Recently, there has been much concern that cancer chemotherapy may have undesirable consequences in the form of secondary malignancies. At present, secondary leukemia or therapy-linked leukemia constitutes a well delineated clinical syndrome characterized by several distinct symptoms, that was illustrated by the presentation of cases recently observed. In an attempt to understand the basis for this therapy-linked leukemia, mutagenic activity of various anticancer agents were studied by the induction of sister chromatid exchanges and risk of a certain drug as a possible candidate causing secondary leukemia was discussed from the molecular cytogenetic point of view. From both clinical and cytogenetic aspects it seemed that bifunctional alkylating agents were potentially relevant to the development of secondary leukemia.

Four hundred and eight cases with multiple primary malignant neoplasms from 5,456 autopsy cases were reviewed, and their age, sex, sites and relationship between the two cancers were analysed. Expected number of the second cancer was calculated based upon the person-years of 8,444 cases with primary gastro-intestinal cancers. Significant higher incidence was observed in the oropharyngeal cancer, esophageal cancer in male, and colon cancer in female. Organ relationship was present along the gastrointestinal tract, as observed in autopsy cases. Biological meaning of multiple primary malignant neoplasms was discussed.

Same samples used in the previous paper were again analyzed by the computer system by multiple variance analysis, i.e., the quantification II (Hayashi) and logistic model. Cancer family inheritance, tobacco smoking habit and medical history were the highest risk factor groups.

To determine the gastric cancer risk factors, a case-control study was performed. Cases were the gastric cancer patients operated at NCC hospital from 1980 to 1982. Controls were the patients in Adult Disease Clinic. Main items of risk factors were cancer family inheritance tobacco smoking and alcohol drinking. Although in the case of cancer family and tobacco smoking either alone might produce gastric cancer, the syncarcinogenic type of combination of cancer family, tobacco smoking and alcohol drinking might act most definitely in gastric carcinogenesis.

Recent research support the idea that DNA damage is the initial event in the process of carcinogenesis. Involvement of DNA repair in the fixation of DNA damage leading to cancer has been suggested by the presence of several cancer-prone hereditary diseases associated with DNA repair deficiency. Among them, xeroderma pigmentosum has been most extensively investigated and the "SOS response" hypothesis, originally implied to the mechanism of mutagenesis in bacteria, appears to be an attractive hypothesis for the understanding of the cancer-proneness in xeroderma pigmentosum. The DNA repair of ionizing radiation damage, however, has not been clearly demonstrated in association with the process of radiation carcinogenesis, and further studies will be needed to understand the mechanisms of radiation carcinogenesis and the involvement of DNA repair in it.

The influence of family history, irradiation and anti-cancer drug (Mitomycin C) on the occurrence of multiple primary neoplasms was analysed using the person-year method in 1359 Japanese breast carcinoma patients. There were 111 multiple primary neoplasms, including bilateral breast cancer, in 109 patients; the incidence rate was 0.0072 per person-year. The incidence rate in patients with a family history of cancer was 1.29 times higher than in those without. In the bilateral breast cancer group there was about a 3 times higher frequency of family history of breast cancer. Irradiation therapy raised the occurrence of multiple primary neoplasms 1.28 fold, and Mitomycin C (40 mg) had no effect on the occurrence of neoplasms during a 10-year observation period.

Two cases of renal angiomyolipomas in female siblings associated with tuberous sclerosis were reported. The first case was a 47-year-old housewife who visited the hospital because of severe right flank pain. Bilateral renal angiomyolipomas and hemorrhage in the right angiomyolipoma were recognized by computerized tomography, ultrasonography and renal angiography. After 2 months she had another episode of left flank pain and was diagnosed to have hemorrhage in the left renal tumor. The pain remissed by conservative treatment. Bilateral nephrectomy and hemodialysis would be necessary if she were to have a third attack. The second case was her 36-year-old sister with the chief complaint of left flank pain and genital bleeding. CT and renal angiography suggested a large angiomyolipoma in her left kidney and a small one in her right kidney. Left nephrectomy, right partial nephrectomy and hysterectomy were performed to prevent intratumoral hemorrhage. The histopathological diagnosis was angiomyolipoma of kidneys, uterus and lymphnodes of right renal hilus. Although pre-operative differentiation of angiomyolipoma from renal cell carcinoma has been difficult, recently diagnosis has become possible by CT, ultra-sonography and angiography.

A 77-year-old male patient was admitted because of jaundice and general malaise. Exploratory laparotomy disclosed pancreatic head cancer with invasion to the intrapancreatic bile duct. Three months later, his daughter, aged 51, was admitted for evaluation because of body weight loss and back pain. CT scan disclosed 3 low-density areas in the pancreas with irregular margins and multiple low-density areas in the liver. Pancreatic cancer with liver metastasis was confirmed by autopsy. In familial pancreatic cancer, it is essential that genetic in addition to environmental factors be examined in pancreatic carcinogenesis.

The occurrence of breast cancer in 5 members of a family is reported. No specificity of the location, staging or histological typing of the lesions was observed in these cancers. But the characteristics of "hereditary breast cancer", early onset and the occurrence of metachronous double cancers, were observed. As for heredity, it is suspected to be autosomal dominant trait; on the other hand it is more appropriate to assume a poly genic pattern. Recognizing the importance of familial cancer occurrence, it may be possible to detect early cancerous lesions in family members.