Effects of carcinogenic metals on oral cancer in Changhua in Taiwan

1. Effects of carcinogenic metals on oral cancer in Changhua in Taiwan Background & Objective Oral cancer is one of the fastest increasing malignancies in Taiwan. 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. 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. Based on the serious metal contamination in soil and the distinctive prevalence of oral cancer in Changhua, the aims of this study is to clarify the relationship of metals and oral cancer in this peculiar area by conducting a case-control study. Tzu-Hsuen Yuan,1 Yaw-Huei Hwang,1 Che-Chun Su,2 Kuo-Yang 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 Table 2. Metals in blood of cases and controls from CCH, TaiwanUnit =μg/L Cases (n = 106) Controls (n = 70) Mean (SD) Mean (SD) Cr 0.84 (0.32)* 0.63 (0.23) Ni 1.61 (0.57)* 0.93 (0.42) Cd 0.98 (0.62) 0.97 (0.60) As 5.14 (5.83) 5.42 (3.44) Hg 8.30 (11.0) 8.59 (6.69) Pb 33.1 (20.8) 28.9 (16.0) Cu 879 (178) 822 (228) Zn 6690 (1089)* 6165 (901) n = sample size; Mean = arithmetic mean; SD = standard deviation; * = p < 0.05 Table 3. Odds ratios (ORs) for oral cancer according to the potential risk factors Factors Cases Controls OR (95% CI) P Value Alcohol drinking Non-drinker 36 43 1.00 Drinker 65 27 2.88 (1.53-5.40) <0.001 Smoking Non-smoker 10 32 1.00 Smoker 91 38 7.66 (3.43-17.13) <0.0001 Betel quid chewing Non-chewer 12 46 1.00 Chewer 89 24 14.22 (6.52-30.98) <0.0001 Nearby environment lower polluted 46 48 1.00 higher polluted 54 22 2.56 (1.35-4.86) <0.01 Materials & Methods We are collecting around 100 cases from Division of Oral & Maxillofacial Surgery and 100 controls from Division of Allergy & Rheumatology in Changhua Christian Hospital (CCH), matching by gender and age (±3). All subjects will implement a questionnaire to collect the information on demographics, lifestyle, smoke, alcohol, and betel quid consumption, environmental and occupational exposure history, and family history of cancer and be collected blood sample. Trace elements conc. in blood will be measured by inductively coupled plasma mass spectrometry (ICP-MS). For the precision and accuracy of the ICP-MS determination for metal levels in blood samples, spike solutions will be detected to make sure the stability during the analysis process. The certified reference whole blood Seronorm L1 & L3, which contain low and high concentrations, respectively, of trace metals in human blood, will be analyzed for accuracy assessment. μg/L μg/L μg/L Figure 1. The comparison of different conditions of risk habits on metal conc. in blood in cases Results Table 4. Result of logistic regression model of oral cancer on the potential risk factors p Value β OR* 95% lower 95% upper Betel quid <0.0001 1.465 18.74 5.939 59.11 Cr <0.001 4.294 73.26 7.306 734.6 Ni<0.0001 3.805 44.91 9.637 209.3 Table 1. Characteristics of cases and controls from CCH, Taiwan Variables Case (n = 101) Control (n = 70) Number (%) Number (%) Age (years) <40 1 (0.9) 1 (1.4) 40-49 27 (26.7) 13 (18.6) 50-59 37 (36.6) 22 (31.4) 60-69 28 (27.7) 21 (30.0) <70 8 (7.9) 13 (18.6) Sex Male 96 (95.0) 59 (84.3) Female 5 (5.0) 11 (15.7) Residence North Changhua 24 (23.8) 32 (45.7) Middle Changhua 35 (34.7) 19 (27.1) South Changhua 23 (22.8) 5 (7.1) Other County 19 (18.8) 14 (20.0) *Estimated odds ration from logistic coefficients Discussion & Conclusion In this study, the blood conc. of Cr, Ni, and Zn in cases were significantly higher than those in controls. In addition to known risk factors, the environment of the neighborhood of residence and the Cr and Ni conc. in blood were found to be related to oral cancer. After adjusted the potential confounders, it showed high correlation between oral cancer and betel quid, Cr, and Ni. There was no epidemiological study to observe that oral cancer correlates with Cr and Ni. Epidemiological studies have implicated Ni compounds as human carcinogens and recent research has shown that soluble Cr(VI) administered chronically in drinking water can induce oral and intestinal tumors. Furthermore, the role of Cr and Ni on the mechanism of oral cancer has been suggested and required further detailed and comprehensive investigation. Neighborhood environment Higher polluted 54 (54.0) 22 (31.4) Lower polluted 46 (46.0) 48 (68.6) n = sample size