한국인과 중국 연변지역의 조선족에서 hOGG과 L-myc 그리고 대사효소 등의 다형성과 흡연 및 음주가 폐암발생에 미치는 영향에 대한 비교연구
A Comparative Study on the Effects of Genetic Factors, Smoking and Alcohol Intake on Lung Cancer in Koreans and Korean-Chinese
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초록
연구배경폐암은 한국에서 두 번째로 흔한 암종으로 한국인과 중국 연변지역 조선족의 폐암 사망률이 다르다. 본 연구는 폐암과 관련된 것으로 알려진 여섯 가지 유전자인 cytochrome P450 1A1(CYP1A1)과 cytochrome P450 2E1(CYP2E1), 그리고 glutathione S-transferase mu(GSTM1)와 theta(GSTT1), 8-hydroxyguanine glycosylase(hOGG1), L-myc protooncogene, 환경적 요인등이 한국인과 중국 거주 조선족의 폐암에 미치는 영향을 규명하고자 수행되었다. 방 법한국인 폐암환자 114명과 대조군 115명, 중국 거주 조선족 폐암환자 68명과 대조군 57명을 모집하여 환자-대조군 연구로 수행하였다. 설문조사로 인적사항과 환경적 요인을 조사하였고, 정맥혈에서 DNA를 추출하여 CYP1A1과 CYP2E1 그리고 GSTM1, GSTT1, hOGG1, L-myc 유전자 유형을 분석하였다. 결 과한국인에서 GSTT1 유전자가 결손인 경우 폐암의 대응위험도가 3.1(1.8-5.4)로 통계적으로 유의하게 높았다. CYP1A1 유전자가 Val/Val 형인 경우 Ile/Ile 형에 비해 대응위험도가 0.14(0.05, 0.40)로 유의하게 낮았다. GSTT1과 CYP1A1은 다변량분석에서도 폐암과 유의한 관련성을 보였다. 나머지 유전자형은 폐암과 유의한 관련성을 보이지 않았다. 중국 거주 조선족에서 다변량분석결과 hOGG1과 L-myc 유전자가 폐암과 유의한 관련성을 보여 한국인과 조선족에서 폐암과 관련된 유전자 유형이 다른 것으로 나타났다. 흡연은 한국인과 조선족 모두에서 유의하게 폐암을 증가시키는 것으로 재확인되었다. 결 론이러한 결과는 유전적 요인이 동일하더라도 한국과 중국에서 폐암 발생에 영향을 미치는 유전자가 상이하여 강한 유전자-환경요인의 상호작용이 존재함을 시사하는 것이다
Abstract
Background Lung cancer is the second most frequent cancer in Korea. The mortality of lung cancer is different in Korean- Chinese. This study was aimed to evaluate the effects of six genes, cytochrome P450 1A1(CYP1A1), cytochrome P450 2E1(CYP2E1), glutathione S-transferase mu(GSTM1) and theta(GSTT1), 8-hydroxyguanine glycosylase(hOGG1), and L-myc protooncogene, and environmental factors on lung cancer in Koreans and, Korean-Chinese. Methods One hundred and fourteen Korean lung cancer patients, and 115 Korean controls who were recruited at Chungbuk National University Hospital, and 68 Korean-Chinese lung cancer patients and 57 Korean-Chinese controls who were at Yanbian University Hospital were included in this case-control study. After separating DNA from peripheral blood, genotypes of the CYP1A1, CYP2E1, GSTM1, GSTT1, hOGG1, and L-myc genes were analysed. Results In Koreans, the odds ratio(OR) of GSTT1 null genotype on lung cancer was 3.1(1.8-5.4), which was statistically significant. GSTM1 null type showed an odds ratio of 1.3(0.8-2.3). CYP2E1 and L-myc genotype showed no significant effect on the lung cancer risk. The risk of lung cancer was lower in Koreans with CYP1A1 Val/Val type than in those with the other CYP1A1 genotypes. In Korean-Chinese, polymorphisms of the hOGG1 and L-myc showed significant effects on lung cancer risk. Smoking showed a greater effect in Korean-Chinese than in Han-Chinese. The lung cancer related genes and smoking were different in Korean and Korean-Chinese. Conclusions These results imply that gene-environmental interaction shows a strong impact on the carcinogenegis of lung cancer in koreans and korean-chinese
참고문헌 (30)
- 김진복, "서울시 지역암등록 통계 1992-1995" (1998), 보건복지부
- 耿貫一, "流行病學第一版" (1979), 人民衛生出版社
- 김창길, "연길시 주민 사망원인에 관한 조사분석", 중국위생통계, 14, pp.36~37 (1997)
- 남홍매, "GSTM1과 GSTT1, 그리고 CYP1A1, CYP2E1 다형성이 폐암발생에 미치는 영향에 대한 환자-대조군연구", 대한예방의학회지, 32, pp.123~129 (1999)
- H Sugimura, "hOGG1 Ser326Cys polymorphism and Lung Cancer Susceptibility", Cancer Epidemiol Biomarkers Prev, 8, pp.669~674 (1999)
- K Kawashima, "Correlation of L-myc RFLP with metastasis, prognosis and multiple cancer in lung cancer patients", Int J Cancer, 50, pp.557~560 (1992)
- Alert Tobacco, "The tobacco epidemic: a global public health emergency" (1996), WHO
- J Seidegard, "Isoenzyme(s) of glutathione S-transferase(class Mu) as a marker for the susceptibility to lung cancer: a follow up study", pp.33~36 (1990), Carcinogenesis
- H Chen, "Increased risk for myelodysplastic syndromes in individuals with glutathione transferase theta 1(GSTT1) gene defect" (1996), Lancet
- TL Mclemore, "Expression of CYP1A1 gene in patients with lung cancer: evidence for cigarette smoke- induced gene expression in normal lung tissue and for pulmonary", J Natl Cancer Inst, 82, pp.1333~1339 (1990)
- S Kato, "Cytochrome p4502E1 genetic polymorphisms racial variation, and lung cancer risk", Cancer Res, 52, pp.6712~6715 (1992)
- K Masahiro, "Risk of smoking for spuamous and small cell carcinomas of the lung modulated by combinations of CYP1A1 and GSTM1 gene polymorphisms in a Japanese population", Carcinogenesis, 16, pp.2331~2336 (1985)
- K Nakachi, "Polymorphism of the CYP1A1 and glutathione S-transferase genes associated with susceptibility to lung cancer in relation to cigarette dose in a Japanese population", Cancer Res, 53, pp.2994~2999 (1993)
- 한국인의 ACE, TNF-β, APOE, VDR, EDH17B2, CYP1A1, GSTM1, GSTT1, NAT2, 그리고 ALDH2 유전자 유형분포에 대한 조사 연구, "김헌", 보건복지부 보건의료기술개발사업보고서, ~ (1999)
- T Kohno, "Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA", Oncogene, 25, pp.3219~3225 (1998)
- K Janssen, "DNA repair activity of 8-oxoguanine DNA glycosylase 1(OGG1) in human lymphocytes is not dependent on genetic polymorphism Ser326", Cys326, 2001, pp.9, 207~216
- J Xu, "Associations between hOGG1 sequence variants and prostate cancer susceptibility", Cancer Res, 15, pp.2253~2257 (2002)
- H Wikman, "hOGG1 polymorphism and loss of heterozygosity (LOH): significance for lung cancer susceptibility in a Caucasian population", Int J Cancer, 15, pp.923~927 (2000)
- T Hanaoka, "hOGG1 exon 7 polymorphism and gastric cancer in case-control studies of Japanese Brazilians and non-Japanese Brazilians", Cancer Lett, 10, pp.53~61 (2001)
- LJ Hardie, "The effect of hOGG1 and glutathione peroxidase I genotypes and 3p chromosomal loss on 8-hydroxydeoxyguanosine levels in lung cancer", Carcinogenesis, 21, pp.167~172 (2000)
- A Klungland, "Accumulation of premutagenic DNA lesions in mice defective in removal of oxidative base damage", Proc Natl Acad Sci, 9, pp.1330~1335 (1999)
- CM Shih, "Association of L-myc polymorphism with lung cancer susceptibility and prognosis in relation to age-selected controls and stratified cases", Lung Cancer, 36, pp.125~132 (2002)
- KA Zimmermann, "Differential expression of myc family genes during murine development", Nature, 319통권 : 780, pp.783~ (1986)
- AV Togo, "L-myc polymorphism in cancer patients, healthy blood donors and elderly, tumor-free individuals in Russia", Int J Cancer, 85, pp.747~750 (2000)
- G Chenevix-Trench, "Restirction fragment length polymorphism of L-myc and myb in human leukemia and lymphoma in relation to age-selected controls", Br J Cancer, 60, pp.872~874 (1989)
- J Young, "Association of the SS genotype of the L-myc gene and loss of 18q sequences with a worse clinical prognosis in colorectal cancers", Oncogene, 9, pp.1053~1056 (1994)
- A Weston, "Relationship of the L-myc DNA polymorphism and relation to metastasis in Norwegian lung cancer patients", Br J Cancer, 61, pp.809~812 (1990)
- M Chan-Yeung, "Lung cancer susceptibility and polymorphisms of glutathione S-transferase genes in Hong Kong", Lung Cancer, 45, pp.155~160 (2004)
- XR V, "CYP1A1 and GSTM1 polymorphisms in relation to lung cancer risk in Chinese women", Cancer Lett, 214통권 : 197, pp.204~ (2004)
- L Quinones, "CYP1A1, CYP2E1 and GSTM1 genetic polymorphisms: The effect of single and combined genotypes on lung cancer susceptibility in Chilean people", Cancer Lett, 174, pp.35~44 (2001)