title: Oral epithelium as a surrogate tissue for assessing smoking-induced molecular alterations in the lungs.
abstract: The lungs and oral cavity of smokers are exposed to tobacco carcinogens. We hypothesized that tobacco-induced molecular alterations in the oral epithelium are similar to those in the lungs, and thus the oral epithelium may be used as a surrogate tissue for assessing alterations in the lungs. We used methylation-specific PCR to analyze promoter methylation of the p16 and FHIT genes at baseline and 3 months after intervention in 1,774 oral and bronchial brush specimens from 127 smokers enrolled in a randomized placebo-controlled chemoprevention trial. The association between methylation patterns in oral tissues and bronchial methylation indices (methylated sites / total sites per subject) was analyzed in a blinded fashion. At baseline, promoter methylation in bronchial tissue was present in 23% of samples for p16, 17% for FHIT, and 35% for p16 and FHIT; these percentages were comparable to methylation in oral tissue: 19% (p16), 15% (FHIT), and 31% (p16 and FHIT). Data from both oral and bronchial tissues were available for 125 individuals, in whom the two sites correlated strongly with respect to alterations (P < 0.0001 for both p16 and FHIT). At baseline, the mean bronchial methylation index was far higher in patients with oral tissue methylation (in either of the two genes; 39 patients) than in patients without oral tissue methylation (86 patients): 0.53 +/- 0.29 versus 0.27 + 0.26 methylation index (P < 0.0001). Similar correlations occurred at 3 months after intervention. Our results support the potential of oral epithelium as a surrogate tissue for assessing tobacco-induced molecular damage in the lungs and thus have important implications for designing future lung cancer prevention trials and for research into the risk and early detection of lung cancer.
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030-4009, USA.
authors.forename: Manisha
authors.initials: M
authors.lastname: Bhutani
authors.forename: Ashutosh Kumar
authors.initials: AK
authors.lastname: Pathak
authors.forename: You-Hong
authors.initials: YH
authors.lastname: Fan
authors.forename: Diane D
authors.initials: DD
authors.lastname: Liu
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.forename: Hongli
authors.initials: H
authors.lastname: Tang
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Kurie
authors.forename: Rodolfo C
authors.initials: RC
authors.lastname: Morice
authors.forename: Edward S
authors.initials: ES
authors.lastname: Kim
authors.forename: Waun Ki
authors.initials: WK
authors.lastname: Hong
authors.forename: Li
authors.initials: L
authors.lastname: Mao
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000235:genetics; D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D019942:Genes, p16; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D025202:Molecular Diagnostic Techniques; D009061:Mouth Mucosa / Q000378:metabolism / Q000473:pathology*; D009363:Neoplasm Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D012907:Smoking / Q000009:adverse effects*; D020340:Tobacco Use Cessation; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D015415:Biomarkers; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase