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인슐린양 성장 인자 결합 단백-3 유전자 -202 좌위의 다형성에 따른 비소세포폐암의 의험도

Promoter -202 A/C Polymorphism of Insulin-like Growth Factor Binding Protein-3 Gene and Non-small Cell Lung and Non-small Cell Lung Cancer Risk

Tuberculosis & Respiratory Diseases / Tuberculosis & Respiratory Diseases,
2005, v.58 no.4, pp.359-366
문진욱 (연세대학교)
장윤수 (대진대학교)
김성규 (연세대학교)
김희정 (연세대학교)
박무석 (연세대학교)
김영삼 (연세대학교)
장준 (연세대학교)
김세규 (연세대학교)
한창훈 (연세대학교)
강신명 (연세대학교)
변민광 (연세대학교)
정우영 (연세대학교)
박재준 (연세대학교)
유경남 (연세대학교)
신주혜 (연세대학교)
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초록

인슐린양 성장 인자 결합 단백-3(Insulin-like growth factor (IGF) binding protein-3 (IGFBP-3))는 혈액 내에서 IGF와 결합하여 복합체 혹은 저장소로 작용함으로써, IGF가 수용체에 결합하는 것을 방해하여 IGF의 항세포사멸(anti- apoptosis) 및 세포분열 촉진의 기능을 억제한다. 하지만, 특정 상황에서는 도리어 IGFBP-3가 IGF의 파괴를 억제하여 IGF에 의한 암세포의 분화 및 성장을 촉진할 수도 있다는 것이 알려져 있다. 대부분의 환자에서 혈액내 IGFBP-3 수치는 IGFBP-3 유전자의 -202 좌위(locus)의 다형성(polymorphism)에 의해 크게 영향을 받는다. 따라서, 저자 등은 제한 효소(restriction enzyme)를 이용하여 비소세포폐암 환자의 IGFBP-3 유전자 -202 좌위의 다형성을 분석함으로써, 이 좌위의 다형성이 비소세포폐암의 위험도와 연관되어 있는지 조사하였다. 본 연구는 104명의 비소세포폐암 환자군과, 연령, 성별, 흡연력이 비슷한 104명의 대조군을 비교 분석하였다. 대조군에서 -202 좌위 유전자 다형성의 빈도는 AA형 48명 (46.2%), AC형 45명 (43.3%), CC형 11명 (10.5%)이었고, 비소세포폐암 환자군에서 -202 좌위 유전자 다형성의 빈도는 AA형 67명 (64.4%), AC형 35명 (33.7%), CC형 2명 (1.9%)이었다. -202 좌위의 유전자 다형성에 있어서 대조군과 비소세포폐암 환자군 사이에 유의한 빈도 차이가 있었으며 (p < 0.05, Pearson’s χ2test), 비소세포폐암의 위험도는 -202 좌위의 AA형에서 가장 높고 CC형에서 가장 낮았다. CC형을 기준으로 하면 AC형의 비교 위험도는 2.60 (95% 신뢰구간: 0.89 - 8.60)이었으며 AA형의 비교 위험도는 5.89 (95% 신뢰구간: 1.92 - 21.16)이었다. 본 연구 결과는, IGFBP-3 유전자의 -202 좌위(locus)의 다형성(polymorphism)이 비소세포폐암의 위험인자 중의 하나일 가능성을 제시하며, 따라서 비소세포폐암에 대한 항암치료 개발에 있어서 새로운 표적이 될 가능성을 시사한다. (Tuberc Respir Dis 2005; 58: 359-366)

keywords
Insulin-like growth factor (IGF), Insulin-like growth factor binding protein-3 (IGFBP-3), Non-small cell lung cancer (NSCLC), Promoter -202 A/C polymorphism, Restriction fragment length polymorphism (RFLP)

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