Lynch Henry T, Deters Carolyn A, Lynch Jane F, Brand Randall E
Department of Preventive Medicine and Public Health, Creighton University School of Medicine, 2500 California Plaza, Omaha, NE 68131, USA.
Fam Cancer. 2004;3(3-4):233-40. doi: 10.1007/s10689-004-9549-8.
Pancreatic cancer (PC) is the most fatal of all gastrointestinal cancers, wherein its mortality compares strikingly with its incidence. Unfortunately, 80-90% of PCs are diagnosed in the nonresectable stage. While the lifetime risk of PC in developed countries is approximately 1-3%, it is the fifth most common cause of cancer deaths among both males and females in Western countries. It occurs in excess in Jews. Approximately 5-10% of PC shows familial clustering. Examination of such familial clusters must take into consideration cancers of diverse anatomic sites, such as malignant melanoma in the familial atypical multiple melanoma (FAMMM) syndrome due to the CDKN2A (p16) germline mutation, and combinations of colorectal and endometrial carcinoma, ovarian carcinoma, and several other cancers in hereditary nonpolyposis colorectal cancer (HNPCC), which are due to mismatch repair germline mutations, the most common of which are MSH2 and MLH1 . Other hereditary disorders predisposing to PC include Peutz-Jeghers syndrome, due to the STK11 mutation, familial pancreatitis due to the cationic trypsinogen gene, site-specific familial pancreatic cancer which may be due to the 4q32-34 mutation, hereditary breast-ovarian cancer (HBOC) syndrome that is due to BRCA2 and possibly some families with HBOC that is due to BRCA1 , familial adenomatous polyposis due to the ATP gene, and ataxia telangiectasia due to the ATM germline mutation. This extant heterogeneity mandates that the physician be knowledgeable about these PC-prone syndromes which play such an important role when considering the differential diagnosis of hereditary PC. Unfortunately, there are no PC screening programs with acceptable sensitivity and specificity. However, the gold standard for screening at this time is endoscopic ultrasound. Clearly, there is a great need for the development of novel screening approaches with acceptable sensitivity and specificity. Further research is needed to elucidate those etiologic factors that contribute to the apparent excess of PC in Ashkenazi Jews. Attention should also be given to the search for mutations predisposing to PC in Jews so that opportunities to learn more about the disease's pathogenesis, as well as screening and control, may take place.
胰腺癌（PC）是所有胃肠道癌症中致死率最高的，其死亡率与发病率形成鲜明对比。不幸的是，80% - 90%的胰腺癌在不可切除阶段被诊断出来。虽然发达国家胰腺癌的终生风险约为1% - 3%，但在西方国家，它是男性和女性癌症死亡的第五大常见原因。在犹太人中发病率更高。约5% - 10%的胰腺癌呈现家族聚集性。对这类家族聚集性病例的检查必须考虑不同解剖部位的癌症，比如因CDKN2A（p16）种系突变导致的家族性非典型多发性黑色素瘤（FAMMM）综合征中的恶性黑色素瘤，以及遗传性非息肉病性结直肠癌（HNPCC）中的结直肠癌与子宫内膜癌、卵巢癌及其他几种癌症的组合，后者是由于错配修复种系突变引起的，其中最常见的是MSH2和MLH1。其他易患胰腺癌的遗传性疾病包括因STK11突变导致的黑斑息肉综合征、因阳离子胰蛋白酶原基因突变导致的家族性胰腺炎、可能因4q32 - 34突变导致的位点特异性家族性胰腺癌、因BRCA2导致的遗传性乳腺癌 - 卵巢癌（HBOC）综合征以及可能一些因BRCA1导致HBOC的家族、因ATP基因导致的家族性腺瘤性息肉病，还有因ATM种系突变导致的共济失调毛细血管扩张症。这种现有的异质性要求医生了解这些易患胰腺癌的综合征，在考虑遗传性胰腺癌的鉴别诊断时，它们起着如此重要的作用。不幸的是，目前没有具有可接受的敏感性和特异性的胰腺癌筛查项目。然而，目前筛查的金标准是内镜超声。显然，迫切需要开发具有可接受的敏感性和特异性的新型筛查方法。需要进一步研究以阐明导致阿什肯纳兹犹太人中胰腺癌明显高发的那些病因。还应关注寻找犹太人中易患胰腺癌的突变，以便有机会更多地了解该疾病的发病机制以及筛查和控制方法。
