[Correlation of aberrant methylation of MGMT gene to MTHFR C677T genetic polymorphisms in esophageal squamous cell carcinoma].
OBJECTIVE
As one of the principal causes of gene inactivation, aberrant hypermethylation in the promoter of cancer-related genes has attracted more and more attention. However, such studies on esophageal cancer are still limited. This study was to investigate the association between aberrant hypermethylation of MGMT gene and clinical characteristics as well as MTHFR C677T genetic polymorphisms in esophageal squamous cell carcinoma in a Chinese population.


METHODS
A molecular epidemiologic study was conducted at Yangzhong County, Jiangsu Province of China, on histologically confirmed esophageal squamous cell carcinoma patients who were operated in the People's Hospital of Yangzhong County between January 2005 and March 2006. Peripheral blood samples, esophageal cancer tissues and paracancerous normal tissues were collected. Methylation-specific polymerase chain reaction(MSP) was used to detect the CpG island methylation status of MGMT gene. Restrictive fragment length polymorphism (RFLP) technique was used to test polymorphisms of folate metabolism enzyme gene MTHFR. The association between methylation status of MGMT gene and clinical characteristics as well as MTHFR C677T polymorphisms were analyzed.


RESULTS
Among 125 esophageal squamous cell carcinoma patients, the aberrant hypermethylation rate of MGMT gene was 27.2% in cancer tissues and 11.2% in paracancerous normal tissues. No hypermethylation was found in normal esophageal tissues from 10 healthy adult subjects. Methylation rate of MGMT gene in cancer tissues was significantly higher in the patients with lymph node metastasis than in those without lymph node metastasis (37.3% vs. 18.2%, P=0.017). No association was found between aberrant DNA methylation and selected factors including sex, age, tobacco smoking, alcohol drinking and green tea drinking. After adjusting by potential confounders, variant allele of MTHFR C677T was found to be associated with hypermethylation of MGMT gene. Compared with wild type CC, the odds ratio was 3.34 (95% CI: 1.07-10.39) for CT and 3.83 (95% CI: 1.13-12.94) for TT.


CONCLUSIONS
Aberrant CpG island hypermethylation of MGMT gene is closely related with the genesis and progression of esophageal squamous cell carcinoma.
Xue
Heng-Chuan
HC
Department of Thoracic Surgery,People's Hospital of Yangzhong, Yangzhong, Jiangsu, 212200, P. R. China. yzxhcys@163.com
Wang
Jian-Ming
JM
Xu
Biao
B
Guo
Guo-Ping
GP
Hua
Zhao-Lai
ZL
Zhou
Qin
Q
Zhu
Zong-Hai
ZH
Ma
Zhen-Kai
ZK
Gao
Jie
J
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D011795:Surveys and Questionnaires; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D025521:Tumor Suppressor Proteins; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes