Abstract
Autoimmune gastritis is an alternative cause of gastric carcinogenesis. This cause may be gaining importance with declining prevalence of chronic Helicobacter pylori infection. To determine the association of prediagnostic autoantibodies to gastric mucosa with gastric cancer (GC) risk. This cohort study used nested GC case-control analyses within separate Finnish cohorts of women of reproductive age (Finnish Maternity Cohort [FMC]; born 1938-1989) and older men (Alpha-Tocopherol, Beta-Carotene Cancer Prevention [ATBC] Study; born 1916-1939). There were 529 and 457 matched pairs from the FMC and ATBC Study, respectively, with mean participant ages of 30.5 and 57.5 years and medians of 17 and 11 years from baseline to cancer diagnosis. Data analyses were performed between August 2019 and November 2020. Antiparietal cell antibodies (APCAs), anti-intrinsic factor antibodies, and anti-H pylori antibodies were measured in baseline serum using immunoassays. Autoantibody associations were estimated by odds ratios (ORs) and 95% CIs. Of the 529 control participants in the FMC and 457 control participants in the ATBC Study, 53 (10%) women and 35 (7.7%) men were APCA seropositive, respectively, whereas 146 (28%) women and 329 (72%) men were H pylori seropositive. In the FMC, APCA seropositivity was statistically significantly associated with GC risk among H pylori-seronegative women (OR, 5.52; 95% CI, 3.16-9.64) but not H pylori-seropositive women (OR, 1.29; 95% CI, 0.64-2.60; P for interaction = .002). The APCA association with H pylori seronegativity was strongest for tumors in the fundus and corpus (OR, 24.84; 95% CI, 8.49-72.72). In the ATBC Study, APCA seropositivity was not associated with GC among either H pylori-seronegative men (OR, 0.99; 95% CI, 0.32-3.04) or H pylori-seropositive men (OR, 1.06; 95% CI, 0.60-1.88). In both cohorts, anti-intrinsic factor antibody seroprevalence was less than 2% among cases as well as controls and not statistically associated with GC risk. Results of this cohort study demonstrate that autoantibody positivity may reflect subclinical autoimmune gastritis in younger women. The findings among young females and corpus subsite align with increasing cancer incidence trends for these groups. Stronger autoimmune associations in H pylori-seronegative individuals support a model of autoimmune gastritis replacing H pylori as the driving factor.
Highlights
Participants in the Finnish Maternity Cohort (FMC) were substantially younger than participants in the ATBC Study at time of blood collection; participants with gastric cancer (GC) in the FMC were younger than in the ATBC Study at diagnosis
Antibody Associations With GC In both cohorts, baseline H pylori seroprevalence was higher among GC cases than controls: 394 of 529 (74.5%) vs 146 of 529 (27.6%), respectively, for the FMC, and 399 of 457 (87.3%) vs 329 of 457 (72.0%), respectively, for the ATBC Study (Table)
The odds ratio (OR) for the association of H pylori seropositivity with cancer risk were 7.38 in the FMC and 2.81 in the ATBC Study
Summary
Study Population Participants with GC and controls were identified from 2 prospective population-based cohorts. The Finnish Maternity Cohort (FMC) was established in 1983 by the National Public. AIFAs were analyzed using commercially available enzyme-linked immunosorbent assay (ELISA) kits (IBL International GmbH). Anti–H pylori whole-cell IgG antibody was tested by ELISA kits from IBL International GmbH for FMC samples and from Biohit Healthcare for ATBC Study samples. Both of these assays have comparable high sensitivity and specificity.[18] For IBL International GmbH products, qualitative results were determined from the cutoff index calculated as the optical density of the sample divided by the mean optical density of the cutoff standard, with a cutoff index of 1 or greater considered seropositive. All laboratory analyses were conducted at the University of Oulu in Finland and blinded to case-control status
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