Tamura Kazuo, Utsunomiya Joji, Iwama Takeo, Furuyama Jun-ichi, Takagawa Tetsuya, Takeda Naohisa, Fukuda Yoshihiro, Matsumoto Takayuki, Nishigami Takashi, Kusuhara Kiyoshi, Sagayama Ken, Nakagawa Kazuhiko, Yamamura Takehira
Laboratory of Hereditary Tumor, Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1 Mukogawa-cho, 663-8501, Nishinomiya, Japan.
Int J Clin Oncol. 2004 Aug;9(4):232-45. doi: 10.1007/s10147-004-0430-4.
It is thought that malignant tumors occur through interactions of multiple environmental factors and a personal genetic factor. A normal somatic cell having an intrinsic function is able to acquire the characteristics of a malignant cell under the influence of many factors. A small percentage of all tumors have obvious familial aggregation. These entities are called familial cancer. The familial cancer syndrome is well defined for colorectal cancer, breast cancer, endocrine neoplasia, and so on. Traits of familial tumors are sequentially inherited by offspring through gametes in a Mendelian fashion, most commonly in an autosomal-dominant manner. Carcinogenesis requires multiple genetic events. A patient with a familial tumor is ahead of an individual without any germline mutation in the carcinogenesis process. In such a situation, patients frequently suffer from multiple malignant tumors at a young age. It is well known that three major genes are closely related to the cell cycle and tumorigenesis. These gene types are protooncogenes, tumor suppressor genes, and DNA mismatch repair genes. Proto-oncogenes function to accelerate cells during the G1 or growth phase of the cell cycle. Tumor suppressor genes act as blocks against cell growth and proliferation. Inactivation of tumor suppressor genes requires alterations in both alleles. These phenomena are known as Knudson's two-hits theory. However, DNA mismatch repair genes are known as caretaker genes and correct mismatch pair generation during DNA replication. Germline mutation of DNA mismatch repair genes causes hereditary nonpolyposis colorectal cancer. The tumor phenotype from patients with hereditary nonpolyposis colorectal cancer is demonstrated to be microsatellite instability positive.
人们认为恶性肿瘤是通过多种环境因素与个人遗传因素相互作用而发生的。具有内在功能的正常体细胞在多种因素的影响下能够获得恶性细胞的特征。所有肿瘤中有一小部分具有明显的家族聚集性。这些实体被称为家族性癌症。家族性癌症综合征在结直肠癌、乳腺癌、内分泌肿瘤等方面有明确的定义。家族性肿瘤的性状以孟德尔方式通过配子依次遗传给后代，最常见的是常染色体显性方式。肿瘤发生需要多个基因事件。患有家族性肿瘤的患者在肿瘤发生过程中比没有任何种系突变的个体更具优势。在这种情况下，患者经常在年轻时患多种恶性肿瘤。众所周知，有三种主要基因与细胞周期和肿瘤发生密切相关。这些基因类型是原癌基因、肿瘤抑制基因和DNA错配修复基因。原癌基因在细胞周期的G1期或生长阶段发挥加速细胞的作用。肿瘤抑制基因起到阻止细胞生长和增殖的作用。肿瘤抑制基因的失活需要两个等位基因都发生改变。这些现象被称为克努森的双击理论。然而，DNA错配修复基因被称为守护者基因，在DNA复制过程中纠正错配碱基对的产生。DNA错配修复基因的种系突变会导致遗传性非息肉病性结直肠癌。遗传性非息肉病性结直肠癌患者的肿瘤表型被证明是微卫星不稳定阳性。
