Abstract 4654: Mitochondrial variants and clinical outcome of oral squamous cell carcinoma in Taiwan

Abstract

Abstract Mitochondria are essential cytoplasmic organelles, generating cellular energy in the form of adenosine triphosphate by oxidative phosphorylation. A large volume of studies have indicated that polymorphisms in the mitochondrial genome are associated with risk of various diseases, including cancer. However, only few studies examined the effect of polymorphisms on cancer outcome. To explore the possible role of mitochondrial polymorphisms on clinical outcome of oral squamous cell carcinomas (OSCCs) in Taiwan, 7 common length polymorphism (mtLP) sites and the control D-loop region of mitochondrial genome were genotyped or screened by DNA direct sequencing in 298 OSCCs. One hundred and seventy-eight single-nucleotide polymorphisms (SNPs) were found in the D-loop region and 19 SNPs were presented with a high frequency (> 10%) of variant form. The frequency of variant form in the mtLP sites were quite various ranging from 3.7% to 62.8%. In total, 7 variants from 6 polymorphism sites (2 mtLPs and 4 SNPs) were associated with overall survival. Four subgroups (clusters 1 - 4) were identified by hierarchical clustering of the OSCCs based on the genotypes of these 6 polymorphism sites. We found that the overall survival was significantly different among these 4 OSCC clusters. An index score designated as the total effects of the genotypes of these 6 polymorphism sites on survival for each individual was also developed using the estimates from the Cox model. We found that individual with the higher the index score had the poorer disease-free and overall survival. In summary, the findings provide the first evidence pointing toward mitochondrial variants affect the clinical outcome in OSCC and the underlying mechanisms are worthy to investigate. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4654.