PT  - JOURNAL ARTICLE
AU  - Bhutani, Manisha
AU  - Pathak, Ashutosh Kumar
AU  - Fan, You-Hong
AU  - Liu, Diane D.
AU  - Lee, J. Jack
AU  - Tang, Hongli
AU  - Kurie, Jonathan M.
AU  - Morice, Rodolfo C.
AU  - Kim, Edward S.
AU  - Hong, Waun Ki
AU  - Mao, Li
TI  - Oral Epithelium as a Surrogate Tissue for Assessing Smoking-Induced Molecular Alterations in the Lungs
AID  - 10.1158/1940-6207.CAPR-08-0058
DP  - 2008 Jun 01
TA  - Cancer Prevention Research
PG  - 39--44
VI  - 1
IP  - 1
4099  - http://cancerpreventionresearch.aacrjournals.org/content/1/1/39.short
4100  - http://cancerpreventionresearch.aacrjournals.org/content/1/1/39.full
SO  - Cancer Prev Res (Phila)2008 Jun 01; 1
AB  - 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.