Aldehyde Dehydrogenase 2 Activity Assessed Using the Acetaldehyde Breath Test Is Associated with Benign Pancreatic Disease and Pancreatic Cancer: A Case–Control Study

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Abstract
Background/Objectives: Aldehyde dehydrogenase 2 (ALDH2) detoxifies acetaldehyde, and impaired ALDH2 activity has been implicated in carcinogenesis. The acetaldehyde breath test (ABT) enables noninvasive functional assessment of ALDH2 activity, but its association with pancreatic disease remains unclear. We examined associations between ABT-assessed ALDH2 activity and pancreatic disease outcomes. Methods: This case–control study included 287 health checkup participants, 131 patients with benign pancreatic disease, and 65 patients with pancreatic cancer. Participants underwent ABT, and the acetaldehyde-to-ethanol (A/E) ratio was calculated. The ALDH2 inactive phenotype was defined as an A/E ratio ≥ 23.3. Multinomial logistic regression used health checkup participants as the reference. Results: The median A/E ratio was higher in patients with benign pancreatic disease and pancreatic cancer than in health checkup participants (21.7 and 24.2 vs. 13.6; p < 0.001). The ALDH2 inactive phenotype was associated with benign pancreatic disease (relative risk ratio [RRR], 3.55; 95% confidence interval [CI], 1.85–6.83) and pancreatic cancer (RRR, 4.82; 95% CI, 2.13–10.88). The highest A/E ratio category was also associated with benign pancreatic disease (RRR, 8.77; 95% CI, 3.59–21.39) and pancreatic cancer (RRR, 12.79; 95% CI, 4.41–37.09). Exploratory spline analyses showed associations between higher A/E ratios and pancreatic disease outcomes without clear evidence of nonlinearity. Conclusions: A higher ABT-derived A/E ratio was associated with benign pancreatic disease and pancreatic cancer in this selected case–control study. Prospective studies are needed to determine whether functional assessment of aldehyde metabolism provides clinically useful information for pancreatic disease risk assessment. Trial registration number: UMIN Clinical Trials Registry (UMIN-CTR), UMIN000052609; registered 1 November 2023.

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