Effect of different oral habits and lymphocytes subpopulation on oral cancer progression
Date Issued
2015
Date
2015
Author(s)
Yeh, Chien-Yang
Abstract
English Abstract In recent years, the prognosis for oral cancer patients is unpredictable even after different treatment modalities. We try to analyze whether betel quid (BQ) chewing, alcohol consumption and smoking habits may increase the risk of oral precancer and oral cancer. In addition, lymphocyte populations in patients may potentially affect the malignant transformation of oral pre-cancer in modern studies. We attempted to study whether oral habits or changes in lymphocyte subsets can be a biomarker for malignant transformation or cancer death in a cohort of patients with oral precancer and cancer. Moreover, a number of studies have found that chemical carcinogens may induce DNA damage, genotoxicity, cell proliferation and tissue inflammation and contribute to carcinogenesis. In the first part of study, we use C3H10T1/2 cell transformation assay to study the potential carcinogenicity of areca nut (AN). We showed that ANE and arecoline are cytotoxic to cells and may possibly affect the oral wound healing response. ANE exhibited tumor initiation effect and may induce transformation of C3H10T1/2 cells by the promotion of TPA. These effects may contribute to the pathogenesis of oral submucous fibrosis and oral cancer. Various carcinogens may play important roles in specific steps of chemical carcinogenesis by inducing DNA damage, cytotoxicity, cell proliferation, tissue inflammation, impairment of cell-cell communication. In the 2nd Part，we enrolled 28 patients with oral pre-cancer and 86 oral cancer patients were enrolled in this study and their personal information and oral habits were documented. Their lymphocyte populations (CD4+, CD8+, CD19+, CD56+ and their activation marker CD25 and CD69) were determined by flow cytometry on 2002-2004. After follow-up to Dec. 2014, patients with/without malignant transformation were recorded and evaluated their relation to oral habits and percentage of initial lymphocyte markers. Ten pre-cancer patients developed OSCC with a mean period of malignant transformation of 6.80 ± 2.13 years. Patients with malignant transformation showed mean age of 48.40 ± 4.97 (n=10), relatively higher than patients without malignant transformation (41.56 ± 6.27, n=18) (P<0.05). An increase in population of peripheral blood mononuclear cells expressing CD4+CD69+, CD19+CD69+, and CD56+CD69+ (p<0.05) in pre-cancer patients with malignant transformation was noted. Alcohol consumption showed an association with the malignant transformation of patients with pre-cancer (P=0.03), whereas BQ and smoking showed little effect. Conversely, we can find the ratio of malignant transformation without poor oral habits will be lower than patient with poor habits. It indicates the potential influence on oral carcinogenesis. In the 3rd part, 86 cases of oral cancer patients, researched over 10 years, we also found that the age (p<0.1) is related between the oral cancer groups, and drinking habits statistically associated with the death group (p<0.05). There is no obvious relationship between the BQ chewing and smoking habits with oral cancer death. It does not mean that BQ and smoking habit have no influence on cancer death, because most cancer patients have both of these oral habits. Lymphocyte subpopulations CD19+ (p<0.01), have significant relationship in the survival and death groups, CD56+ (p=0.05), CD56+CD69+ (p=0.06) have the upregulation tendency in the death group. A decrease of CD19+ suggests that B cell declined significantly in the late cancer patients’ body. These results are displayed human immune system may change during tumor development. Finally, the end of the 50 cancer patients died, the mortality rate more than 52% within three years. We concluded that areca nut components can be a tumor initiator, leading to the generation of initiated cells. Age and alcohol consumption, and the early activation of T cell, B cell and NK cells are crucial in the transformation of oral precancer to oral cancer. Moreover, age, alcohol consumption, and changes in B cells and NK cells in oral cancer patients are important for prediction of their future survival. Therefore, analysis of lymphocyte populations can be a diagnosis and an extra-prediction biomarker for malignant pathogenesis of oral cancer.
Subjects
Chemical carcinogenesis
oral cancer
oral precancer
lymphocyte population
oral habits
malignant transformation
SDGs
Type
thesis
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