Multiplex H. pylori Serology and Risk of Gastric Cardia and Noncardia Adenocarcinomas

Abstract

The reported associations with gastric adenocarcinoma and seropositivity to different H. pylori antigens using multiplex serology have not been consistent across studies. We aimed to investigate the association between fifteen different multiplex serology antigens and the risk of gastric cardia (GCA) and gastric non-cardia (GNCA) adenocarcinomas in northeastern Iran, a population with high rates of gastric adenocarcinoma. We included 272 cases of gastric adenocarcinoma (142 GCA, 103 GNCA, and 27 unspecified) and 524 controls who were individually matched to cases for age, sex, and place of residence in a population-based case-control study. Seropositivity to H. pylori was assessed using both multiplex serology and H. pylori IgG ELISA. 95% of controls were seropositive to H. pylori. Of the 15 antibodies in the multiplex assay, 11 showed no significant association with gastric adenocarcinomas. CagA and VacA were associated with a significantly increased risk of all gastric adenocarcinoma and GNCA in multivariate models. Surprisingly, GroEL and NapA were significantly associated with a reduced risk of these tumors. Only CagA antigen was associated with significantly elevated risk of GCA. We found no associations between H. pylori seropositivity overall either by whole-cell ELISA test or multiplex serology, likely due to the high prevalence of seropositivity. Individual antigen testing showed that CagA positivity was associated with increased risk of both noncardia and cardia adenocarcinoma, which is similar to some other Asian populations, while two antigens were associated with lower risk of gastric cancer. This latter result was unexpected and should be re-tested in other populations.

Microbial characterization of esophageal squamous cell carcinoma and gastric cardia adenocarcinoma from a high‐risk region of China

“…A meta‐analysis of mostly Western studies showed that the association with H. pylori was found with gastric noncardia cancers (odds ratio, 3.0; 95% confidence interval, 2.3‐3.8) but not with GCA (odds ratio, 1.0; 95% confidence interval, 0.7‐1.4) . However, H. pylori seropositivity is associated with increased risks for GCA in China and Iran but not in other countries such as the United States, Finland, Sweden, and Norway; this suggests that H. pylori may have a distinct association with GCA in China and Iran, perhaps through interactions with other microbiota. Because of these geographic differences, the International Agency for Research on Cancer now includes Asian cardia cancer in their estimates of the H. pylori disease burden .…”

Additive interactions between PRKAA1 polymorphisms and Helicobacter pylori CagA infection associated with gastric cancer risk in Koreans

“…Similarly, a previous Korean study indicated that the association between PRKAA1 rs13361707 and gastric cancer risk did not vary depending on the tumor site [18]. Shakeri et al observed that HP CagA infection was associated with a significantly increased risk not only for cardia, but for noncardia gastric adenocarcinoma [49]. In contrast, several studies reported that the association between PRKAA1 rs13361707 and gastric cancer risk is stronger in noncardia gastric cancer than in cardia cancer [14,17].…”

“…Shakeri et al. observed that HP CagA infection was associated with a significantly increased risk not only for cardia, but for noncardia gastric adenocarcinoma . In contrast, several studies reported that the association between PRKAA1 rs13361707 and gastric cancer risk is stronger in noncardia gastric cancer than in cardia cancer .…”

Diagnostic of Helicobacter pylori infection

“…In Iran, they used 272 GC cases from the Golestan cohort and 524 matched controls. CagA and VacA were associated with an increased risk of noncardia GC while surprisingly the inverse occurred for GroEL and NapA . In Latin America, 1776 residents from Mexico, Colombia, and Chile were divided according to the low‐ and high‐risk areas for GC which both had high H. pylori prevalence.…”