title: [Gene methylation in stool for the screening of colorectal cancer and pre-malignant lesions].
abstract: OBJECTIVE
  To evaluate association between DNA methylation of MAL, CDKN2A, and MGMT in stool and development of colorectal cancer, and to evaluate the screening value of these biomarkers in colorectal cancer and pre-malignant lesions.
  
  
  METHODS
  Morning stool specimens were collected from 69 patients with colorectal cancer, 24 with colon adenoma, 19 with hyperplastic polyps, and 26 healthy controls. DNA was extracted and treated with bisulfite. Methylation-specific PCR(MSP) was performed for methylation analysis of MAL, CDKN2A and MGMT in DNA samples. Associations between clinicopathological features and gene methylation were analyzed. The sensitivity of diagnosis by combining three methylation markers was compared with fecal occult blood test(FOBT).
  
  
  RESULTS
  The methylation frequencies of MAL, CDKN2A and MGMT were 78.3%, 52.5% and 55.1% in colorectal cancer, 58.3%, 41.7% and 37.5% in colon adenomas, 26.3%, 15.8% and 10.5% in hyperplastic polyps, and 3.8%, 0 and 3.8% in healthy controls, respectively. Significant differences in three genes were found between colorectal cancer and hyperplastic polyp, colorectal cancer and healthy control, colon adenoma and hyperplastic polyp, colon adenoma and healthy control(all P<0.05). The diagnostic sensitivity by combining three methylation markers was 92.8% in colorectal cancer, 70.8% in colon adenomas, significantly higher than FOBT examination (29.0% in colorectal cancer and 25.0% in colon adenomas, all P<0.05). No significant associations existed between three genes methylation of the three genes and clinical characteristic including sex, age, tumor location, lymph node metastases and TNM stage (all P>0.05).
  
  
  CONCLUSIONS
  DNA methylations levels of MAL, CDKN2A, and MGMT in stools are significantly higher in colorectal cancer and colon adenoma, which may serve as an noninvasive approach for the screening of colorectal cancer and pre-malignant lesions.
authors.affiliation: Department of Colorectal Surgery, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China. fugang416@126.com.
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Kang
authors.forename: Fu-Ao
authors.initials: FA
authors.lastname: Cao
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Chang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Lou
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Wu
authors.forename: Chuan-Gang
authors.initials: CG
authors.lastname: Fu
authors.forename: Guang-Wen
authors.initials: GW
authors.lastname: Cao
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D019175:DNA Methylation; D055088:Early Detection of Cancer; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D019853:O(6)-Methylguanine-DNA Methyltransferase