1. The Impacts of Genetic and Environmental Factors on the Progression of Chronic Pancreatitis
- Author
-
Liang-Hao Hu, Sheng-Yong Wu, Zhao-Shen Li, Yu Cao, Xiao-Nan Xu, Nan Ru, Jia-Hui Zhu, Jun Pan, Wen-Bin Zou, Yang-Yang Qian, and Zhuan Liao
- Subjects
Male ,Oncology ,medicine.medical_specialty ,Gene mutation ,Risk Factors ,Pancreatitis, Chronic ,Internal medicine ,Genotype ,medicine ,Humans ,Cumulative incidence ,Prospective Studies ,Prospective cohort study ,Survival analysis ,Hepatology ,business.industry ,Hazard ratio ,Gastroenterology ,Pancreatic Diseases ,medicine.disease ,Trypsin Inhibitor, Kazal Pancreatic ,Mutation ,Pancreatitis ,Exocrine Pancreatic Insufficiency ,business ,Alcohol consumption - Abstract
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.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.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.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 (ClinicalTrials.gov: NCT04574297).
- Published
- 2022