The Impacts of Genetic and Environmental Factors on the Progression of Chronic Pancreatitis
The Impacts of Genetic and Environmental Factors on the Progression of Chronic Pancreatitis
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遗传和环境因素对慢性胰腺炎进展的影响
DOI：
10.1016/j.cgh.2021.08.033
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发表时间：
2022-05-02
影响因子：
12.6
通讯作者：
Liao, Zhuan
中科院分区：
文献类型：
--
作者：
Ru, Nan;Xu, Xiao-Nan;Liao, Zhuan
背景与目的：环境因素，如饮酒和吸烟，以及遗传因素都与慢性胰腺炎(CP)的发病风险密切相关。然而，它们对CP进展的影响仍然缺乏全面的了解。方法：对大量具有已知遗传背景的CP患者进行前瞻性队列研究。应用Kaplan-Meier生存曲线分析CP发病后胰腺功能不全的累积发生率。多因素COX比例风险回归分析。结果：共798例患者进入研究，随访10.5年。在410例(51.4%)患者中发现了SPINK1、PRSS1、CTRC或CFTR基因罕见的致病基因。在基因突变阳性组(P<；.001)和基因突变阴性组(P=.001)中，有吸烟史和/或饮酒史的患者发生胰腺功能不全的时间明显较早。然而，尽管有酒精和/或吸烟，有基因突变和无基因突变的患者发生胰腺功能不全的情况没有显著差异，P值分别为0.064和0.115。多因素COX回归分析显示，慢性胰腺炎的发病年龄(危险比，1.02；P<；.001)和饮酒(HR，1.86；P<；.001)是糖尿病的独立危险因素，而男性(HR，1.84；P=.022)和吸烟(HR，1.56；P=.028)是脂肪肝的预测因素。结论：虽然CP的4个主要易感基因罕见的致病基因突变与胰腺功能不全的发生无明显相关性，但环境因素(饮酒或吸烟)显著加速了疾病的进展
BACKGROUND & AIMS: Both environmental factors, such as alcohol consumption and smoking, and genetic factors are strongly associated with the risk of developing chronic pancreatitis (CP). However, comprehensive understanding of their impacts on the progression of CP remains elusive.METHODS: A prospective cohort study was performed on a large cohort of CP patients with known genetic backgrounds. The cumulative incidence of pancreatic insufficiency after the onset of CP was analyzed using Kaplan-Meier survival curves. Multivariate Cox proportional hazards regression analysis also was performed.RESULTS: A total of 798 patients were enrolled in the study and followed up for 10.5 years. Rare pathogenic genotypes in the SPINK1, PRSS1, CTRC, or CFTR genes were identified in 410 (51.4%) patients. The development of pancreatic insufficiency was significantly earlier in patients with a history of smoking and/or alcohol consumption in both the positive (P < .001) and negative (P = .001) gene mutation groups. However, the development of pancreatic insufficiency did not differ significantly between patients with and without gene mutations despite alcohol and/or smoking status, with P values of .064 and .115, respectively. Multivariate Cox regression analysis showed that age at onset of CP (hazard ratio, [HR], 1.02; P < .001) and alcohol consumption HR, 1.86; P < .001) were independent risk factors for the development of diabetes, while male sex (HR, 1.84; P = .022) and smoking (HR, 1.56; P = .028) were predictors of steatorrhea.CONCLUSIONS: Although rare pathogenic mutations in the 4 major susceptibility genes for CP were not correlated significantly with the development of pancreatic insufficiency, environmental factors (either alcohol consumption or smoking) significantly accelerated disease progression