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

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) are relatively rare tumors that arise from the diffuse neuroendocrine system, and the biggest advances in molecular biology have helped in understanding these biological diversity of tumors over the past decades. It is important to determine the carcinogenesis of GEP-NEN from the perspective of genetic backgrounds.

Mitochondrial DNA (mtDNA) of peripheral blood from 66 GEP-NEN patients and from 75 healthy controls without history of any cancer were examined for single nucleotide polymorphisms (SNPs) and mutations in the displacement loop (D-loop) region.

Single nucleotide polymorphisms were detected in 148 sites within the 982 bp mitochondria D-loop region from blood samples of healthy controls and GEP-NEN patients. SNPs with a rare allele frequency >5% in either controls or GEP-NEN patients were used for cancer risk analysis; a total of 23 SNPs were selected. When individual SNPs of GEP-NEN patients compared with healthy controls were analyzed, a statistically significant increase in the SNP frequency was observed for 73G, 150T, 151T, 492C, 16257A, 16261T, and 16399G in GEP-NEN patients (P<.05). It was also observed that the SNP frequency for 489C and 16519C significantly decreased in GEP-NEN patients compared with controls (P<.05).

In summary, SNPs in the mutations of the mitochondrial D-loop may be valuable markers for GEP-NEN risk evaluation. Analysis of the genetic polymorphisms in the D-loop may be useful for diagnosis of high-risk individuals.