Abstract: Objective To explore the association of KCNMA1 gene methylation levels in peripheral blood with lung cancer. Methods The methylation levels of 4 CpG sites in KCNMA1 gene were quantitatively detected in 285 patients with lung cancer, 186 age- and sex-matched patients with benign pulmonary nodules and 278 matched healthy control subjects using mass spectrometry (MALDI-TOF-MS). The association of KCNMA1 methylation levels with lung cancer was analyzed using logistic regression models adjusted for covariates. The KCNMA1 methylation levels in different subgroups of lung cancer patients were compared using Mann-Whitney U test. Results In subjects over 55 years and in female subjects, the highest quartile (Q4) vs the lowest quartile (Q1) of KCNMA1_CpG_5 methylation levels were significantly correlated with lung cancer (for subjects over 55 years: OR=2.60, 95% CI: 1.25?5.41, P=0.011; for female subjects: OR=2.09, 95% CI: 1.03?4.26, P=0.042). From Q2 to Q4 of KCNMA1_CpG_5 methylation levels, their correlation with lung cancer became gradually stronger (P=0.003 and 0.038, respectively). In male subjects, the OR of Q4 of KCNMA1_CpG_5 methylation levels was 0.35 in patients with lung cancer as compared with patients with benign nodules (95% CI: 0.16 ? 0.79, P=0.012). KCNMA1_CpG_3 methylation level was significantly lower in invasive adenocarcinoma than in noninvasive adenocarcinoma (P=0.028), and that of KCNMA1_CpG_1 was significantly higher in patients with larger tumors (T2-4) than in those with smaller tumors (T1) (P=0.021). Conclusion The change of peripheral blood KCNMA1 methylation level is correlated with the occurrence and development of lung cancer.

Key words: lung cancer; KCNMA1; DNA methylation; peripheral blood; case-control study