title: Correlation ofMLH1andMGMTmethylation levels between peripheral blood leukocytes and colorectal tissue DNA samples in colorectal cancer patients.
abstract: CpG island methylation in the promoter regions of the DNA mismatch repair gene mutator L homologue 1 (MLH1) and DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT) genes has been shown to occur in the leukocytes of peripheral blood and colorectal tissue. However, it is unclear whether the methylation levels in the blood leukocytes and colorectal tissue are correlated. The present study analyzed and compared the levels ofMGMTandMLH1gene methylation in the leukocytes of peripheral blood and colorectal tissues obtained from patients with colorectal cancer (CRC). The methylation levels ofMGMTandMLH1were examined using methylation-sensitive high-resolution melting (MS-HRM) analysis. A total of 44 patients with CRC were selected based on theMLH1andMGMTgene methylation levels in the leukocytes of the peripheral blood. Corresponding colorectal tumor and normal tissues were obtained from each patient and the DNA methylation levels were determined. The correlation coefficients were evaluated using Spearman's rank test. Agreement was determined by generalized κ-statistics. Spearman's rank correlation coefficients (r) for the methylation levels of theMGMTandMLH1genes in the leukocytes of the peripheral blood and normal colorectal tissue were 0.475 and 0.362, respectively (P=0.001 and 0.016, respectively). The agreement of theMGMTandMLH1gene methylation levels in the leukocytes of the peripheral blood and normal colorectal tissue were graded as fair and poor (κ=0.299 and 0.126, respectively). The methylation levels ofMGMTandMLH1were moderately and weakly correlated between the patient-matched leukocytes and the normal colorectal tissue, respectively. Blood-derived DNA methylation measurements may not always represent the levels of normal colorectal tissue methylation.
authors.affiliation: Department of Epidemiology, Public Health College, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Yibaina
authors.initials: Y
authors.lastname: Wang
authors.forename: Zuoming
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Yao
authors.forename: Jie
authors.initials: J
authors.lastname: Ge
authors.forename: Yashuang
authors.initials: Y
authors.lastname: Zhao
keywords: MGMT; MLH1; colorectal cancers; methylation