Lempinen Marko, Paju Annukka, Kemppainen Esko, Smura Teemu, Kylänpää Marja-Leena, Nevanlinna Heli, Stenman Jakob, Stenman Ulf-Håkan
Fourth Department of Surgery, Helsinki University Central Hospital, FI-00029 Helsinki, Finland.
Scand J Gastroenterol. 2005 Feb;40(2):225-30. doi: 10.1080/00365520510011560.
Mutations in the Kazal type 1 serine protease inhibitor (SPINK1) gene have recently been associated with chronic pancreatitis (CP), an established risk factor for pancreatic cancer. The aim of this study was to investigate the frequency of the SPINK1 gene mutations (N34S and P55S) in patients with CP, or pancreatic cancer, and in healthy subjects in Finland.
The N34S and P55S mutations were determined by PCR amplification followed by solid-phase minisequencing in 116 patients with CP and in 188 with pancreatic cancer. In patients with CP, alcohol was the aetiological factor in 87 (75%), pancreas divisum in 4 (3%), gallstones in 5 (5%) and 20 patients (17%) had an idiopathic disease; 459 healthy individuals were enrolled as controls.
The frequency of the N34S mutation was significantly higher in patients with CP (14/116, 12%) than in controls (12/459, 2.6%) (p<0.0001). There was no difference in the frequency of the P55S mutation between patients with CP (1/116, 0.9%) and controls (6/459, 1.3%). The N34S mutation was present in 9 (10%) out of 87 patients with alcoholic CP, and in 5 (25%) patients with idiopathic CP. No SPINK1 mutations were found in patients with CP caused by anatomical variations or gallstones. Among the 188 patients with a pancreatic malignant tumour, the N34S mutation was present in 7 cases (3.7%). The frequency of the N34S mutation in healthy controls in this study was significantly higher than earlier reported in other countries (p=0.03).
The SPINK1 N34S mutation was significantly associated with an increased risk of CP. The association of the N34S mutation with alcoholic CP was marginally stronger than in earlier studies, whereas in the Finnish population in general, this mutation was significantly more frequent than reported elsewhere.
卡扎尔1型丝氨酸蛋白酶抑制剂（SPINK1）基因突变最近被认为与慢性胰腺炎（CP）有关，而慢性胰腺炎是胰腺癌的既定危险因素。本研究的目的是调查芬兰慢性胰腺炎患者、胰腺癌患者及健康受试者中SPINK1基因突变（N34S和P55S）的频率。
采用聚合酶链反应（PCR）扩增后固相微测序法，对116例慢性胰腺炎患者和188例胰腺癌患者进行N34S和P55S基因突变检测。在慢性胰腺炎患者中，87例（75%）病因是酒精，4例（3%）是胰腺分裂，5例（5%）是胆结石，20例（17%）病因不明；459名健康个体作为对照。
慢性胰腺炎患者中N34S基因突变频率（14/116，12%）显著高于对照组（12/459，2.6%）（p<0.0001）。慢性胰腺炎患者与对照组之间P55S基因突变频率无差异（慢性胰腺炎患者1/116，0.9%；对照组6/459，1.3%）。87例酒精性慢性胰腺炎患者中有9例（10%）存在N34S基因突变，20例特发性慢性胰腺炎患者中有5例（25%）存在该突变。解剖变异或胆结石所致慢性胰腺炎患者未发现SPINK1基因突变。188例胰腺恶性肿瘤患者中，7例（3.7%）存在N34S基因突变。本研究中健康对照组N34S基因突变频率显著高于其他国家先前报道的频率（p=0.03）。
SPINK1基因N34S突变与慢性胰腺炎风险增加显著相关。N34S突变与酒精性慢性胰腺炎的关联略强于早期研究，而在芬兰人群中，该突变总体上显著高于其他地方报道的频率。
