Molecular mechanisms for inflammation-promoted pathogenesis of cancer--The Sixteenth International Symposium of the Sapporo Cancer Seminar.

Inflammation is a necessary process by which the body rejects microbial invaders. Unfortunately, in some circumstances, inflamma tion persists without attaining its foremost objective. Inflammatory cells chronically inundate an organ system and, in the process, dam age normal host cells. Virtually all clinicians recognize the link betweenchronic inflammation and cancer.Whether the underlying process be colitis, chronic skin ulceration, hepatitis, pancreatitis, cystitis, or gastritis, the long-term outcome is frequently malignancy. Although this association is well accepted, it is poorly understood. The purpose of the Sixteenth Sapporo Cancer Seminar, as set forth by Dr. H. Kobayashi (The Sapporo Cancer Seminar Foundation, Sap poro, Japan) and Dr. Hosokawa (Hokkaido University School of Medicine, Sapporo, Japan), was to dissect what is currently known about the pathogenesis of inflammation-related cancer and to set a course for future collaborative research in this multidisciplinary field. A historical context for this year's topic was introduced in the opening keynote address by Dr. T. Sugimura (National Cancer Center, Tokyo, Japan). The inflammation-malignancy link dates back to the days of Virchow. Early experiments, many of which were performed in Japan, focused on application of irritative substances to the skin of animals, imitating the observation linking coal tar to scrotal cancer in chimney sweeps. The connection between inflammation and malig nancy was ultimately brought to the forefront by Peyton Rous and others in the 20th century. It wasn't until very recently, however, that the genetic consequences of inflammation began to be recognized. Dr. Sugimura advanced the multistep carcinogenesis view that exogenous carcinogens magnify the opportunity for chronic inflammation to progress to cancer. Dr. J. Parsonnet (Stanford University, Stanford, CA) focused on the litany of infectious agents involved in carcinogenesis. These include papillomaviruses, EBV, hepatitis viruses B and C, human T-cell lymphotrophic virus I, Helicobacter pylon, Mycobacterium ulcerans, Salmonella typhi, Schistosoma hematobium and S. man soni, Opisthorchis viverrini, Clonorchis sinensis, and microbes that cause chronic osteomyelitis or cystitis. She accentuated the importance of these infections in carcinogenesis, particularly in developing countries. At present, she estimated that between one fourth and one-fifth of cancers worldwide were attributable to infection. Next to smoking, she considered infection the most important modifiable factor worldwide in determining cancer in cidence. Of interest, Dr. Parsonnet noted that germ-free animals live up to twice as long as conventional animals. She suggested that the day-to-day colonization of our bodies with normal flora comes at a considerable cost. After these introductory talks, five research themes were outlined for the program: (a) specific microbial agents linked to malignancy were described, and outlines of their putative carcinogenic mecha nisms were put forth; (b) experimental models for inflammation and cancer discussed; (c) the role of cytokines in inflammatory carcino genesis was presented; (d) the role of reactive oxygen and nitrogen