Sequence variations of mitochondrial DNA D-loop region are associated with familial nasopharyngeal carcinoma

Mitochondrial DNA (mtDNA) D-loop has been identified as a frequent hot spot of mutations in various tumors. The aim here was to investigate the sequence variations of mitochondrial D-loop region in familial nasopharyngeal carcinoma (FNPC) and their possible associations with cancer risk. 29 subjects from 4 Chinese NPC families and 20 sporadic NPC as well as 122 cases of normal control were recruited. mtDNA extracted from peripheral blood was examined by PCR-based assay for D-loop sequence variations, followed by sequencing analysis. Compared with normal control, four high variations and 6 unrepoted novel polymorphisms were found. Particularly, the np16362 and 16519T to C variants show significantly higher (100%, 81.8%) and lower (0, 22.7%) frequencies in FNPC and unaffected pedigree members, respectively. The occurrence of mitochondrial microsatellite instability (mtMSI) at D310 in experimental groups was statistically significantly higher than in normal control (53.3%). Likewise, in Base Variation Rate consistent with the result, there was a statistically significant difference compared with NC (6.05%). Our results indicated that mtDNA exhibited a high rate of sequence variants in patients with NPC and pedigree members and the mtDNA np16362, np16519 variants and mtMSI at D310 are associated with an increased risk of familial nasopharyngeal carcinoma in pedigree members from families with NPC, which might be involved in the NPC carcinogenesis.