Hayashi Naoko, Egami Hiroshi, Ogawa Michio
Department of Surgery II, Kumamoto University Medical School, Kumamoto, Japan.
Nihon Geka Gakkai Zasshi. 2002 Jun;103(6):476-81.
Pancreatic cancer is an important cause of death from cancer throughout the world. Until recently, pancreatic cancer was a poorly understood disease. Research in the past decade has shown conclusively, however, that pancreatic cancer is primarily genetic in nature. Inactivation with a variety of tumor-suppressor genes such as p53, p16, and DPC4, and genome-maintenance genes such as BRCA2, coupled with the activation of oncogenes such as K-ras, are a few of the mutations that trigger the growth of cancerous cells. The genetic profile of pancreatic cancer has reshaped the nomenclature describing histological progression in pancreatic ductal tumorigenesis. K-ras mutations frequently occur early, whereas changes in the expression and genetic integrity of the p16 gene appear in intermediate lesions, and the inactivation of the p53 and DPC4 genes and activation of telomerase occur late in the neoplastic progression. Although the majority of pancreatic cancers occur sporadically, a minority has been shown to aggregate in families and has aided our understanding of pancreatic tumorigenesis. An improved understanding of the genetics of pancreatic cancer should lead to the development of gene-based screening tests and novel rational therapies.
胰腺癌是全球癌症死亡的一个重要原因。直到最近，胰腺癌仍是一种了解甚少的疾病。然而，过去十年的研究确凿地表明，胰腺癌本质上主要是遗传性的。多种肿瘤抑制基因（如p53、p16和DPC4）以及基因组维护基因（如BRCA2）的失活，再加上癌基因（如K-ras）的激活，是引发癌细胞生长的一些突变。胰腺癌的基因特征重塑了描述胰腺导管肿瘤发生组织学进展的命名法。K-ras突变通常早期发生，而p16基因的表达和基因完整性变化出现在中间病变中，p53和DPC4基因的失活以及端粒酶的激活则发生在肿瘤进展的后期。虽然大多数胰腺癌是散发性的，但少数已被证明在家族中聚集，这有助于我们对胰腺肿瘤发生的理解。对胰腺癌遗传学的更好理解应会导致基于基因的筛查测试和新型合理疗法的开发。
