Serum pepsinogens and Helicobacter pylori in relation to the risk of esophageal squamous cell carcinoma in the alpha-tocopherol, beta-carotene cancer prevention study

Abstract

Background: Helicobacter pylori can induce gastric atrophy in humans, which in turn increases gastric cancer risk. Whether H. pylori and gastric atrophy also affect the risk of esophageal squamous cell carcinoma (ESCC), however, remains unresolved.

Methods: We performed a nested case-control study within the prospective Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study to assess these relationships. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study is composed of 29,133 Finnish male smokers, ages 50 to 69 years, who were recruited during 1985-1988. Using baseline sera, we assessed H. pylori status (via immunoglobulin G antibodies against whole-cell and CagA antigens) and gastric atrophy status [via the biomarkers pepsinogen I (PGI) and pepsinogen II (PGII)] in 79 ESCC cases and 94 controls. Logistic regression with adjustment for age, date of blood draw, education, cigarette smoking, alcohol, body mass index, and fruit and vegetable intake was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI).

Results: Gastric atrophy (PGI/PGII <4) was associated with ESCC (OR, 4.58; 95% CI, 2.00-10.48). There was no evidence for an association between H. pylori and ESCC (OR, 0.94; 95% CI, 0.40-2.24).

Conclusions: These results could be explained by misclassification of H. pylori status due to serologic amnesia, ESCC risk being dependent on the functional consequences or interactions of H. pylori rather than the infection per se, gastric atrophy having a different histogenesis in ESCC without being primarily dependent on H. pylori acquisition, or a lack of statistical power to detect an effect.

Impact: Validation of these results may warrant mechanistic studies to determine the route of association between gastric atrophy and ESCC.

(c)2010 AACR.

Figures

Figure 1. The association between pepsinogen I and the risk of esophageal squamous cell carcinoma

Pepsinogen I (PGI) [μg/L] was plotted on a reverse linear scale and the odds of esophageal squamous cell carcinoma was plotted on a logarithmic scale. The vertical lines demarcate the 25th, 50th, and 75th percentiles of PGI in control subjects.

Figure 2. The association between pepsinogen II and the risk of esophageal squamous cell carcinoma

Pepsinogen II (PGII) [μg/L] was plotted on a linear scale and the odds of esophageal squamous cell carcinoma was plotted on a logarithmic scale. The vertical lines demarcate the 25th, 50th, and 75th percentiles of PGII in control subjects.

Figure 3. The association between pepsinogen I:II ratio and the risk of esophageal squamous cell carcinoma

The pepsinogen I:II ratio was plotted on a reverse linear scale and the odds of esophageal squamous cell carcinoma was plotted on a logarithmic scale. The vertical lines demarcate the 25th, 50th, and 75th percentiles of the PGI:PGII ratio in control subjects.