Zhang et al. Journal of Experimental & Clinical Cancer Research 2010, 29:155 http://www.jeccr.com/content/29/1/155 R E S E A R C H Open Access Single nucleotide polymorphisms in the mitochondrial displacement loop and outcome of esophageal squamous cell carcinoma Ruixing Zhang1†, Rui Wang2†, Fengbin Zhang1, Chensi Wu1, Haiyan Fan1, Yan Li3, Cuiju Wang4, Zhanjun Guo1,5* Abstract Backgroud: Accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) has been described for different types of cancers and might be associated with cancer risk and disease outcome. We used a population-based series of esophageal squamous cell carcinoma (ESCC) patients for investigating the prediction power of SNPs in mitochondrial D-loop. Methods: The D-loop region of mtDNA was sequenced for 60 ESCC patients recorded in the Fourth Hospital of Hebei Medical University between 2003 and 2004. The 5 year survival curve were calculated with the Kaplan-Meier method and compared by the log-rank test at each SNP site, a multivariate survival analysis was also performed with the Cox proportional hazards method. Results: The SNP sites of nucleotides 16274G/A, 16278C/T and 16399A/G were identified for prediction of post- operational survival by the log-rank test. In an overall multivariate analysis, the 16278 and 16399 alleles were identified as independent predictors of ESCC outcome. The length of survival of patients with the minor allele 16278T genotype was significantly shorter than that of patients with 16278C at the 16278 site (relative risk, 3.001; 95% CI, 1.029 - 8.756; p = 0.044). The length of survival of patients with the minor allele 16399G genotype was significantly shorter than that of patients with the more frequent allele 16399A at the 16399 site in ESCC patients (relative risk, 3.483; 95% CI, 1.068 - 11.359; p = 0.039). Conclusion: Genetic polymorphisms in the D-loop are independent prognostic markers for patients with ESCC. Accordingly, the analysis of genetic polymorphisms in the mitochondrial D-loop can help identify patient subgroups at high risk of a poor disease outcome. Background Esophageal cancer is one of the commonest cancers in the population of northern central China with an age-standar- dized annual incidence rate > 125/100,000 [1]. Cumulative mortality attributed to esophageal cancer is approximately 20% for women and 25% for men [2]. The prognosis of esophageal cancer remains poor, despite improved diagno- sis and therapeutic strategies, mostly because of its aggres- sive nature. The performance status, the TNM stage, and lymph node metastases seem to be the predictive factors of esophageal cancer; some molecular factors, such as p53 * Correspondence: zjguo5886@yahoo.com.cn † Contributed equally 1Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University. Shijiazhuang, PR China Full list of author information is available at the end of the article mutaion and NF-kappaB expression level, also show pre- dictive power for esophageal cancer outcome [3]. The human mitochondrial genome is 16 kb in length and is a closed-circular duplex molecule that contains 37 genes, including 2 ribosomal RNAs and a complete set of 22 tRNAs [4]. mtDNA is believed to be more sus- ceptible to DNA damage and acquires mutations at a higher rate than nuclear DNA, because of the high levels of reactive oxygen species (ROS), the lack of protective histones, and limited capacity for DNA repair in the mitochondria [5,6]. In cancers patients, sequence changes accumulated extensively in the mitochondrial D-loop region, which is important for regulating both replication and expression of the mitochondrial genome, because it contains the leading-strand origin of replication and the main © 2010 Zhang et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.