For the purpose of studying immunogenetic factors related to disease susceptibility to cervical carcinoma (squamous cell carcinoma), HLA-A,B and DR typings were performed by the standard microlymphocytotoxicity test using about 240 typing antisera in 66 Japanese patients with cervical carcinoma and 206 healthy individuals. The results obtained were as follows: 1) The patients had a significant association with HLA-Bw46 (gene frequency = 6.3%, relative risk = 3.9, p less than 0.025), compared with the controls (g.f. = 1.7%). 2) The patients had a significant association with HLA-DRw8 (g.f. = 17.3%, r.r. = 2.3, p less than 0.05), compared with the controls (g.f. = 8.9%). 3) When the patients with cervical carcinoma were divided into two groups, i.e. 53 patients with invasive carcinoma of the cervix and 13 patients with carcinoma in situ of the cervix, the former had a more significant association with both HLA-Bw46 (g.f. = 6.8%, r.r. = 4.3) and HLA-DRW8 (g.f. = 19.2%, r.r. = 2.6) than the total patients, compared with the controls. However, the latter showed only a negligible association when compared with the controls. 4) The significant linkage disequilibrium between HLA-Bw46 and HLA-DRw8 was found in the patients with cervical carcinoma (haplotype frequency = 0.059, delta = 0.047, p less than 0.002), but not in the controls (h.f. = 0.0097, delta = 0.0075). 5) On the other hand, the significant linkage disequilibrium between HLA-A2 and HLA-Bw46 was found in both the patients and the controls.

Recent results in family studies of breast cancer were overviewed. Site specific familial aggregation of the disease, with no significant increase of other cancers, by itself suggests a specified etiological role of the familial predisposition. Probably it must be interpreted by a synergism of some genetic and environmental factors. Among the cases in Cancer Institute Hospital, familially predisposed patients showed a significant differences in younger age at menarche and taller stature compared with the other patients. It has been frequently observed that a risk for the disease in the relatives of a patient is higher in pre-than in postmenopausal onset. It appears, however, that the age specific incidence rate among those women with a positive family history is consistently higher than that of the general population in any age classes except the premenopausal period. Findings obtained by recent endoclinological studies point out the concept that a possible genetic abnormality associated with the breast cancer disposition should be pertaining to the metabolism of ovarian hormone.

The relationship between gastrointestinal cancers and genetic influence was investigated. The subjects examined were 1211 cancer cases and 781 non-cancer cases registered to the 1st Department of Surgery of Kagoshima University Hospital from 1972 to 1980. The results were as follows: 1. Malignant cases were found in 266/1211 (22.0%) in the families of cancer probandus. Incidence was significantly (P less than 0.01) higher than that [130/781 (16.6%)] in those of non-cancer probandus. 2. Malignant cases were found in 79/356 (22.2%) in the families of gastric cancer probandus and in 51/189 (27.0%) in those of colo-rectal cancer probandus. 3. The relationship between cancer probandus and malignant cases in the families was classified according to the vertical relationship (grandparents-parents-uncle and aunt-probandus-children) and the horizontal relationship (probandus-siblings-cousin). 4. Incidence in the vertical relationships (159/266: 59.8%) was higher than that in the horizontal relationships (107/266: 40.2%). Incidence of the vertical relationships of female cancer probandus (gastric cancer: 70.4%, esophageal cancer: 55.7%, clorectal cancer: 73.9%) was significantly (P less than 0.05) higher than that in those of male cancer probandus. 5. Incidence of blood B type in male gastric cancer group tended to be less when compared with the control group (P less than 0.05). 6. Incidence of smoking habits in esophageal cancer group (82.2%) and the lung cancer group (63.4%) was significantly (P less than 0.01) higher than that in the control group (46.0%). 7. Incidence of drinking habits in the male esophageal cancer group (84.2%) was significantly (P less than 0.01) higher than that in the control group (53.0%).

Incidence of large bowel cancer under predominant genetic influence is estimated to occupy about one tenth of general large bowel cancer population. They are defined to include hereditary gastrointestinal polyposes (adenomatosis coli, Peutz-Jeghers syndrome and juvenile polyposis) and the non-polypotic familial (hereditary) large bowel cancer (Cancer Family Syndrome and allied conditions). The strategy for the genetic cancer high-risk group under these conditions based on the central registration system was described. Our experiences indicated the approach was actually effective for the polyposes a and was also promising for the non-polyposis familial of large bowel cancer.

Genetic factors suspected in the etiology of human hemopoietic neoplasia, such as leukemia, lymphoma and multiple myeloma, are reviewed. High incidence of consanguineous marriage was found in parents of familial leukemia in siblings. It was also noted that the age of patients with familial leukemia in children of consanguineous parents was younger than that of cases whose parents were not related. These findings suggest that genetic factors may play an important role in the etiology of familial leukemia in siblings. According to the frequencies of familial aggregations in close relatives, the genetic relationships were supposed to be important in chronic lymphocytic leukemia and acute leukemia, but not in chronic granulocytic leukemia. Increased prevalence of autoimmune diseases in relatives of leukemic patients suggests a possibility of genetic immunodeficiency as a common etiologic factor in both diseases. Immunodeficiency was found in unaffected relatives of patients with familial leukemia and lymphoma. Genetic factors were also suggested by the familial occurrences of multiple myeloma and primary macroglobulinemia, and the incidence of benign monoclonal gammopathy in relatives of patients with these diseases. HLA studies revealed the increased frequencies of A2 in acute lymphocytic leukemia, of B5 and B18 in Hodgkin's disease, and of A5 and B18 in multiple myeloma. From such relationships existing between familial immunodeficiencies and hemopoietic neoplasia, genes regulating the immune responsiveness might be involved in susceptibility to these diseases.

In human cancers, the contribution of genetic determinants is often difficult to distinguish from environmental influences. However, some cancers are inherited in Mendelian pattern, and some have closely associated with the diseases with hereditary factors. This paper reviewed characteristics of hereditary cancers, the diseases with high incidence of cancers and familial aggregation of cancers, and discussed the role of host factors in the etiology of cancer clinico-epidemiologically.