Mitochondrial DNA alterations in male oral squamous cell carcinoma in Taiwan
| Autor: | Chih Hsiung Lai, 賴志雄 |
|---|---|
| Rok vydání: | 2013 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 101 Reprogramming of energy metabolism is one of the hallmarks of cancer cells and has been directly/indirectly linked to functional defects of mitochondria. Somatic mutations of mitochondrial DNA (mtDNA) have been frequently observed in human cancers and studies have indicated that mtDNA polymorphisms are associated with risk of various diseases including cancer. However, the clinical significance of these mtDNA alterations in cancer remains unclear. This study was therefore performed to explore the possible clinical relevance of mtDNA mutations and polymorphisms/haplotypes in 300 male oral squamous cell carcinoma (OSCC) patients. The whole mitochondrial genome was analyzed by direct sequencing. The main findings are: 1) Individuals who were members of the CZD haplogroup showed a significant association with better disease-free survival (DFS) than the other haplogroups after adjusting for tumor stage, differentiation and age at diagnosis (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.36 - 0.84). 2) About one quarter (74/300) of the OSCC tumors contained pathogenic mutations. 3) Individuals with the TP53 R allele had a higher frequency of pathogenic mutations than those with the PP genotype. 4) TP53 R allele patients with pathogenic mutations demonstrated a significant association with a poorer DFS than other individuals after adjusting for mtDNA haplogroup, tumor stage with treatment regimens, differentiation and age at diagnosis (HR = 1.54; 95% CI, 1.03 - 2.32). The results strongly indicate that an individual's haplogroup plays an important role in tumor behavior and pathogenic mtDNA mutations are a potential prognostic marker for OSCCs. Furthermore, dysfunctional mitochondria due to mtDNA pathogenic mutation may play an active role in cancer development and response to radiotherapy/chemo-radiotherapy. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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