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Association of Autoantibodies to Gastric Mucosa and Risk of Gastric Cancer


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In a case-control study reported in JAMA Oncology, Minkyo Song, MD, PhD, and colleagues found that seropositivity for gastric antiparietal cell antibodies (APCAs) was associated with an increased risk of gastric cancer among younger Finnish women who were seronegative for antibodies to Helicobacter pylori.

As stated by the investigators, “Autoimmune gastritis is an alternative cause of gastric carcinogenesis. This cause may be gaining importance with declining prevalence of chronic H pylori infection.”

Minkyo Song, MD, PhD

Minkyo Song, MD, PhD

Study Details

The study involved 529 case-control matched pairs of Finnish women of reproductive age (from the Finnish Maternity Cohort [FMC]; born between 1938 and 1989) and 457 matched pairs of older Finnish men (from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention [ATBC] Study; born between 1916 and 1939).

The mean participant ages were 30.5 years in the FMC cohort and 57.5 years in the ATBC cohort, with median time from baseline to diagnosis among cases of 17 years and 11 years, respectively. APCAs, anti–intrinsic factor antibodies (AIFAs), and anti–H pylori antibodies were measured in baseline serum.

Key Findings

Among the 529 female cases and controls in the FMC cohort, baseline H pylori seroprevalence was 74.5% (n = 394) among cases vs 27.6% (n = 146) among controls. The odds ratio (OR) for the association of H pylori seropositivity with cancer risk was 7.38 (95% confidence interval [CI] = 5.28–10.31).

Baseline APCA seropositivity was 17.6% among cases (n = 93) vs 10% (n = 53) among controls, with an odds ratio of 1.85 (95% CI = 1.30–2.64). In analysis stratified by H pylori serostatus, the association between APCA seropositivity and cancer risk was significantly stronger among H pylori–seronegative women (OR = 5.52, 95% CI = 3.16–9.64) vs H pylori–seropositive women (OR = 1.29, 95% CI = 0.64–2.60, P = .002 for interaction). 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).

Among the 457 male cases and controls in the ATBC cohort, baseline H pylori seroprevalence was 87.3% (n = 399) among cases vs 72.0% (n = 329) among controls. The odds ratio for the association of H pylori seropositivity with cancer risk was 2.81 (95% CI = 1.95–4.06). Baseline APCA seropositivity was 7.2% (n = 33) among cases vs 7.7% (n = 35) among controls (OR = 0.98, 95% CI = 0.60–1.62), with no significant associations with H pylori seronegative status (OR = 0.99, 95% CI = 0.32–3.04) or seropositive status (OR = 1.06, 95% CI = 0.60–1.88).

In both cohorts, baseline AIFA seroprevalence was < 2% among both cases and controls, with no significant associations with cancer risk being observed overall or according to H pylori serostatus.

The investigators concluded, “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.”

Dr. Song, of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was supported by the Intramural Research Program of the National Cancer Institute. For full disclosures of the study authors, visit jamanetwork.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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