title: Mechanism of carcinogenesis in familial tumors.
abstract: 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.
authors.affiliation: Laboratory of Hereditary Tumor, Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1 Mukogawa-cho, 663-8501, Nishinomiya, Japan. kzotmr@hyo-med.ac.jp
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tamura
authors.forename: Joji
authors.initials: J
authors.lastname: Utsunomiya
authors.forename: Takeo
authors.initials: T
authors.lastname: Iwama
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Furuyama
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takagawa
authors.forename: Naohisa
authors.initials: N
authors.lastname: Takeda
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fukuda
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishigami
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kusuhara
authors.forename: Ken
authors.initials: K
authors.lastname: Sagayama
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Takehira
authors.initials: T
authors.lastname: Yamamura
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D011519:Proto-Oncogenes / Q000235:genetics