INTERDISCIPLINARY PROGRAM AND COORDINATION AREA

SUMMARY OF ACTIVITIES

The Interdisciplinary Program continues to stimulate ideas through its workshops by focusing on areas in which the two countries differ greatly--in disease frequency or in approaches to research.

Workshops
A series of workshops on the role of pathologists in cancer etiology was extended during the past year by a meeting on the etiologic importance of studying cancer by subtypes. The workshop was held on October 16-17, 1984, at the East-West Center in Honolulu.
Even when cancers were classified grossly by location within an organ, important differences were noted between U.S. whites and Japanese, e.g., among whites gastric cancer most commonly affects the cardia, whereas among Japanese and Japanese-Americans it most commonly affects other parts of the stomach. Differences also were marked when other ways of subclassifying cancer were used--by tissue patterns, cytohistology, histochemistry, antigenic response, cell surface markers, ultrastructure, cell products and chemical receptors, biochemistry, cytogenetics, and studies of DNA. Cancers can be subclassified clinically by familial versus sporadic, response to therapy, and host susceptibility. Epidemiologically, cancer can be subclassified by demographic or ethnic characteristics or excessive occurrence in high-risk groups.
The workshop had three components. One concerned the organ affected: stomach, lung, lymph node, breast, and muscle (rhabdomyosarcoma). The second component concerned clinical and epidemiologic aspects: familial cancer, sub-types that have led to the mapping of cancer genes, and subtype differences between Japanese-Americans and Caucasians. The third component concerned tumor markers through which subtypes can be recognized: the use of monoclonal anti-bodies, hormones and hormone receptors, and cell atypism (of value in automated cytology). A summary of the proceedings is attached.
A workshop on adult-type cancers under 30 years of age was held in Tokyo on March 11-13, 1985. The purpose was to seek new understanding of the etiology or pathogenesis of cancer through studying its occurrence at an earlier age than usual. When the workshop was first proposed, it was judged to be of special interest to the Nakasone Program, which provided funding for additional participants from both countries. The duration was extended from the usual 2 days to 3 days.
In preparation for the workshop, participants from both countries prepared data from a variety of sources. A key source on the U.S. side was the Surveillance, Epidemiology, and End-Results (SEER) Program of the National Cancer Institute. The SEER data were remarkably filled with clusters that invite further study. The epidemic of Kaposi's sarcoma in the U.S. was detectable in 1981-82 in San Francisco, and DES-induced cancers of the lower female genital tract were apparently discernible in the data for this site. These observations lead to the belief that other clusters under age 30 within the data system may also be etiologically informative and may in some instances be due to intrauterine exposure. Among the clusters observed were 29 cancers of the lip in white males versus only four in females, 32 cancers of the gums and mouth among white females versus 13 among males, and of 31 cancers of the tongue among U.S. whites, two-thirds affected the tip, as occurs in the genetic disorder xeroderma pigmentosum. From the Japanese side came the information that there are on the average about 550 deaths annually from stomach cancer under age 30, 11 times the number of new cases diagnosed among whites in the U.S. according to the SEER data. The subtype of the cases in Japan is diffuse rather than intestinal, a surprising observation because the diffuse type was thought to have a constant rate worldwide.
The U.S. participants learned that the Japanese have a substantial number of special disease registries concerning, for example, polyps of the colon, bone cancer, soft-tissue sarcoma, xeroderma pigmentosum, melanoma, pineal tumors (which are about 12 times more frequent in Japan than elsewhere), children's cancer, and thyroid cancer. The bone cancer registry revealed a marked deficiency in the frequency of Ewing's sarcoma in Japan as compared with the U.S. The childhood cancer registry revealed that the relative frequencies differed markedly in the two countries with respect to neuroblastoma (NB), Wilms' tumor (WT), and retinoblastoma (RB). There was an excess of RB and a deficiency of WT in Japan, possibly indicating differences in susceptibility to chromosomal deletion. Possibly among the Japanese, susceptibility to deletion is greater for chromosome 13 leading to RB and less for chromosome 11, protecting against WT. In Japan among children with WT the frequency of aniridia is only half that in the U.S., which suggests that deletion of the short arm of chromosome 11 is less frequent there than among U.S. whites. Geographic abnormalities associated with other cancer have been reported by Mitelman.
The Tumor Tissue Registries at the Radiation Effects Research Foundation in Hiroshima and Nagasaki provided data which may improve in the future when ascertainment is more complete and duplications have been excluded.
The existence of a thyroid cancer registry in Japan, unknown to the U.S. participants, led them to realize that identifying information for atomic bomb survivors could be matched against that for persons listed in the registry, and thus improve estimates of the risk of thyroid cancer from radiation exposure. Overall, the list of possible studies generated by the workshop is long. A summary of the proceedings is attached.