INTERDISCIPLINARY PROGRAM AND COORDINATION AREA

SUMMARY OF ACTIVITIES

It has become our custom to focus on differences between the two countries in the frequency of certain cancers, and to try to explore them for new opportunities for research. Increasingly, exchange scientists have been selected to expand ideas that originate at these workshops.

WORKSHOPS
Cancer Epidemiology in Southeast Asia
The Interdisciplinary Program Area convened a workshop on Cancer Epidemiology in Southeast Asia, which was held in Honolulu on December 12-13, 1985. The purpose was to learn about the studies being made in Southeast Asia under the Nakasone Cancer Program, and to consider additional possibilities.
The meeting was co-organized by Dr. Kunio Aoki of Nagoya University and Dr. Robert W. Miller of NCI. It was attended by seven scientists from each country with interests in cancer epidemiology, pathology, cytogenetics, somatic cell genetics, nutrition, and virology.

The topics included:

1. Adult T-cell leukemia (HTLV-I): can it be found in Japanese forebears in SEA, who should be susceptible if comparably exposed?
   
2. Many differences described, and more yet to be reported, in cancer frequency by ethnic group- whites, blacks, Japanese and Filipinos in the United States as com-pared with one another and with Asians who did not migrate.
   
3. Diet and cancer in Korea, China and the U.S.: new improved history-taking, prospective studies and blood determinations bode well for future diet-cancer research.
   
4. Genetic susceptibility to papilloma virus and skin cancer in Japan: can it be found in Southeast Asia?
   
5. Xeroderma pigmentosum: different complementation groups in Japan than Korea.
   
6. Global differences in the frequency of hepatocellular carcinoma and its relationship to hepatitis B virus: the less mature liver at birth in Africa than in China, and both less than in the U.S. apparently explains geographic differences in the duration of risk of hepatitis B infection.
   
7. Schistosomiasis among Egyptians with urinary bladder cancer is a guide for studying the disease in Southeast Asia: search for DNA adducts, or putative mutagens in urine or carcinogenic chemicals in body fluids.
   
8. Lung cancer in Japan and Hong Kong is being compared in a case-control study.
   
9. The chromosomal pathogenesis of hydatidiform moles may be related to the high frequency of the neoplasm in Southeast Asia.
   
10. Fragile sites on chromosomes are a guide to the quality of the preparation, and may be relevant to carcinogenesis.
    
11. Previously reported geographic differences in chromosomal abnormalities in specific forms of cancer may be due to dissimilar laboratory procedures. Is the deficiency of Wilms' tumor and of the Wilms' tumor-aniridia syndrome in Japan due to resistance to chromosomal deletion of 11p-?
    

The workshop revealed that there are many opportunities for research into cancer etiology in Southeast Asia because of the differences in cancer occurrence and high-risk groups in Japan as compared with other countries in the area. It appears best to move from clinical observations to epidemiologic and laboratory research rather than to try to formulate hypotheses solely from epidemiologic observations.

Recent Advances in Bladder Cancer Research
This workshop, co-organized by Dr. Samuel M. Cohen of the University of Nebraska and Dr. Nobuyuki Ito of Nagoya City University was held in Nagoya on March 24-25, 1986, and attended by 9 U.S. participants and 18 Japanese, 8 of whom were observers. Among the information presented was the following:

1. The bladder cancer rate in Japan has been rising, but is even higher among Japanese migrants to the U.S.
   
2. An international collaboraion has revealed that the risk attributable to cigarette smoking is 50% in Boston, 30% in Japan, and in Manchester, England, is 4670 in males and 14% in females.
   
3. Occupationally, an appreciable risk of bladder cancer exists among leather workers, truck drivers, tool and dye makers, and auto/truck mechanics.
   
4. Coffee drinking is associated with a low risk of bladder cancer (1.0-1.6), which may be due to the confounding effect of cigarette smoking.
   
5. The Japanese National Autopsy Registry, 1964-68 as compared with 1982-83 revealed an apparent increase in the frequency of metastases, perhaps related to increased survival.
   
6. In human bladder cancer cells, l0-30% have activated Ha-ras gene; the neu gene was altered in 5 of 11 human bladder cancers. This report led to a proposed collaboration with another participant who is studying ornithine carboxylase in urine as a cell promoter.
   
7. The specificity of monoclonal antibodies is insufficient as yet for use in diagnosis. The potential usefulness of administering them intravesically was stressed as was the need to use multiple monoclonal antibodies.
   
8. Regulation of cell growth may be the feature in common in various areas of bladder carcinogenesis research; ie, with respect to promoting substances, growth factors, oncogenes, and electrolytes (intracytoplasmic pH, sodium, and calcium, which are important in the control of cell proliferation).
   
9. There are at least 3 classes of promoters of bladder cancer: sodium and potassium salts of certain chemicals, antioxidants, and inducers of bladder stones, such as diphenyl and uracil.
   
10. The best results of treatment in the U.S. are from a combination of cis platin and adriamycin. Chemotherapy and radiotherapy may be synergistic.
    
11. A positive reaction in a concanavalin-A agglutination assay is strongly correlated with tumor promoting activity, and may be important in the management of patients with bladder cancer.

Dr. Cohen in summarizing stated that "progress in the clinical management of human bladder cancer requires a multidisciplinary approach as evidenced by the various presentations at this meeting. In particular, new developments with monoclonal antibodies, urinary modifying factors, carcinogen exposure, and oncogenes, particularly the interaction of multiple factors, would be important in the diagnosis and treatment of the disease. Considerably more research is necessary in all of these areas, and it was suggested that a multidisciplinary and collaborative approach to the problems of clinical bladder cancer would be most productive."