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Genotoxicity in Patients on Long-term Proton Pump Inhibitor Therapy in Korea: A Nested Case-control, Prospective, Pilot Study

최윤이 ( Choi Youn-I ) - Gachon University Gil Medical Center Department of Internal Medicine

정준원 ( Chung Jun-Won ) - Gachon University Gil Medical Center Department of Internal Medicine
박동균 ( Park Dong-Kyun ) - Gachon University Gil Medical Center Department of Internal Medicine
김경오 ( Kim Kyoung-Oh ) - Gachon University Gil Medical Center Department of Internal Medicine
권광안 ( Kwon Kwang-An ) - Gachon University Gil Medical Center Department of Internal Medicine
김윤재 ( Kim Yoon-Jae ) - Gachon University Gil Medical Center Department of Internal Medicine
 ( Kim Su-Young ) - Yonsei University Wonju College of Medicine Department of Internal Medicine
 ( Ahn Sung-Min ) - Gachon University College of Medicine Gil Medical Center Department of Internal Medicine
 ( Han Mun-Deok ) - Bio Research Complex Co. Ltd.
고광필 ( Ko Kwang-Pil ) - Gachon University College of Medicine Department of Preventive Medicine

Abstract


Background/Aims: Although proton pump inhibitors (PPIs) remain a mainstay for the suppression of gastric acid secretion, long-term PPI use is associated with side effects. However, the genotoxicity associated with long-term PPI use is unclear.

Materials and Methods: This prospective observational pilot study enrolled patients who had been on PPIs for >1 year and healthy controls from July 2015 to August 2016. The subjects completed self-report questionnaires pertaining to their drug and medical history, and only those with no medical history and a ≥2-year wash-out period (for drugs other than PPIs) were included. We collected peripheral-blood lymphocytes from long-term PPI users and healthy controls and analyzed the genotoxicity by using the cytokinesis-block micronucleus cytome assay; we also determined the fasting serum levels of pyridoxine, folate, cobalamin, and homocysteine.

Results: Ten long-term PPI users and 40 healthy control subjects were enrolled. The median serum pyridoxine, folate, cobalamin, and homocysteine levels were not significantly different between the groups. The median frequencies of micronuclei (MNi), nucleoplasmic bridges (NPBs), and nuclear buds (Nbuds) per 1,000 binucleated cells, in long-term PPI users and healthy controls, were 30.3 and 16.3 (P<0.005), 2.5 and 1.8 (P<0.005), and 9.3 and 5.0 (P<0.005), respectively. Even after adjustment for confounding factors, the OR of the MNi, NPBs, and Nbuds for long-term PPI users compared with healthy control subjects were 14.1 (P<0.001), 2.0 (P=0.001), and 1.3 (P=0.3), respectively.

Conclusions: Long-term PPI use was significantly associated with an increased risk of genotoxicity after adjustment for age, sex, body mass index, medical history, drug history, and the serum levels of vitamins.

키워드

Genotoxicity test; Prospective study; Proton pump inhibitors
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