Nasopharyngeal carcinoma (NPC), a relatively rare type of head and neck cancer, is also known as the "Cantonese" cancer in view of its high prevalence among the Southern Chinese and those of Cantonese origin. Around 80% of the illness occurs in southern China and among Chinese in the Southeast Asian region. Statistics also show that this group are about 30 times more susceptible to the disease than their western counterparts. This heavy ethnic and geographic distribution suggests both genetic susceptibilities as well as environmental factors in its development and research has confirmed this hypothesis, demonstrating genetic, environmental and viral factors as triggering its onset. NPC appears to be generated first of all from genetic factors creating a greater susceptibility to the illness. The situation is aggravated by chemical carcinogens – in salt fish and other preserved foods for example – in the regional diet. Subsequent infection by the Epstein-Barr (EBV) virus leads to the proliferation of "infected" cells, resulting in the development of NPC.

Radiotherapy is an effective treatment in the early stages of NPC – more than 80% of patients treated in this way have gone on to beat the illness. However treatment is much more difficult and less effective for patients diagnosed in the later stages of the illness. Seeking to better understand the disease and find more effective therapies for its treatment, a research study was recently completed by researchers at the Prince of Wales Hospital, the Chinese University of Hong Kong, the University of Hong Kong as well as the University of California San Francisco in the United States, to unveil the genetic properties of this cancer.

Discussing the study, Professor Lo Kwok Wai, the Principal Investigator of the study said, "Hong Kong has one of the highest incidences of NPC in the world with around 25 to 30 patients per 100,000 people. Systematically screening for genetic abnormalities involved in the development of NPC, our goal was to identify the "molecular markers" that would not only help in its early diagnosis, prognosis and monitoring, but also to enable the development of anti-cancer drugs and new methods of treatment."

Commencing in 2003, the study worked with a series of 21 NPC tissue samples from the Prince of Wales and Queen Mary Hospitals as well as three cell lines and 2 xenografts,

in conjunction with a process called array-based Comparative Genomic Hybridization Analysis (CGH), to generate two high-resolution NPC genome maps at 3Mb and 35 kb intervals. These maps revealed a number of common "amplicons" or "amplification" regions of affected cells indicating where oncogenes were likely to be located. Two chromosomes, at 11q13 and 12p13.3, were further characterized as the most common regions of gain, with upto 50-70% of primary NPC cells. Detailed analysis subsequently demonstrated that within the 5.3kb amplicon at 11q13, the CCND1 gene, and its encoding protein Cyclin D1, which is a key component for cell cycle regulation, was a target oncogene for NPC.

Amplification and over expression of Cyclin D1 was found in the majority of primary tumours, and functional studies have also shown its amplification as being critical to the development of NPC tumours. Targeting the inhibition of Cyclin D1 could therefore be an effective treatment for the disease. Some work has already been done in this direction – siRNA (small/short interfering Ribonucleic Acid) was introduced into two cell lines in the study, resulting in significant cell arrest and reduction of cell proliferation in the samples.

Looking forward, more work is being done in the effective use of these gene therapies to explore the anti-tumour effects of various pharmacological agents targeting Cyclin D1 and cell cycle regulation. At the same time work is also proceeding on the 12p13.3 amplification region where two possible NPC oncogenes, LTBR and FLJ10665, have been identified for further study. Additionally, apart from the amplifications identified, the high-resolution genome maps have also revealed a number of gene deletions and copy number variants. Ongoing studies of these areas will help to identify critical tumour suppressor genes and determine genetic areas that are susceptible to NPC, greatly helping to treat and control this common illness into the future.

Prof. LO Kwok Wai
Department of Anatomical & Cellular Pathology,
The Chinese University of Hong Kong
kwlo@cuhk.edu.hk