Serum Pepsinogen as a Biomarker for Gastric Cancer in the United States: A Nested Case-Control Study Using the PLCO Cancer Screening Trial Data.

Authors

In H, Sarkar S, Ward J, Friedmann P, Parides M, Yang J, Epplein M

Affiliations

• Montefiore Medical Center/Albert Einstein College of Medicine, Department of Surgery, Bronx, New York.
• Albert Einstein College of Medicine, Bronx, New York.
• Division of Gastroenterology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York.
• Department of Population Health Sciences, and Cancer Risk, Detection, and Interception Program, Duke Cancer Institute, Duke University, Durham, North Carolina.

Abstract

BACKGROUND: Gastric cancer (GC) lacks specific symptoms, resulting in diagnosis at later stages and high mortality. Serum pepsinogen is a biomarker for atrophic gastritis, a GC precursor, and may be useful to detect persons at increased risk of GC.

METHODS: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was conducted in the US between 1993 and 2001. ELISA-based pepsinogen tests were conducted on prediagnostic serum samples of 105 PLCO participants who developed GC and 209 age, sex, and race-matched controls. Pepsinogen positive (PG+) was defined as pepsinogen I {less than or equal to} 70μg/L and pepsinogen I/II ratio {less than or equal to} 3.0. Results of conditional logistic regression models, and sensitivity and specificity, of PG+ for GC are reported.

RESULTS: GC cases were more likely to be PG+ (31.4% vs 5.5%, p<0.001) at baseline than controls. Compared to PG-, PG+ was associated with an 8.5-fold increased risk for GC (95%CI=3.8-19.4). This risk remained significant after adjusting for Helicobacter pylori, family history of GC, education, smoking, and BMI (aOR 10.6; 95%CI=4.3-26.2). In subgroup analysis, PG+ individuals were 11-fold more like to develop non-cardia GC (OR 11.1; 95%CI=4.3-28.8); conversely, they were not significantly more likely to develop cardia GC (OR, 2.0; 95%CI=0.3-14.2). PG+ status yielded low sensitivity but high specificity for both non-cardia [44.3%; 93.6%] and cardia GC [5.7%; 97.2%].

CONCLUSIONS: Pre-diagnostic serum pepsinogen levels from a large, prospective cohort study were associated with risk of GC, particularly non-cardia GC.

IMPACT: PG status may identify individuals at higher risk of non-cardia GC for targeted screening or interventions.