Miyashita Yohei, Hitsumoto Tatsuro, Fukuda Hiroki, Kim Jiyoong, Ito Shin, Kimoto Naoki, Asakura Koko, Yata Yutaka, Yabumoto Masami, Washio Takashi, Kitakaze Masafumi
Department of Legal Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan.
Department of Clinical Research and Development, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, Japan.
EClinicalMedicine. 2023 Dec 12;67:102353. doi: 10.1016/j.eclinm.2023.102353. eCollection 2024 Jan.
Although previous studies have showed that metabolic syndrome is one of the contributors of pancreatic cancer, there is no clear consensus that early stages of metabolic syndrome are linked to increased incidence of pancreatic cancer. Therefore, we confirmed the linkage between metabolic syndrome and pancreatic cancer, and shown that even early stage of metabolic syndrome is linked to pancreatic cancer in the retrospective observational study.
We recruited approximately 4.6 million Japanese in 2005 and followed up these subjects for more than 10 years. At the time of the enrollment, after obtaining clinical data with prescribed drugs and examining the presence or absence of metabolic syndrome (MetS), we followed up on these subjects with and without MetS to examine the incidence of pancreatic cancer. The modified criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATPIII) were used to define MetS.
During the 40.7-month average follow-up period for 2,707,296 subjects with complete data for identifying MetS and important risk factors without pancreatic cancer before the enrollment, 87,857 suffered from pancreatic cancer. Pancreatic cancers occurred in 16,154 of 331,229 subjects (4.9%) in the MetS group and 71,703 of 2,376,067 patients (3.0%) in the non-MetS group (hazard ratio (HR), 1.37; 95% confidence interval [CI], 1.34-1.39; p < 0.0001 after the adjustment with age, smoking and sex). As the number of the constituent factors of MetS increased from one to five, the incidence of pancreatic cancer correspondingly increased (HR: 1.11, 1.23, 1.42, 1.66 and 2.03 using Cox proportional hazard models, p < 0.0001 each). When we defined MetS using the Japanese criteria, the results are in accord with the results using NCEP/ATPIII. Especially pre-metabolic syndrome (pre-MetS) in the Japanese criteria was tightly linked to the incidence of pancreatic cancers.
MetS is confirmed to be linked to pancreatic cancer. Although we cannot conclude causality. We also demonstrated the link between pre-MetS and pancreatic cancer.
The sponsors of the study were Japanese Heart Foundation and Japan Cardiovascular Research Foundation. This is also partially supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan; and Grants-in-Aid from the Japan Agency for Medical Research and Development.
尽管先前的研究表明代谢综合征是胰腺癌的促成因素之一，但对于代谢综合征的早期阶段是否与胰腺癌发病率增加存在关联，目前尚无明确共识。因此，我们在一项回顾性观察研究中证实了代谢综合征与胰腺癌之间的联系，并表明即使是代谢综合征的早期阶段也与胰腺癌有关。
2005年我们招募了约460万日本人，并对这些受试者进行了10多年的随访。在入组时，在获取使用处方药的临床数据并检查代谢综合征（MetS）的有无后，我们对有和没有MetS的这些受试者进行随访，以检查胰腺癌的发病率。采用美国国家胆固醇教育计划成人治疗小组第三次报告（NCEP/ATPIII）的修订标准来定义MetS。
在对2707296名在入组前没有胰腺癌且有完整数据用于确定MetS和重要危险因素的受试者进行的平均40.7个月的随访期内，有87857人患胰腺癌。在MetS组的331229名受试者中有16154人（4.9%）发生胰腺癌，在非MetS组的2376067名患者中有71703人（3.0%）发生胰腺癌（风险比（HR）为1.37；95%置信区间[CI]为1.34 - 1.39；在对年龄、吸烟和性别进行调整后，p < 0.0001）。随着MetS构成因素的数量从1个增加到5个，胰腺癌的发病率相应增加（使用Cox比例风险模型的HR分别为1.11、1.23、1.42、1.66和2.03，各p < 0.0001）。当我们使用日本标准定义MetS时，结果与使用NCEP/ATPIII的结果一致。特别是日本标准中的代谢综合征前期（pre - MetS）与胰腺癌的发病率紧密相关。
已证实MetS与胰腺癌有关。尽管我们不能得出因果关系。我们还证明了pre - MetS与胰腺癌之间的联系。
该研究的资助者是日本心脏基金会和日本心血管研究基金会。这也部分得到了日本文部科学省的资助；以及日本医疗研究与开发机构的资助。
