Masamune Atsushi, Mizutamari Hiroya, Kume Kiyoshi, Asakura Tooru, Satoh Kennichi, Shimosegawa Tooru
Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Pancreas. 2004 Apr;28(3):305-10. doi: 10.1097/00006676-200404000-00018.
Mutations in the cationic trypsinogen gene are acknowledged as a risk factor for pancreatic cancer in patients with hereditary pancreatitis. However, whether patients with mutations in other genes, such as the serine protease inhibitor Kazal type 1 (SPINK1) gene, are also at a higher risk of pancreatic cancer remains unknown. We report a case of pancreatic cancer associated with chronic calcifying pancreatitis in a patient with a homozygous N34S mutation in the SPINK1 gene. A 44-year-old woman was hospitalized due to obstructive jaundice. Preoperative examination showed a tumor in the head of the pancreas and multiple pancreatic stones; pancreatoduodenectomy revealed a solid tumor, 3.0 x 2.5 cm in size, in the head of the pancreas, and numerous pancreatic stones throughout the pancreas. Pathologic studies revealed moderately differentiated tubular adenocarcinoma. Mutational analyses of the SPINK1 and PRSS1 genes in members of the patient's family were carried out. The homozygous N34S mutation in the SPINK1 gene was found in the patient and her older sister, who was previously diagnosed with chronic calcific pancreatitis and had undergone the Frey operation. The patient's parents and brother were unaffected carriers of the N34S heterozygous mutation. No family members had any mutations in the cationic trypsinogen gene. To our knowledge, this is the first reported case of chronic pancreatitis accompanied by pancreatic cancer in a patient with the SPINK1 N34S mutation. Although this case does not meet the classic criteria of hereditary pancreatitis, it does suggest that the SPINK1 N34S mutation may be associated with cancer development in patients with hereditary pancreatitis. Further prospective, multicenter trials investigating secondary screening for pancreatic cancer in hereditary pancreatitis are necessary to clarify the role of SPINK1 mutations in the development of pancreatic cancer.
阳离子胰蛋白酶原基因突变被认为是遗传性胰腺炎患者患胰腺癌的一个危险因素。然而，其他基因如丝氨酸蛋白酶抑制剂Kazal 1型（SPINK1）基因发生突变的患者是否也有更高的患胰腺癌风险仍不清楚。我们报告了1例SPINK1基因纯合N34S突变患者发生的与慢性钙化性胰腺炎相关的胰腺癌病例。一名44岁女性因梗阻性黄疸住院。术前检查显示胰头有肿瘤及多发胰石；胰十二指肠切除术显示胰头有一实性肿瘤，大小为3.0×2.5 cm，胰腺内有大量胰石。病理研究显示为中分化管状腺癌。对患者家族成员的SPINK1和PRSS1基因进行了突变分析。在患者及其姐姐中发现了SPINK1基因的纯合N34S突变，其姐姐之前被诊断为慢性钙化性胰腺炎并接受了Frey手术。患者的父母和兄弟是N34S杂合突变的未受影响携带者。家族成员中阳离子胰蛋白酶原基因均无突变。据我们所知，这是首例报道的伴有胰腺癌的慢性胰腺炎患者存在SPINK1 N34S突变的病例。虽然该病例不符合遗传性胰腺炎的经典标准，但确实提示SPINK1 N34S突变可能与遗传性胰腺炎患者的癌症发生有关。有必要进行进一步的前瞻性、多中心试验，研究遗传性胰腺炎患者胰腺癌的二级筛查，以阐明SPINK1突变在胰腺癌发生中的作用。
