Effects of carcinogenic metals on oral cancer in Changhua in Taiwan

1. Effects of carcinogenic metals on oral cancer in Changhua in Taiwan Introduction Oral cancer is one of the fastest increasing malignancies in Taiwan. An alarming 5.3-fold increase for men and a 2-fold increase for women in past two decades. Changhua has ranked as the top county in oral cancer incidence in Taiwan in recent years. Oral cancer incidence in Changhua has an exceptionally close relation with prevalence of BQC. Comparing to rest of Taiwan, the age of diagnosis, the common site and the trend of ASIR of oral cancer are different in Changhua. MMPs are a family of metal-dependent proteolytic enzymes that mediate the degradation of ECM and basement membranes. Type IV collagen is the main component of basement membrane and degradation of this structural protein is favored by two metalloproteases, MMP-2 and MMP-9. MMP-2 and MMP-9 are known to be closely associated with the malignant potentials of tumor cells. Various investigators have found that the polymorphism and expression of MMP-2 and MMP-9 are related to oral cancer. Materials and Methods We are collecting 100 cases from Division of Oral & Maxillofacial Surgery and 200 controls from Division of Allergy & Rheumatology in CCH, matching by gender and age (±2). All subjects will implement a questionnaire and be collected 9mL blood sample. Then, DNA is extracted and plasma and cells are separated. Both cancerous and non-cancerous oral tissues were taken from oral cancer patients. Trace elements conc. in tissue and blood will be measured by inductively coupled plasma mass spectrometry (ICP-MS). Tzu-Hsuen Yuan,1 Yaw-Huei Hwang,1 Che-Chun Su,2 Yang-Kuo Tsai,2 Ie-Bin Lian,3 Tsun-Kuo Chang,4 Chi-Ting Chiang4 1Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University, Taipei, Taiwan 2Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan 3Institute of Statistics and Information Science, National Changhua University of Education, Changhua, Taiwan 4Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, Taiwan With the unfrozen DNA, cells and plasma, MMP-2 and MMP-9 promoter gene polymorphism, MMP-2 and MMP-9 mRNA expression, and MMP-2 and MMP-9 protein amount will be measured by polymerase chain reaction (PCR). Figure 4. The route from the DNA code to the protein Electroplating is the major industry in Changhua and various kinds of heavy metals are utilized in this industry. Subjects in the areas with a high density of electroplating factories had significantly higher blood Cr and urinary Ni levels. Oral cancer patients living in the north/middle area of Changhua have younger age at diagnosis and have a poorer long-term prognosis. Results Figure 2. Trends in age-standardized incidence rate of male oral cancer with respect to age at diagnosis for each quadrennium. Besides, the most common site of oral cancer was the buccal mucosa in Changhua. In contrast, it was the tongue in the rest of Taiwan. The arithmetic distances between the two ASIR lines kept increasing. After separating Changhua in three areas according to theChanghua County Administration, there are some interesting things revealed. Figure 1. The 26 townships of Changhua County and the north areas with the high density of electroplating factories Figure 3. Age-standardized incidence rate of male oral cancer in Changhua versus that in the rest of Taiwan from 1986 to 2001. Table 4. Factory density in the north, middle, and south area of Changhua Figure 5. The distribution of the incidence rate of oral cancer in Taiwan Figure 2. Domain structure of MMP-2 and MMP-9 Cr, Ni, and As had found to stimulate MMP-2 and MMP-9 expression. And there were elevated metal conc. in lung and stomach cancerous tissue. Figure 4. Kaplan–Meier curves for 754 oral cancer patients at CCH from 1994 to 2001. In three areas, the north has the highest factory density. In particular, the densities of the electroplating factoryare strikingly different. In addition, the north and the middle areas have a significantly lower long-term survival (≧5 years) compared to the south. Figure 3. the hypothesis of effects of heavy metals on oral cancer Figure 6. The distribution of the nickel concentration in soil in Taiwan Discussion & Future Work Depending on the evidences, there are many distinctive features of oral cancer inChanghua and other factors, such as environmental pollution especially for metal, may be present locally and could be a factor. By the case-control study, we want to find out the risk factor in environment and occupation and the important biomarker of oral cancer in blood. In the future, we will compare the metal conc. in paired cancerous and non-cancerous human oral tissues and investigate the relationship among genetic polymorphism, related factors and oral cancer.