The ABCG8 polymorphism increases the risk of gallbladder cancer in the general population and gallstones in obese patients from Poland

Lukasz Krupa; Piotr Kalinowski; Joanna Ligocka; Marc Dauer; Krzysztof Jankowski; Jolanta Gozdowska; Beata Kruk; Piotr Milkiewicz; Krzysztof Zieniewicz; Marek Krawczyk; Susanne N Weber; Frank Lammert; Marcin Krawczyk

doi:10.1111/eci.14213

The ABCG8 polymorphism increases the risk of gallbladder cancer in the general population and gallstones in obese patients from Poland

Eur J Clin Invest. 2024 Apr 14:e14213. doi: 10.1111/eci.14213. Online ahead of print.

Authors

Lukasz Krupa^{1

2}, Piotr Kalinowski³, Joanna Ligocka⁴, Marc Dauer⁵, Krzysztof Jankowski^{6

7}, Jolanta Gozdowska⁸, Beata Kruk⁹, Piotr Milkiewicz^{10

11}, Krzysztof Zieniewicz³, Marek Krawczyk³, Susanne N Weber⁵, Frank Lammert¹², Marcin Krawczyk^{5

9}

Affiliations

¹ Department of Gastroenterology and Hepatology with Internal Disease Unit, Teaching Hospital No 1 in Rzeszów, Rzeszów, Poland.
² Medical Department, University of Rzeszów, Rzeszów, Poland.
³ Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
⁴ Department of Gastroenterology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
⁵ Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.
⁶ Department of Internal Medicine and Cardiology, Medical University of Warsaw, Warsaw, Poland.
⁷ Department of Social Medicine and Public Health, Medical University of Warsaw, Warsaw, Poland.
⁸ Department of Transplantation Medicine and Nephrology, Medical University of Warsaw, Warsaw, Poland.
⁹ Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
¹⁰ Translational Medicine Group, Pomeranian Medical University, Szczecin, Poland.
¹¹ Liver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland.
¹² Hannover Medical School (MHH), Hannover, Germany.

PMID: 38616505
DOI: 10.1111/eci.14213

Abstract

Background: Gallstone disease (GD) is common but remains asymptomatic in most cases. However, gallstones can lead to complications like choledocholithiasis or gallbladder cancer. In this study, we analyse the common genetic risk factor for GD, the p.D19H variant in the sterol transporter ABCG8, in Polish patients with gallstones and gallbladder cancer.

Methods: Three adult cohorts were prospectively recruited: 65 patients with gallbladder cancer, 170 obese individuals scheduled for bariatric surgery and 72 patients who underwent endoscopic retrograde cholangiopancreatography due to recurrent choledocholithiasis. The control cohort consisted of 172 gallstone-free adults. The ABCG8 p.D19H (rs11887534) polymorphism was genotyped using TaqMan assays.

Results: The minor allele frequency (MAF) of the ABCG8 p.D19H polymorphism was significantly (p = .02) higher among cases with either gallstones or gallbladder cancer (MAF = 8.4%) as compared to controls (MAF = 4.0%). The highest frequency of the risk allele was detected in patients with gallbladder cancer (18.5%) and obese patients with GD (17.5%), followed by individuals with choledocholithiasis (13.9%). Notably, the p.19H variant was associated with an increased risk of developing gallbladder cancer (OR 2.76, 95% CI 1.16-6.54, p = .01) and an increased risk of GD in obese individuals scheduled for bariatric surgery (OR = 2.70, 95% CI 1.05-6.49, p = .03), but did not significantly affect the risk of choledocholithiasis.

Conclusions: The ABCG8 p.D19H common risk variant increases the risk of developing gallbladder cancer in Central Europeans and enhances the risk of gallstones in the obese. Carriers of the p.D19H variant might benefit from personalized preventive strategies, particularly regarding gallbladder cancer.

Keywords: ABCG8 polymorphism; cholesterol; gallbladder; genetic risk; hepatobiliary tumours; obesity.

Abstract

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