Ru Nan, Wu Sheng-Yong, Wang Lei, Zhu Jia-Hui, Xu Xiao-Nan, Guo Ji-Yao, Hu Liang-Hao, Li Zhao-Shen, Zou Wen-Bin, Liao Zhuan
Department of Gastroenterology, Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China; Shanghai Institute of Pancreatic Diseases, Shanghai, China.
Department of Health Statistics, Naval Medical University, Shanghai, China.
Pancreatology. 2021 Aug;21(5):848-853. doi: 10.1016/j.pan.2021.05.304. Epub 2021 Jun 5.
The relationship between SPINK1 and pancreatic cancer (PC) remains controversial. The current study aimed to determine the effect of SPINK1 mutations on PC development among patients with chronic pancreatitis (CP).
This is a prospective observational study including a large cohort of 965 CP patients with 11-year follow-up. Patients' demographic characteristics and clinical CP outcomes were documented in detail. Genetic testing was performed. The effect of SPINK1 mutations on the clinical development of PC was explored using Cox proportional hazards regression. Subgroup analyses conducted included the consideration of gender, onset age of CP (early- and late-onset), etiologies of CP, smoking, and alcoholic drinking status.
PC was diagnosed in 2.5% (24/965) of patients, and the cumulative incidence rates were 0.2%, 0.8%, and 1.5% at 3, 5, and 10 years since the onset of CP, respectively. In this cohort, SPINK1 c.194+2T > C was the most common variant with a proportion of 39.1%. And the risk of PC development varied marginally between patients with and without SPINK1 mutations (Cox HR 0.39(0.14-1.04), P = 0.059). In the subgroup analyses, patients carrying SPINK1 mutations had a significantly lower risk of PC (Cox HR 0.18(0.04-0.80), P = 0.025) in the non-smoking group. SPINK1 mutations showed no significant effect in the other subgroups considered.
CP patients harboring SPINK1 mutations do not have an elevated risk of PC development compared to mutation-negative CP patients. On the contrary, SPINK1 mutations may be a protective factor in non-smoking patients with CP.
丝氨酸蛋白酶抑制剂Kazal型1（SPINK1）与胰腺癌（PC）之间的关系仍存在争议。本研究旨在确定SPINK1突变对慢性胰腺炎（CP）患者PC发生发展的影响。
这是一项前瞻性观察性研究，纳入了965例CP患者的大型队列，并进行了11年的随访。详细记录了患者的人口统计学特征和CP的临床结局。进行了基因检测。使用Cox比例风险回归探讨SPINK1突变对PC临床发展的影响。进行的亚组分析包括考虑性别、CP发病年龄（早发和晚发）、CP病因、吸烟和饮酒状况。
2.5%（24/965）的患者被诊断为PC，自CP发病起3年、5年和10年的累积发病率分别为0.2%、0.8%和1.5%。在该队列中，SPINK1基因c.194+2T>C是最常见的变异，比例为39.1%。有和没有SPINK1突变的患者发生PC的风险略有差异（Cox风险比0.39（0.14 - 1.04），P = 0.059）。在亚组分析中，非吸烟组中携带SPINK1突变的患者发生PC的风险显著较低（Cox风险比0.18（0.04 - 0.80），P = 0.025）。在其他考虑的亚组中，SPINK1突变未显示出显著影响。
与SPINK1突变阴性的CP患者相比，携带SPINK1突变的CP患者发生PC的风险并未升高。相反，SPINK1突变可能是CP非吸烟患者的一个保护因素。
