Association of Antiparietal Cell and Anti-Intrinsic Factor Antibodies With Risk of Gastric Cancer

Abstract

IMPORTANCE Autoimmune gastritis is an alternative cause of gastric carcinogenesis. This cause may be gaining importance with declining prevalence of chronic Helicobacter pylori infection.OBJECTIVE To determine the association of prediagnostic autoantibodies to gastric mucosa with gastric cancer (GC) risk. DESIGN, SETTING, AND PARTICIPANTSThis 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.EXPOSURES Antiparietal cell antibodies (APCAs), anti-intrinsic factor antibodies, and anti-H pylori antibodies were measured in baseline serum using immunoassays.MAIN OUTCOMES AND MEASURES Autoantibody associations were estimated by odds ratios (ORs) and 95% CIs. RESULTSOf 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. CONCLUSIONS AND RELEVANCEResults 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.

Management ofHelicobacter pyloriinfection: the Maastricht VI/Florence consensus report

“…91 In populations with low H. pylori prevalence the risk of AIG for the development of gastric cancer, particularly in young females, has recently received much attention and AIG in this context is gaining great importance. 332 For now, it needs to be noted that cases with mild focal atrophy are often grouped together with cases with severe atrophy. OLGA was the first attempt to overcome this problem and showed that stages III and IV in H. pylori infection bear a higher risk for gastric carcinoma than AIG.…”

“…The impact of these findings is reflected in the clinical management by endoscopic/histological follow-up of preneoplastic gastric changes 91. In populations with low H. pylori prevalence the risk of AIG for the development of gastric cancer, particularly in young females, has recently received much attention and AIG in this context is gaining great importance 332. For now, it needs to be noted that cases with mild focal atrophy are often grouped together with cases with severe atrophy.…”

Sex differences in cancer incidence and mortality among patients managed at King Hussein Cancer Center

“…Anti‐estrogen drugs (eg, tamoxifen), diet, or presence of comorbidities among countless other risk factors may predispose females to higher hazard risk to stomach cancer 43,44 . Moreover, recent evidence shows that the presence of autoantibody positivity (ie, antiparietal cell antibodies) is associated with increasing trends of gastric cancer in young women 45 ; such evidence further solidifies the observed risk between autoimmunity and gastric cancer 46 . Finally, the entire observation might be a combination of the aforementioned coupled with suboptimal therapy or lack of effective screening.…”

The Diagnostic Value of Anti-Parietal Cell and Intrinsic Factor Antibodies, Pepsinogens, and Gastrin-17 in Corpus-Restricted Atrophic Gastritis

“…Anti-PCA and anti-IFA antibody values of ≥25 units were considered positive, values between 20.1 and 24.9 units were considered equivocal, and values ≤ 20 units were considered negative [ 22 ]. PGI/II ratio values below 3 were considered decreased and characteristic of corpus atrophy [ 4 ]. G-17 values > 5.0 pmol/L for fasting specimens were considered to be increased and attributed to corpus atrophy, and anti- H. pylori IgG values of ≥30 units were considered positive.…”

“…For example, the prevalence of autoimmune corpus gastritis has increased over the past several decades, especially among younger adults in Northern Sweden [ 3 ]. The association of anti-parietal cell antibodies (anti-PCA) and anti-intrinsic factor antibodies (anti-IFA) with the risk of gastric cancer among Finnish women of reproductive age and older men was recently studied [ 4 ]. The study concluded that pre-diagnostic seropositivity to anti-PCA was associated with an elevated risk of gastric cancer among younger women, but not among older men.…”