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

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation Pub Date : 2024-04-14 DOI:10.1111/eci.14213

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

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引用次数: 0

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.

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ABCG8 多态性会增加普通人群患胆囊癌的风险和波兰肥胖患者患胆结石的风险

背景胆石症（GD）很常见，但大多数情况下没有症状。然而，胆结石可导致胆总管结石或胆囊癌等并发症。在这项研究中，我们分析了波兰胆结石和胆囊癌患者中常见的 GD 遗传风险因素--固醇转运体 ABCG8 中的 p.D19H 变异：方法前瞻性地招募了三个成人组群：65 名胆囊癌患者、170 名计划接受减肥手术的肥胖者和 72 名因复发性胆总管结石而接受内镜逆行胰胆管造影术的患者。对照组包括 172 名无胆石症的成年人。结果与对照组（MAF = 4.0%）相比，胆结石或胆囊癌病例（MAF = 8.4%）中ABCG8 p.D19H（rs11887534）多态性的小等位基因频率（MAF）显著较高（p = .02）。胆囊癌患者（18.5%）和肥胖的 GD 患者（17.5%）的风险等位基因频率最高，其次是胆总管结石患者（13.9%）。值得注意的是，p.19结论 ABCG8 p.D19H 常见风险变异增加了中欧人患胆囊癌的风险，并增加了肥胖者患胆结石的风险。p.D19H变异体携带者可能会从个性化的预防策略中受益，尤其是在胆囊癌方面。

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来源期刊

European Journal of Clinical Investigation 医学-医学：内科

CiteScore

9.50

自引率

3.60%

发文量

192

审稿时长

1 months

期刊介绍： EJCI considers any original contribution from the most sophisticated basic molecular sciences to applied clinical and translational research and evidence-based medicine across a broad range of subspecialties. The EJCI publishes reports of high-quality research that pertain to the genetic, molecular, cellular, or physiological basis of human biology and disease, as well as research that addresses prevalence, diagnosis, course, treatment, and prevention of disease. We are primarily interested in studies directly pertinent to humans, but submission of robust in vitro and animal work is also encouraged. Interdisciplinary work and research using innovative methods and combinations of laboratory, clinical, and epidemiological methodologies and techniques is of great interest to the journal. Several categories of manuscripts (for detailed description see below) are considered: editorials, original articles (also including randomized clinical trials, systematic reviews and meta-analyses), reviews (narrative reviews), opinion articles (including debates, perspectives and commentaries); and letters to the Editor.