The Impacts of Genetic and Environmental Factors on the Progression of Chronic Pancreatitis

Nan Ru; Xiao-Nan Xu; Yu Cao; Jia-Hui Zhu; Liang-Hao Hu; Sheng-Yong Wu; Yang-Yang Qian; Jun Pan; Wen-Bin Zou; Zhao-Shen Li; Zhuan Liao

doi:10.1016/j.cgh.2021.08.033

The Impacts of Genetic and Environmental Factors on the Progression of Chronic Pancreatitis

Clin Gastroenterol Hepatol. 2022 Jun;20(6):e1378-e1387. doi: 10.1016/j.cgh.2021.08.033. Epub 2021 Aug 28.

Authors

Nan Ru¹, Xiao-Nan Xu², Yu Cao³, Jia-Hui Zhu³, Liang-Hao Hu³, Sheng-Yong Wu⁴, Yang-Yang Qian², Jun Pan², Wen-Bin Zou⁵, Zhao-Shen Li³, Zhuan Liao⁶

Affiliations

¹ Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China; Shanghai Institute of Pancreatic Diseases, Shanghai, China; Department of Gastroenterology, 987th Hospital of the Joint Logistics Support Force of the People's Liberation Army, Baoji, Shaanxi, China.
² Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China.
³ Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China; Shanghai Institute of Pancreatic Diseases, Shanghai, China.
⁴ Department of Health Statistics, Naval Medical University, Shanghai, China.
⁵ Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China; Shanghai Institute of Pancreatic Diseases, Shanghai, China. Electronic address: dr.wenbinzou@hotmail.com.
⁶ Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China; Shanghai Institute of Pancreatic Diseases, Shanghai, China. Electronic address: zhuanleo@126.com.

PMID: 34461303
DOI: 10.1016/j.cgh.2021.08.033

Abstract

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 (ClinicalTrials.gov: NCT04574297).

Keywords: Alcohol Consumption; Chronic Pancreatitis; Gene Mutations; Pancreatic Insufficiency; Smoking.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Exocrine Pancreatic Insufficiency* / genetics
Humans
Male
Mutation
Pancreatic Diseases* / complications
Pancreatitis, Chronic* / complications
Pancreatitis, Chronic* / epidemiology
Pancreatitis, Chronic* / genetics
Prospective Studies
Risk Factors
Trypsin Inhibitor, Kazal Pancreatic / genetics

Substances

SPINK1 protein, human
Trypsin Inhibitor, Kazal Pancreatic

Associated data

ClinicalTrials.gov/NCT04574297