Single nucleotide polymorphisms in the mitochondrial displacement loop and outcome of esophageal squamous cell carcinoma

Abstract

BackgroudAccumulation 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.MethodsThe 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.ResultsThe 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).ConclusionGenetic 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.

Mitochondrial DNA haplogroup M is associated with late onset of hepatocellular carcinoma

“…We have previously performed a number of studies on D-loop SNPs as predictive factors for digestive tract cancers (24,25,29). In the present study, for the first time, we suggest that, other than as predictors for cancer risk and outcome, SNPs in the D-loop are also predictors for age-at-onset in HCC patients.…”

Identification of sequence polymorphisms in the displacement loop region of mitochondrial DNA as a risk factor for renal cell carcinoma

“…In our study, all the cancer risk-associated SNPs were identified in the HV segment region of the D-loop, with nucleotides 16293, 16298 and 16319 belonging to HV-Ⅰ, 262 to HV-Ⅱ and 488 to HV-Ⅲ. Cancer risk-and outcome-associated SNPs were identified in these regions in other types of cancer as well, including esophageal squamous cell carcinoma (17,27) and hepatocellular carcinoma (25,26). The HV segments are mutational hotspots at which germline and tumor mtDNA mutations preferentially occur (28).…”

“…An increase of mutations and SNPs in the mitochondrial D-loop region have been reported in a variety of cancers, including esophageal squamous cell carcinoma (17), hepatocellular carcinoma (18), oral squamous cell carcinoma (19) and lung cancer (20). In this case-control study, cancer risk-associated SNPs for RCC were investigated in a continuous sequence of mtDNA between nucleotides 16190 and 583, and 5 SNP sites, comprising 16293, 262, 488, 16298 and 16319, were identified.…”

Sequence polymorphisms of the mitochondrial displacement loop and outcome of non-small cell lung cancer

“…We previously identified cancer risk and outcome-associated SNPs of the D-loop in several types of cancer (25,26,30). In this study, selected SNPs in the mtDNA D-loop were examined for their ability to predict cancer outcome in NSCLC patients.…”