Association between the methylations of RUNX3 in peripheral blood and lung cancer: a case-control study.

Background: RUNX3 is hypermethylated in multiple cancers. TIMP2 also functions as a regulator of tumors. However, there are only very few reports on the association of methylation of RUNX3 and TIMP2 with lung cancer (LC) in peripheral blood. Methods: 426 LC patients and 428 age- and sex-matched healthy controls were recruited. DNA methylation in blood was semi-quantitively assessed by mass spectrometry. For the association analysis, binary logistic regression analysis adjusted covariant was applied, and ORs were presented as per +10% methylation. Results: Hypermethylation of CpG_1, CpG_5and CpG_8 in RUNX3 was significantly associated with LC (ORs = 1.45, 1.35 and 1.35, respectively, adjusted p  < 0.05), and even Stage I LC. The association between the three RUNX3 CpG sites and LC was enhanced by increased age (> 55 years, ORs ranged from 1.43 to 1.75, adjusted p  < 0.05), male gender (ORs ranged from 1.47 to 1.59, adjusted p  < 0.05) and tumor stage (Stage II&III&IV, ORs ranged from 1.86 to 3.03, adjusted p  < 0.05). Conclusions: This study suggests a significant association between blood-based RUNX3 hypermethylation and LC, especially in elder people, in males and in LC patients with advanced stage.