Abstract 1053: Associations of anti-parietal cell and anti-intrinsic factor antibodies with gastric cancer risk
Authors: Song Minkyo , Camargo M. Constanza , Katki Hormuzd A. , Weinstein Stephanie J. , Albanes Demetrius , Surcel Heljä-Marja , Rabkin Charles S. 
Published: September 2020

Background: Autoimmune gastritis is an alternative etiology of gastric carcinogenesis. This mechanism may be an increasingly important cause of gastric cancer with waning prevalence of its primary etiologic factor, chronic Helicobacter pylori infection. However, autoimmune gastritis is an infrequent clinical diagnosis. We hypothesized that gastric autoantibodies may reflect subclinical autoimmune gastritis and predict prospective gastric cancer risk.

Methods: We conducted nested case-control studies within two Finnish population cohorts of young females (Finnish Maternity Cohort [FMC], age 16-48, birth years 1938-1989) and older males (Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study [ATBC], age 50-69, birth years 1917-1939). There were 526 and 457 age-, sample time-matched gastric cancer case-control pairs from FMC and ATBC, respectively. Antibodies to parietal cells (APCA), intrinsic factor (AIFA) and H. pylori were measured in serum collected at baseline using commercially available enzyme-linked immunosorbent assays. We estimated odds ratios (ORs) and 95% confidence intervals (CI) for autoantibody associations using conditional logistic regression.

Results: The median time intervals from baseline to cancer diagnosis were 17 years for FMC and 11 years for ATBC. 45% of FMC and 80% of ATBC were H. pylori seropositive. APCA seropositivity in FMC (14%, cases and controls combined) was significantly associated with increased gastric cancer risk among H. pylori seronegative (ORs 4.77 [95% CI 2.81-8.08]) but not H. pylori seropositive individuals (ORs 2.09 [0.91-4.78]). In analyses by anatomic subsite, the APCA association among H. pylori seronegatives was strongest for corpus cancers (OR 17.97 [6.92-46.63]). APCA seropositivity in ATBC (8%) was unassociated with gastric cancer regardless of H. pylori serostatus or anatomic subsite. AIFA seropositivity was 2% in both cohorts.

Conclusion: Our findings of APCA associations with gastric cancer risk in young females and corpus subsite align with increasing cancer incidence trends for these groups. Low APCA prevalence in older male smokers may explain the lack of a cancer association in this setting. Stronger associations in H. pylori seronegative individuals supports our hypothesis of autoimmune gastritis replacing H. pylori as the driving factor for the unexpected increases of gastric cancer in certain populations. APCA has potential utility as a predictor of gastric cancer risk, but AIFA may be too rare for clinical application in asymptomatic individuals.

Citation Format: Minkyo Song, M. Constanza Camargo, Hormuzd A. Katki, Stephanie J. Weinstein, Demetrius Albanes, Heljä-Marja Surcel, Charles S. Rabkin. Associations of anti-parietal cell and anti-intrinsic factor antibodies with gastric cancer risk [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1053.