MGMT Hypermethylation And Interaction With Environmental Factors In Esophageal Cancer

BackgroundEsophageal cancer ranked as the eighth most frequent and sixth most fatal cancer in the world.This malignancy exists in two forms;esophageal squamous cell carcinoma and esophageal adenocarcinoma.China alone contributed almost half of the 455,800 global new esophageal cancer cases in 2012,and the incidence of esophageal cancer was ranked fifth,and mortality rate ranked fourth of all cancer in Chinese population.Genetic and environmental factors are known to contribute to the development of complex diseases.Epigenetic modifications,like MGMT hypermethylation,have been increasingly noticed to induce transcriptional silencing in both subtypes of esophageal cancer.Here,we aimed at assessing the association between MGMT hypermethylation and the risk for EC in patients from Huai’an district.MethodsHospital-based case-control study data was utilized for 110 ECP diagnosed by pathology or endoscopy from Huai’an district.Before recruitment,written consent was obtained from each subject.A structural questionnaire was administered to collect demographic information such as age,gender and educational level,personal life habits,dietary conditions and disease health status.At the same time,a 5ml sample of blood was obtained from each subject in heparinized tubes.We collect fresh surgical tissue from patients,including two cancer tissues and two adjacent tissues of the distal tumor.Using cases only,we performed conditional logistic regression to determine the association between MGMT hypermethylation and the risk for esophageal ResultsA Total of 110 cases of esophageal cancer patients were included in this analysis.55.5% of the participants were female and 44.5% male,the mean(SD)age being 58.9(7.6)years.31.2%of the participants came from urban Huai’an District,23.9% from Sub-urban-Huai’an District and a more significant proportion were from the rural area district of Huai’an 45.0%.Of the 110 EC cases,genotype data were available for 105 participants.80.0% of the healthy tissues extracted from the tumor tissue of ECP were unmethylated and 20.0% methylated.Similarly,50.5% of cancer tissues extracted from normal tissue adjacent to the tumor of ECP were unmethylated and 49.5% methylated.Result to determine the association MGMT hypermethylation,and the risk of esophageal cancer showed a significant association between MGMT hypermethylation and the risk of esophageal cancer(COR= 8.75;95% CI: 3.11-4.619).A significant association was observed between blood and CT mgmt-methyl,the Chi-square being 8.508 and p-value= 0.004.The result from gene-environment analyses revealed that a positive synergistic interaction existed between MGMT methylation and Cigarette smoking(COR = 1.66,95% CI: 0.63-4.34),between MGMT methylation and spicy food(COR =1.43,95% CI: 0.51-3.61)and between MGMT methylation and history of digestive tract diseases(COR = 1.56,95% CI: 0.51-4.80).In contrast,no other synergistic interactions were observed.ConclusionsOur investigation indicates that MGMT hypermethylation has potential to increase the risk of EC.Also,our investigation revealed that blood MGMT methyl is strongly related to Ct MGMT methyl in ECP,which can be used as a biomarker for early detection of EC.