• BMB Reports
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• v.40 no.2
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• pp.142-150
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• 2007

Epigenetic alterations, represented by aberrant DNA methylation, are deeply involved in human cancers. In gastric cancers, tumor-suppressor genes are inactivated more frequently by promoter methylation than by mutations. We recently showed that H. pylori infection, a potent gastric carcinogenic factor, induces methylation of specific genes in the gastric mucosae. When the methylation levels were analyzed in the gastric mucosae of healthy volunteers, cases with a single gastric cancer, and cases with multiple gastric cancers, who have increasing levels of risks for gastric cancers, there was a significant increasing trend in the methylation levels among the individuals without current H. pylori infection. This finding unequivocally showed the presence of an epigenetic field for cancerization. The degree of the field defect was measured more conveniently using methylation levels of marker genes than using those of tumor-suppressor genes. The presence of an epigenetic field for cancerization has been indicated for liver, colon, Barrett's esophageal, lung, breast, and renal cancers. Since decreased transcription is involved in the specificity of methylated genes, it is likely that specific genes are methylated according to carcinogenic factors. These findings emphasize the usefulness of DNA methylation as a marker for past exposure to carcinogens and future risk of cancer development.

• Korean Journal of Bronchoesophagology
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• v.3 no.2
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• pp.226-233
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• 1997

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2225-2229
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• 2014

Background: Carcinoma of the tongue is the most common intra-oral malignancy in Western countries. Incidence and mortality rates have increased in recent years, and survival has not improved. This study aimed to determine etiologic factors for tongue cancer with age-sex matched case-control data. Materials and Methods: 47 patients with carcinoma of the tongue referred to our oral medicine clinic between years 2005-2006 were analyzed and compared with control group data. The medical records, including family history of cancer, dental trauma, and history of abuse of alcohol and tobacco products was recorded for all subjects. Chi square comparison tests and linear regression analysis were performed using the SPSS program for statistics. Results: Patient and randomly selected control groups each consisted of 30 male and 17 female subjects with mean ages 53.2 (${\pm}12.6$) and 52.6 (${\pm}11.5$) years respectively. Smoking and alcohol abuse proportions were significantly higher in the patient group (p=0.0001, p<0.0001 respectively). Chronic mechanical trauma was observed in 44.7% of the patients and 17.0% of the control group (p=0.004). Similarly, family history of cancer of any type (for the first degree relatives) was found to be more common in the patient group (p=0.009). On regression analysis, alcohol abuse, family history of cancer, smoking, chronic mechanical traumas appeared as significant etiologic factors (p=0.0001). Conclusions: We believe that field cancerization may become evident in oral and oropharyngeal mucosa with multiple steps of molecular changes starting from the first sign of dysplasia with chronic exposure to etiological factors. Chronic trauma cases need particular attention to search for very early signs of cancer.

• Tuberculosis and Respiratory Diseases
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• v.41 no.3
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• pp.277-288
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• 1994

Objectives : Multiple lung cancers and/or precancerous lesions can be developed because many bronchi are exposed to carcinogens simultaneously according to the concept of "Field Cancerization". We had performed a careful bronchoscopic examination and analysed the patients of double bronchial lesions who received the separate pathologic evaluation. Methods : We studied 21 patients of double bronchial lesions among 1855 patients of bronchoscopic examination from April 1990 to December 1993 in Korea Cancer Center Hospital. We classified the patients into three groups(double malignancies of different histology, double malignancies of same histology, and combination of malignant and benign lesions) and analysed the histologic type, location, radiologic findings, and clinical parameters. Results : Among 21 patients, six patients had double malignancies of different histology, eight had double malignancies of same histology, and seven had combination of malignant and benign lesions. Out of 14 double malignant cases, 11 cases are considered as synchronous multiple primary lung cancers. Combination of squamous cell carcinomas was found in 5 cases, combination of small cell carcinoma and squamous cell carcinoma was found in 4 cases. Combination of adenocarcinoma and squamous cell carcinoma and combination of squamous cell carcinoma and poorly differentiated carcinoma were found in 1 case respectively. All patients of synchtonous multiple primary lung cancers were male and had long smoking history(average 40 pack years). Among 21 cases of double bronchial lesions, only one lesion could be detected by prebronchoscopic radiologic examination including chest CT in 15 cases. Conclusions : The presence of double bronchial lesions including multiple primary lung cancers and the limitation of radiologic examination to detect early bronchial lesions encourage us to examine the whole bronchi carefully and to perform pathologic evaluations.

• Journal of Oral Medicine and Pain
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• v.30 no.3
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• pp.301-317
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• 2005

The number of patients with tongue carcinoma is increasing rapidly among young individuals in many parts of the world. Oral carcinoma progresses from hyperplastic lesion through dysplasia to invasive carcinoma and the concept of "field cancerization" with molecular alteration has been suggested for oral cavity carcinogenesis. Significant improvement in treatment and prognosis will depend on more detailed understanding of the multi-step process leading to cancer development. To induce tongue carcinoma in rat by 4-NQO, each drinking water was made to 10 ppm, 25 ppm, 50 ppm and control (only D.W. without 4-NQO). Specimens were classified into 4 groups such as control, I (mild & moderate dysplasia), II (severe dysplasia and carcinoma in situ), III (carcinoma). The mRNA expressions of Bcl-2 family were evaluated by RT-PCR technique. For anti-apoptotic Bcl-2 family, mRNA expression of Bcl-w was down-regulated in all stages of tongue carcinogenesis model. However, mRNA expression of Bcl-2 was up-regulated. For pro-apoptotic Bcl-2 family, all members were down-regulated in all stages of tongue carcinogenesis model except for Bad mRNA in group III. In terms of BH3 only protein, mRNA expressions of Bok and Mcl-1 were down regulated in all stages of specimen, but Bmf in group II and BBC3 in group III were up-regulated. Our current findings demonstrated the involvements of mRNA expression of Bcl-2 family in multi-step tongue carcinogensis. This highlights the necessity for continued efforts to discover suitable biomakers (Bcl-2 family) for early diagnosis of the disease, and to understand its pathogenesis as a first step in improving methods of treatment. The discovery of these potential biomarkers and molecular targets for cancer diagnostics and therapeutics has the potential to significantly change the clinical approach and outcome of the disease.