Serum pepsinogens and risk of esophageal squamous dysplasia

Abstract

Pepsinogens are a class of endopeptidases that are secreted by the gastric epithelium and released into the circulation. Low serum pepsinogen I (PGI) and low serum pepsinogen I/pepsinogen II ratio (PGI/II ratio) are markers of gastric fundic atrophy, and have recently been shown to be associated with increased risk of esophageal squamous cell carcinoma (ESCC). We conducted the current study to test whether these markers are also associated with esophageal squamous dysplasia (ESD), the precursor lesion of ESCC. We measured serum PGI and PGII, using enzymelinked immunosorbent assays, in 125 case subjects (patients with moderate or severe ESD) and 250 sex-matched control subjects (no ESD) selected from an endoscopic screening study in Linxian, China. We used conditional logistic regression models adjusted for age, smoking and place of residence to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Serum PGI showed no statistically significant association with ESD, whether analyzed as a dichotomous, ordinal (quartiles) or continuous variable. Lower serum PGI/II ratio, however, showed a dose-response association with increased risk of ESD, with an adjusted OR (95% CI) of 2.12 (1.08-4.18), comparing the lowest versus the highest quartile. The association between the lower serum PGI/II ratio and log OR of ESD was nearly linear, and the p-value for the continuous association was 0.03. Lower serum PGI/II ratio was linearly associated with higher risk of ESD. This result is consistent with recent findings that gastric atrophy may increase the risk of ESCC. Published 2008 Wiley-Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.Key words: esophageal cancer; squamous dysplasia; pepsinogen; China Pepsinogen I (PGI) and pepsinogen II (PGII) are 2 classes of endopeptidases that are secreted by the gastric epithelium and can hydrolyze peptides in acid environments. 1 Some of the secreted molecules are released into the circulation and can be measured as serum PGI and serum PGII.Serum pepsinogen levels have been used as markers of gastric fundic atrophy. 2,3 As this atrophy progresses, serum PGI levels are reduced but serum PGII levels remain stable or are increased, which results in lower PGI levels and a lower serum pepsinogen I/ pepsinogen II ratio (PGI/II ratio). 3 Both low serum PGI and low serum PGI/II ratio have been used as markers for gastric fundic atrophy. 2,3 However, low serum PGI/II is usually a more accurate marker for this atrophy than PGI alone. 3 Serum pepsinogens can also predict gastric cancer risk. A large number of epidemiologic studies have shown that atrophy of gastric fundic mucosa, diagnosed histologically or by measuring serum pepsinogens, is associated with higher risk of gastric cancer. [4][5][6][7][8][9][10][11][12][13][14][15][16] Like the association with atrophy, some studies have suggested that the serum PGI/II ratio may be a stronger risk predictor of future gastric cancer risk than serum PGI alone. 5,10,11 The ...

Serum pepsinogens and risk of gastric and oesophageal cancers in the General Population Nutrition Intervention Trial cohort

“…Previous studies have also found similar strong correlation coefficients between PGI and PGII,3 9 30 perhaps because both peptides are secreted by the fundic cells of the stomach. These findings are consistent with the hypothesis that the PGI/II ratio takes into account both the fact of fundic atrophy (via the PGI component) and the total secretion capacity of pepsinogens in an individual (via the PGII component).…”

Association between Upper Digestive Tract Microbiota and Cancer-Predisposing States in the Esophagus and Stomach

“…Some previous studies suggest that chronic atrophic gastritis, defined by a low serum PGI/II ratio, is associated with risk of both ESD and ESCC (13–16). A study using the same Chinese cohort that is evaluated in the current analysis also showed that lower serum PGI/II was associated with increased risk of ESD (17), but a prospective study in the same population failed to find such an association with ESCC (9). …”

Helicobacter pylori infection and fundic gastric atrophy are not associated with esophageal squamous cell carcinoma

“…Recent studies from Asia and Northern Europe suggest that FGA may also be associated with an increased risk for developing OSCC [15][16][17][18]. However, a large case-cohort study conducted in the People's Republic of China with over 15 years of follow-up did not support this association [19].…”

“…In 2004, Ye et al [17] first reported an association between FGA diagnosed by serology and an increased risk for OSCC in a case-control study conducted in the native Swedish population [17]. Further, case-control studies from Japan and China have reported similar data [15,16]. Bacterial overgrowth due to reduced acid secretion in patients with FGA has been proposed as a possible causal mechanism.…”