[논문]한국인에서 Myeloperoxidase (MPO) 유전자의 -463G>A 다형성과 원발성 폐암의 위험도

박재형; 박정민; 김은진; 윤석진; 이승준; 차승익; 이응배; 김창호; 감신; 김동선; 정태훈; 박재용

doi:10.4046/trd.2005.59.2.157

[국내논문] 한국인에서 Myeloperoxidase (MPO) 유전자의 -463G>A 다형성과 원발성 폐암의 위험도
Myeloperoxidase -463G>A Polymorphism dose not Contribute to the Risk of Primary Lung Cancer in a Korean Population 원문보기

Tuberculosis and respiratory diseases : TRD = 결핵 및 호흡기 질환, v.59 no.2 = no.247, 2005년, pp.157 - 163

초록
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목 적 : Myeloperoxidase (MPO)는 benzo(a)pyrene, aromatic amines과 같은 발암전구물질 활성화를 통해 폐암 발생에 관여한다. MPO 유전자 promoter 부위의 -463G>A 다형성은 MPO유전자의 발현량을 감소시킨다고 알려져 있다. 저자들은 MPO 유전자 promoter 부위의 -463G>A 다형성과 폐암 위험도의 상관 관계를 조사하였다. 방 법 : 경북대학교병원에서 폐암으로 진단된 432예를 대상으로 하였으며 대조군은 건강검진센타를 방문한 건강인 가운데 환자군과 연령 및 성을 match하여 무작위로 선택한 432명을 대상으로 하였다. 결 과 : MPO -463G>A의 유전자형은 폐암군의 경우 GG, GA, AA형이 각각 353명(81.7%), 76명(17.6%), 3명(0.7%)이였고 대조군의 경우 각각 356명(82.4%), 72명(16.7%), 4명(0.9%)으로 두 군간에 유의한 차이가 없었다. -463 AA+GA 유전자형은 -463 GG 유전자형에 비해 전체 폐암의 경우 위험도의 유의한 차이가 없었으며 (adjusted OR= 1.03, 95% CI= 0.72-1.47), 연령, 성별, 흡연력, 조직형으로 구분하였을 경우에도 유의한 차이가 없었다. 결 론 : MPO 유전자의 -463G>A 다형성은 한국인에서 폐암의 위험도를 결정하는 주요 인자가 아닌 것으로 생각된다.

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제안 방법

A detailed questionnaire was completed for each patient and control by a trained interviewer. The questionnaire included information on the average number of cigarettes smoked daily and the number of years the subjects had been smoking. For smoking status, a person who had smoked at least once a day for > 1 year in his or her lifetime was regarded as a smoker.
Hardy-Weinberg equilibrium was tested with a goodness-of-fit x² test with one degree of freedom for the comparing the observed genotype frequencies with the expected genotype frequencies among the subjects. Unconditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment for the possible confounders (gender as a nominal variable; age and pack-years of smoking, as continuous variables). The ORs were calculated as the combined AA + GA genotype relative to the GG genotype since the number of homozygous variant AA genotype was small among the cases and controls.

대상 데이터

There were no age, gender, histological or stage restrictions, but patients with a prior history of cancers were excluded from this study. The cases included 210 (48.6%) squamous cell carcinomas, 141 (32.6%) adenocarcinomas, 73 (16.9%) small cell carcinomas, and 8 (1.9%) large cell carcinomas. The demographics and clinical characteristics of the cases were consistent with those of a nationwide lung cancer survey conducted by the Korean Academy of Tuberculosis and Respiratory Disease in 1998¹².
The demographics and clinical characteristics of the cases were consistent with those of a nationwide lung cancer survey conducted by the Korean Academy of Tuberculosis and Respiratory Disease in 1998¹². The control subjects were randomly selected from a pool of healthy volunteers who visited the general health check-up center at Kyungpook National University Hospital during the same period. The control subjects were frequency matched (1:1) to the cancer cases based on gender and age (± 5 years).
The control subjects were frequency matched (1:1) to the cancer cases based on gender and age (± 5 years). All the cases and the controls were ethnic Koreans and they resided in Daegu City or the surrounding regions. A detailed questionnaire was completed for each patient and control by a trained interviewer.

데이터처리

Cases and controls were compared using the Student's t-test for continuous variables and the x² test for categorical variables. Hardy-Weinberg equilibrium was tested with a goodness-of-fit x² test with one degree of freedom for the comparing the observed genotype frequencies with the expected genotype frequencies among the subjects.
test for categorical variables. Hardy-Weinberg equilibrium was tested with a goodness-of-fit x² test with one degree of freedom for the comparing the observed genotype frequencies with the expected genotype frequencies among the subjects. Unconditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment for the possible confounders (gender as a nominal variable; age and pack-years of smoking, as continuous variables).

성능/효과

About 10% of the samples were then randomly genotyped again by a different author, and the results were 100% concordant. To confirm the genotyping results, selected PCR-amplified DNA samples (n = 2, respectively, for each genotype) were examined by DNA sequencing, and the results were also 100% concordant.
Unconditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment for the possible confounders (gender as a nominal variable; age and pack-years of smoking, as continuous variables). The ORs were calculated as the combined AA + GA genotype relative to the GG genotype since the number of homozygous variant AA genotype was small among the cases and controls. Multiple logistic regression analyses were performed to analyze the association between the genotypes and risk of lung cancer after stratification into age (median age, ≤62 years/>62 years), gender, smoking status, cigarette consumption (median pack-years, ≤40 pack-years/>40 packyears) and histological types of lung cancer.
47). When the analyses were stratified by age, gender, smoking status, and pack-years of smoking, no significant association was found between the genotypes and risk of lung cancer. Moreover, the genotypes exhibited no apparent relationship with any of histological types of lung cancer.
The frequency of the -463A allele among the healthy controls in this study was significantly lower (P < 0.05) than those of Japanese (0.169; Ref. 7)), Chinese (0.155; Ref. 8), Caucasians (0.204-0.259; Refs. 4-7 and 13) and African-Americans (0.299; Ref. 13).
For overall lung cancers, this study had 80% power (two-sided test of significance, α = 0.05) to detect an OR < 0.58 (assuming a protective effect) or an OR > 1.59 (assuming a risk effect) for the carriers of -463 AA or GA genotype relative to the carriers of -463 GG genotype. Because of the low prevalence of the -463 AA genotype, we combined this genotype with the heterozygous -463 GA genotype into one group.

참고문헌 (19)

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상세보기
Piedrafita FJ, Molander RB, Vansant G, Orlova EA, Pfahl M, Reynolds WF. An Alu element in the myeloperoxidase promoter contains a composite SP1-thyroid hormone-retinoic acid response element. J Biol Chem 1996;271:14412-20

상세보기
van Schooten FJ, Boots AW, Knaapen AM, Godschalk RW, Maas LM, Borm PJ, et al. Myeloperoxidase (MPO) -463G->A reduces MPO activity and DNA adduct levels in bronchoalveolar lavages of smokers. Cancer Epidemiol Biomarkers Prev 2004;13:828-33
Feyler A, Voho A, Bouchardy C, Kuokkanen K, Dayer P, Hiroven A, et al. Myeloperoxidase -463 G -> a polymorphism and lung cancer risk. Cancer Epidemiol Biomarkers Prev 2002;11:1550-4
Xu LL, Liu G, Miller DP, Zhou W, Lynch TJ, Wain JC, et al. The myeloperoxidase -463 G -> a polymorphism does not decrease lung cancer susceptibility in Caucasians. Cancer Epidemiol Biomarkers Prev 2002;11:1555-9
Dally H, Gassner K, Jager B, Schmezer P, Spiegelhalder B, Edler L, et al. Myeloperoxidase (MPO) genotype and lung cancer histologic types: the MPO-463 a allele is associated with reduced risk for small cell lung cancer in smokers. Int J Cancer 2002;102:530-5

상세보기
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Lee SJ, Lee SY, Jeon HS, Park SH, Jang JS, Lee GY, et al. Vascular endothelial growth factor gene polymorphisms and risk of primary lung cancer. Cancer Epidemiol Biomarkers Prev 2005;14:571-5

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Misra RR, Tangrea JA, Virtamo J, Ratnasinghe D, Andersen MR, Barrett M, et al. Variation in the promoter region of the myeloperoxidase gene is not directly related to lung cancer risk among male smokers in Finland. Cancer Lett 2001;164:161-7

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Chevrier I, Stucker I, Houllier AM, Cenee S, Beaune P, Laurent-Puig P, et al. Myeloperoxidase: new polymorphisms and relation with lung cancer risk. Pharmacogenetics 2003;13:729-39

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Cascorbi I, Henning S, Brockmoller J, Gephart J, Meisel C, Miller JM, et al. Substantially reduced risk of cancer of the aerodigestive tract in subjects with variant -463A of the myeloperoxidase gene. Cancer Res 2000;60:644-9

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저자의 다른 논문 :

표제어: PCR

동의어: Packet Collision Rate

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용어 설명: PCR은 세균 특이성이 있는 primer를 이용하여 적은 수의 세균이 있을지라도 쉽게 검출할 수 있는 유용한 방법이며, 이를 이용하여 구강 내 치면세균막이나 타액에서 직접 세균을 검출할 수 있게 되었다[8].

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