“True” Helicobacter pylori infection and non‐cardia gastric cancer: A pooled analysis within the Stomach Cancer Pooling (StoP) Project

Abstract

Background Helicobacter pylori is the most important risk factor for non‐cardia gastric cancer (NCGC); however, the magnitude of the association varies across epidemiological studies. This study aimed to quantify the association between H. pylori infection and NCGC, using different criteria to define infection status. Methods A pooled analysis of individual‐level H. pylori serology data from eight international studies (1325 NCGC and 3121 controls) from the Stomach Cancer Pooling (StoP) Consortium was performed. Cases and controls with a negative H. pylori infection status were reclassified as positive considering the presence of anti‐Cag A antibodies, gastric atrophy, or advanced stage at diagnosis, as available and applicable. A two‐stage approach was used to pool study‐specific adjusted odds ratios (OR), and 95% confidence intervals (95% CI). A meta‐analysis of published prospective studies assessing H. pylori seropositivity in NCGCs was conducted. Results The OR for the association between serology‐defined H. pylori and NCGC was 1.45 (95% CI: 0.87–2.42), which increased to 4.79 (95% CI: 2.39–9.60) following the reclassification of negative H. pylori infection. The results were consistent across strata of sociodemographic characteristics, clinical features and lifestyle factors, though significant differences were observed according to geographic region—a stronger association in Asian studies. The pooled risk estimates from the literature were 3.01 (95% CI: 2.22–4.07) for ELISA or EIA and 9.22 (95% CI: 3.12–27.21) for immunoblot or multiplex serology. Conclusion The NCGC risk estimate from StoP based on the reclassification of H. pylori seronegative individuals is consistent with the risk estimates obtained from the literature. Our classification algorithm may be useful for future studies.

Cardia and non‐cardia gastric cancer risk associated with Helicobacter pylori in East Asia and the West: A systematic review, meta‐analysis, and estimation of population attributable fraction

“…Previous studies have consistently illustrated a strong association between H. pylori and NCGC worldwide, although the magnitude of the association varied between studies 6,7,23 . Our results showed a more than fourfold higher risk of NCGC in infected individuals in both East Asia and West.…”

“…Previous studies have consistently demonstrated a significant association between non‐cardia gastric cancer (NCGC) and H. pylori infection; however, the strength of the association varied between studies 6–9 . Furthermore, it remains controversial whether H. pylori infection plays a role in the progression of cardia gastric cancer (CGC), which shows an increasing trend of incidence globally 10 .…”

“…4,5 Previous studies have consistently demonstrated a significant association between non-cardia gastric cancer (NCGC) and H. pylori infection; however, the strength of the association varied between studies. [6][7][8][9] Furthermore, it remains controversial whether H. pylori infection plays a role in the progression of cardia gastric cancer (CGC), which shows an increasing trend of incidence globally. 10 Western studies showed a null or negative association between H. pylori and CGC in contrast to studies in East Asia (China, Japan, and Korea), with a higher risk of CGC in the infected individuals.…”

Considerations in comparing intestinal‐ and diffuse‐type gastric adenocarcinomas

“…Comprehensive literature-based evidence suggests that there is no difference in H. pylori seroprevalence between individuals with intestinal or diffuse tumors. [29][30][31] Notably, long-term prospective studies show that H. pylori infection increases the risk of both Laurén types. 27,32 In agreement, the ABC screening method (based on combined results of H. pylori serology and pepsinogen levels) is useful for the detection of both intestinal and diffuse types.…”

Epidemiology of Gastric Intestinal Metaplasia and Gastric Cancer

“…19,29 H. pylori is a more potent risk factor for non-cardia gastric cancer compared with cardia tumors. 30 Similar to the risk of GIM, CagA gene status plays an important role in the progression to gastric cancer, with a 2.87-fold (95% CI, 1.71-3.05) increase in gastric cancer risk among those infected with a CagA-positive strain of H. pylori. 31 The decline in the incidence of gastric cancer has largely mirrored the decline in H. pylori prevalence.…”