Mitochondrial NADH Dehydrogenase Subunit 3 ( MTND3 ) Polymorphisms are Associated with Gastric Cancer Susceptibility

• Published in: International journal of medical sciences Vol. 15; no. 12; pp. 1329 - 1333
• Main Authors: Jin, Eun-Heui, Sung, Jae Kyu, Lee, Sang-Il, Hong, Jang Hee
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher 01.01.2018
• Subjects: Case-Control Studies; Female; Genetic Predisposition to Disease; Genotype; Humans; Male; Middle Aged; NADH Dehydrogenase; Polymorphism, Single Nucleotide; Republic of Korea; Research Paper; Stomach Neoplasms - genetics; Republic of Korea; MTND3; Mitochondria; polymorphism; gastric cancer
• ISSN: 1449-1907; 1449-1907
• DOI: 10.7150/ijms.26881

Accumulating evidence indicates that mitochondrial DNA alterations contribute to cancer development and progression. In this study, we evaluated the relationship between polymorphisms of mitochondrial NADH dehydrogenase subunit 3 ( ) and the risk of gastric cancer (GC). Five single nucleotide polymorphisms (SNPs; rs28358278, rs2853826, rs201397417, rs41467651, and rs28358275) were identified and genotyped in 377 patients with GC patients and 363 controls by direct sequencing. The rs41467651 T allele was significantly associated with GC risk [adjusted odds ratio (OR) = 2.11, 95% confidence interval (CI) = 1.25-3.55, = 0.005). In stratified analysis, rs28358278, rs2853826, and rs41467651 were associated with subgroups of GC, with the rs28358278 G, rs2853826 T, and rs41467651 T alleles associated with an increased GC risk in females (adjusted OR = 1.70, 95% CI = 1.08-2.69, = 0.023; adjusted OR = 1.78, 95% CI = 1.11-2.85, = 0.016; adjusted OR = 2.07, 95% CI = 1.04-4.12, = 0.038, respectively). The rs441467651 T allele was also related with GC risk in diffuse-type subjects compared to that of controls (adjusted OR = 2.61, 95% CI = 1.43-4.89, = 0.002). In addition, The rs441467651 T allele was significantly related with increased GC risk regardless of lymph node metastasis (LNM), T classification, and tumor stage compared to that of controls (adjusted OR = 2.00, 95% CI = 1.12-3.55, = 0.019 in LNM-negative subjects; adjusted OR = 2.10, 95% CI = 1.05-4.22, = 0.0379 in LNM-positive subjects; adjusted OR = 1.82, 95% CI = 1.02-3.24, = 0.042 in T1/T2 subjects; adjusted OR = 2.60, 95% CI = 1.29-5.24, = 0.007 in T3/T4 subjects; adjusted OR = 1.91, 95% CI = 1.09-3.34, = 0.025 in tumor stage I (A+B)/II (A+B+C) subjects; adjusted OR = 2.36, 95% CI = 1.12-5.13, = 0.025 in tumor stage III (A+B+C) subjects) compared to that of controls. Our findings suggest that the rs28358278, rs2853826, and rs41467651 polymorphisms of increase the susceptibility to GC development.