatively, decades of exposure to antibiotics, again disproportionately used by women, may have altered the gut microbiome to such an extent that it, too, might be contributing to autoimmune gastritis and the subsequent promotion of noncardia gastric cancer in women younger than 50.

In their editorial, Dr Blaser and Dr Chen also speculate on what factors might be contributing to this new variant of noncardia gastric cancer.

They also highlight the fact that H pylori has been progressively disappearing everywhere, and suggest that replacement microbes may be particularly injurious to the gastric mucosa.

The editorialists also suggest that the incidence of gastroesophageal junction (GEJ) cancers, which were first seen in the United States around 1970, are really occurring in birth cohorts born after the turn of the 20th century.

"In non-Hispanic whites in the United States, the incidence of GEJ cancers is now higher than the traditional noncardia gastric cancers," they observe.

"Much evidence shows a strong inverse relationship of H pylori with GEJ cancers," they add — a confirmation that the observed fall in the incidence of distal gastric cancer in the United States and the concomitant rise in the incidence of GEJ cancers reflect the disappearance of H pylori across the country.

"[I]n cohorts beginning in the early 20th century, the changes [in gastric microecology] fueled the rise of the GEJ adenocarcinomas, Stage III, occurring chiefly in the post-World War II birth cohorts [and are] fueling the CYF cancer increases," they argue.

"This timing parallels the antibiotic era, possibly reflecting the dysbioses caused by substantial exposures," Dr Blaser and Dr Chen add.

They also agree with the study authors that increases in CYF noncardia gastric cancer might also involve autoimmunity — "either primary or secondary to microbiota change," they suggest.

The study was supported by the Intramural Research Program of the National Institutes of Health and the National Cancer Institute. The authors have disclosed no relevant financial relationships.

J Natl Cancer Inst. Published online January 19, 2018. Full text, Editorial

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