Associations between Single Nucleotide Polymorphisms in the Mitochondrial DNA D-Loop Region and Outcome of Gastroenteropancreatic Neuroendocrine Neoplasm

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Abstract.Accumulation of single-nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) may be associated with cancer risk and disease outcome. We evaluated the predictive value of these SNPs for GEP-NEN outcome. Three SNP sites of nucleotides16257C/A, 150C/T and 151C/Tdel were identified for statistically significant prediction of postoperative survival in GEPNEN by univariate analysis with log-rank test. In addition, the minor haplotype of nucleotides 16257A in the hypervariable segment 1(HV1) region of the D-loop was identified for their association with lower survival rate of GEP-NEN (relative risk, 3.390; 95% CI, 1.071˜10.729; p=0.038) by multivariate analysis with COX hazards model. The analysis of genetic polymorphisms in the mitochondrial D-loop can help identify patient subgroups with a high risk of GEP-NEN outcome.

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