title: Quantitative assessment of lung cancer associated with genes methylation in the peripheral blood.
abstract: BACKGROUND
  Lung cancer is the leading cause of cancer-related deaths worldwide due mainly to late diagnosis and poor prognosis. Aberrant promoter methylation is an important mechanism for silencing of tumor suppressor genes during carcinogenesis and a promising tool for the development of molecular biomarkers.
  
  
  METHODS
  We evaluated the p16, RASSF1A, and FHIT genes promoter methylation status in peripheral blood DNA between 200 lung cancer patients and 200 normal controls by using SYBR green-based quantitative methylation-specific PCR (qMSP).
  
  
  RESULTS
  There were statistically significant differences in the methylation status of p16, RASSF1A, and FHIT between the cancer cases and controls (p16: P = .008, RASSF1A: P = .038, FHIT: P = .002). When the subjects were categorized into quartiles based on the genes methylation status, the risk of lung cancer was found to increase as methylation status increased (p16: Ptrend = .002, RASSF1A: Ptrend = .014, FHIT: Ptrend = .001). When the median of methylation status was used as the cutoff between high and low methylation status, individuals with high methylation status were at a significantly higher risk of lung cancer than those with low methylation status (p16: adjusted odds ratio = 1.597, P = .028; RASSF1A: adjusted odds ratio = 1.551, P = .039; FHIT: adjusted odds ratio = 1.763, P = .008). In addition, there were no significant correlations between p16, RASSF1A, or FHIT methylation status and gender (P > .05), age (P > .05), smoking history (P > .05), histological type (P > .05), or clinical stage (P > .05).
  
  
  CONCLUSIONS
  These results suggest that the high methylation statuses of p16, RASSF1A, or FHIT genes were associated with a significantly increased risk of lung cancer; the risk of lung cancer increased as the methylation status increased. Further investigation of their definitive usefulness in clinical practice is warranted.
authors.affiliation: College of Public Health, Zhengzhou University, Zhengzhou, China.
authors.forename: Shanjuan
authors.initials: S
authors.lastname: Tan
authors.forename: Changqing
authors.initials: C
authors.lastname: Sun
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Wei
authors.forename: Yanqiang
authors.initials: Y
authors.lastname: Li
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yan
authors.forename: Feifei
authors.initials: F
authors.lastname: Feng
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Yiming
authors.initials: Y
authors.lastname: Wu
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000235:genetics; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D016017:Odds Ratio; D010641:Phenotype; D011401:Promoter Regions, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D000099170:Bis(5'-adenosyl)triphosphatase; C411762:RASSF1 protein, human