%0 Journal Article
%T Implication of DNA Methylation Profiling in Oral Epithelium for Lung Cancer Screening
%A Hiroaki Harada
%A Kazuaki Miyamoto
%A Yoshinori Yamashita
%A Kikuo Nakano
%A Kiyomi Taniyama
%A Masami Kimura
%A Yoshihiro Miyata
%A Hideki Ohdan
%A Morihito Okada
%J ISRN Pulmonology
%D 2012
%R 10.5402/2012/973203
%X In lung cancer, the roles of molecular alterations in blood, sputum, bronchial brushing, and exhaled gas samples, which are relatively easy to obtain, have been evaluated for clinical availability. This study was based on the hypothesis that similar molecular alterations occur in the lung and oral cavity because both are exposed to the same environmental or tobacco-derived carcinogens. Because epigenetic alterations due to exposure to carcinogens are thought to play a major role in the development of lung cancer, the DNA methylation status of 11 genes in the oral epithelium was analyzed in lung cancer patients ( ) and control individuals without lung cancer ( ). DNA methylation profiling revealed that GDNF, RARB, and HS3ST2 were methylated more frequently in cancer patients than in the control participants ( , 0.0062, and 0.0193, resp.). Combined analysesindicatedthat 6 of 16 cancer patients (37.5%), but only 1 of 32 control individuals (3.1%) showed DNA methylation in 2-3 of these 3 genes ( ). These combined analyses showed the high specificity and positive predictive value in total and subgroup analyses. Our data suggest that DNA methylation profiling using oral epithelium may help in the identification of individuals with a high risk of lung cancer. 1. Introduction Lung cancer is the leading cause of cancer-related death in many countries [1]. A major factor contributing to this high mortality is that most tumors are not diagnosed until an advanced stage [2]. Although a variety of investigations and screening programs for early detection of lung cancer have been conducted, each approach has lacked diagnostic specificity [3, 4]. Recent reports indicated that screening using low-dose computed tomography (CT) showed encouraging results in reducing lung cancer mortality in patients with a history of cigarette smoking of at least 30 packs per year [5]. However, the frequency of lung cancer in that screening program was considerably low, although the participants were limited to individuals with a heavy smoking history. These results indicate that identification of individuals with a high risk of lung cancer is important for improving the specificity and reliability of lung cancer screening programs. Inhaled carcinogens from tobacco smoke, workplace agents, and other environmental factors such as air pollution are well known to be among the main etiological factors that cause molecular alterations in lung cancer pathogenesis [6], and the predisposition of smokers to epigenetic alterations has been characterized [7¨C9]. Because gene promoter methylation is a
%U http://www.hindawi.com/journals/isrn.pulmonology/2012/973203/