Nasopharyngeal cancer, more properly called nasopharyngeal carcinoma (NPC), is most commonly found in Southern Chinese. Many people in Hong Kong know of friends and relatives who have been afflicted by this dread disease. If diagnosis is made early and treatment is given appropriately, a substantial proportion of patients can be cured, and the relapse-free survival rate can be as high as over 80 per cent within 10 years.

The Faculty of Medicine at The Chinese University of Hong Kong is a leading institution of research on the causes and treatment of various forms of cancer. And the Cancer Centre in its teaching hospital, the Prince of Wales Hospital, is so far the only centre of excellence established by the Hospital Authority to tackle problems related to cancer.

Recent work by Dr. Dolly P. Huang and her colleagues at the University's Department of Anatomical and Cellular Pathology has led to the identification of two prime suspects - chromosomes 3 and 9 - in the genetic development of NPC. This significant advance is likely to lead to improved understanding of the disease, and ultimately to better techniques of diagnosis and treatment. This project won competitive funding of $160,000 from the Research Grants Council in 1992 and an additional $566,000 for further support for two years in 1993.

It has long been recognized that NPC may have a variety of interwoven causes. There is strong evidence linking this cancer to three well defined factors: (a) a close association with the ubiquitous Epstein-Barr virus, (b) certain traditional Southern Chinese diets containing chemical carcinogens, coupled with insufficient intake of fresh fruits and vegetables and, (c) an inherited genetic predisposition to the disease in certain patients. The relative importance of these factors in causing NPC, and their mutual interaction, are not well understood. However, it is thought that these factors, in isolation or in combination, cause multiple gene alterations in tumour suppressor genes and the protooncogenes. These genetic alterations lead to a multi-step loss of normal gene functions, and disrupt the harmonious checks and balances which regulate cell growth and development. The accumulation of such genetic alterations in the nasopharyngeal mucosal cells will eventually lead to the development of nasopharyngeal cancer.

With the rapid advancement of molecular biology in the last few decades, investigation of such genetic events has become increasingly important in cancer research. Dr. Huang's research team has demonstrated that in NPC cancer cells, there is a consistent and nonrandom loss of segments on the short arms of chromosome 3 and chromosome 9 at specific locations (3p14 and 9p21). This has been demonstrated by cytogenetic analysis and by 'detailed deletion mapping' on the short arms of both chromosomes with 21 overlapping genetic markers (Microsatellite Polymorphisms Analysis) as illustrated in Figs. 1 and 2 below. Findings like these, and the consistency with which such genetic defects occur in patients suggest that NPC-associated suppressor genes reside on the short arms of both chromosomes at the identified regions. The defects and the loss of functions of these genes facilitate the development of the cancer.

Of particular interest is segment p21 of chromosome 9, which has been suggested to contain a gene named p16 (now known formally as the CDKN2 gene) that shows tumour suppressor function. Its protein product inhibits a complex machinery that tells cells to divide. Its loss of function might therefore lead to the uncontrolled division of cells.

The p16 gene and its association with some common cancers such as melanoma, lung cancer, gliomas (the most common type of brain tumours), esophageal, pancreatic and bladder cancers, have been the focus of interest in several major cancer research centres for the past few months. It has also become the hottest and the most controversial topic in the field of genetic cancer research. One immediate task for the CUHK team would be to investigate if the p16 gene on the short arm of chromosome 9 in nasopharyngeal carcinoma is at fault. Once the defective gene is confirmed and identified, it will be important to translate this scientific information to clinical situations as early warning markers for diagnosis of NPC and treatment such as gene-therapy.