Abstract
It is thought that malignant tumors occur through interactions of multiple environmental factors and personal genetic factors. 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 sequentially inherit to 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.
On the other hand, we recognize that 10％ – 30％ of malignant diseases are polygenic or multifactorial disorders. Candidate genes involved in these entities have characteristics of low-penetrance and high frequency in the population. Therefore, findings and information with regard to low-penetrance genes may provide great benefit to cancer prevention, adding the stratification by a lot of environmental factors. We should recognize the importance of low-penetrance genes, and should synthetically investigate environmental and genetic factors. （The contents of this article were presented in the third international symposium of Institute for Advanced Medical Sciences, Hyogo College of Medicine. Also, the details regarding the concept of familial cancer were already published in the official journals of the Japan Society of Clinical Oncology; Int. J. Clin. Oncol. 9: 232–245, 2004. Because the importance of familial cancer study has been recognized from the past and is unchangeable in future, I think that it is necessary for the implications to be made known to many members of The Japanese Society for Familial Tumors. Therefore, I describe the same purport repeatedly. In addition single gene disorders, I now advocate the necessity of studying low-penetrance genes, which are involved in cancer-induction and/or cancer-promotion）
