MDM2 309T>G polymorphism and risk of lung cancer in a Korean population

被引:35
作者
Park, Sun Ha
Choi, Jin Eun
Kim, Eun Jin
Jang, Jin Sung
Han, Hyung Soo
Lee, Won Kee
Kang, Young Mo
Park, Jae Yong
机构
[1] Kyungpook Natl Univ Hosp, Dept Internal Med, Taegu 700412, South Korea
[2] Kyungpook Natl Univ Hosp, Canc Res Inst, Taegu 700412, South Korea
[3] Kyungpook Natl Univ Hosp, Dept Biochem, Taegu 700412, South Korea
[4] Kyungpook Natl Univ, Sch Med, Dept Physiol, Taegu 700422, South Korea
[5] Kyungpook Natl Univ, Sch Med, Dept Prevent Med, Taegu 700422, South Korea
关键词
MDM2; polymorphism; lung cancer; genetic susceptibility;
D O I
10.1016/j.lungcan.2006.06.008
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: The MDM2 protein plays an important role in regulating cell. proliferation and apoptosis by interaction with multiple proteins including p53 and Rb. A polymorphism (309T>G) in the MDM2 promoter has been shown to result in higher levels of MDM2 RNA and protein. In order to evaluate the association of the MDM2 309T>G polymorphism and lung cancer risk, we carried out a case-control study in a Korean population. Methods: The MDM2 genotypes were determined in 582 Lung cancer patients and in 582 healthy control subjects who were frequency matched for age and gender. Results: The distribution of the MDM2 309T>G genotypes was not significantly different between overall lung cancer cases and controls. However, when the cases were categorized by tumor histotogy, the 309GG genotype was associated with a significantly increased risk of adenocarcinoma (adjusted OR= 1.91, 95% Cl = 1.16-3.14, P= 0.01) compared to the 309TT genotype. In addition, the risk of adenocarcinoma increased as the number of 309G alleles increased (P-trend = 0.01). Conclusion: Our findings suggest that the MDM2 309T>G polymorphism may be used as a marker for genetic susceptibility to adenocarcinoma of the lung. (C) 2006 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:19 / 24
页数:6
相关论文
共 35 条
[1]  
Aikawa H, 2000, INT J MOL MED, V5, P631
[2]   The MDM2 promoter polymorphism SNP309T→G and the risk of uterine leiomyosarcoma, colorectal cancer, and squamous cell carcinoma of the head and neck [J].
Alhopuro, P ;
Ylisaukko-oja, SK ;
Koskinen, WJ ;
Bono, P ;
Arola, J ;
Järvinen, HJ ;
Mecklin, JP ;
Atula, T ;
Kontio, R ;
Mäkitie, AA ;
Suominen, S ;
Leivo, I ;
Vahteristo, P ;
Aaltonen, LM ;
Aaltonen, LA .
JOURNAL OF MEDICAL GENETICS, 2005, 42 (09) :694-698
[3]   A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans [J].
Bond, GL ;
Hu, WW ;
Bond, EE ;
Robins, H ;
Lutzker, SG ;
Arva, NC ;
Bargonetti, J ;
Bartel, F ;
Taubert, H ;
Wuerl, P ;
Onel, K ;
Yip, L ;
Hwang, SJ ;
Strong, LC ;
Lozano, G ;
Levine, AJ .
CELL, 2004, 119 (05) :591-602
[4]   O6-alkylguanine-DNA alkyltransferase gene polymorphisms and the risk of primary lung cancer [J].
Chae, MH ;
Jang, JS ;
Kang, HG ;
Park, JH ;
Park, JM ;
Lee, WK ;
Kam, S ;
Lee, EB ;
Son, JW ;
Park, JY .
MOLECULAR CARCINOGENESIS, 2006, 45 (04) :239-249
[5]   Mdm2 overexpression and p14ARF inactivation are two mutually exclusive events in primary human lung tumors [J].
Eymin, B ;
Gazzeri, S ;
Brambilla, C ;
Brambilla, E .
ONCOGENE, 2002, 21 (17) :2750-2761
[6]   Functions of the MDM2 oncoprotein [J].
Freedman, DA ;
Wu, L ;
Levine, AJ .
CELLULAR AND MOLECULAR LIFE SCIENCES, 1999, 55 (01) :96-107
[7]   Population aspects of cancer genetics [J].
Goldgar, DE .
BIOCHIMIE, 2002, 84 (01) :19-25
[8]   The role of P53 and MDM2 polymorphisms in the risk of esophageal squamous cell carcinoma [J].
Hong, Y ;
Miao, XP ;
Zhang, XM ;
Ding, F ;
Luo, AP ;
Guo, YL ;
Tan, W ;
Liu, ZH ;
Lin, DX .
CANCER RESEARCH, 2005, 65 (20) :9582-9587
[9]   Detecting low penetrance genes in cancer: the way ahead [J].
Houlston, RS ;
Tomlinson, IPM .
JOURNAL OF MEDICAL GENETICS, 2000, 37 (03) :161-167
[10]   RB regulates the stability and the apoptotic function of p53 via MDM2 [J].
Hsieh, JK ;
Chan, FSG ;
O'Connor, DJ ;
Mittnacht, S ;
Zhong, S ;
Lu, X .
MOLECULAR CELL, 1999, 3 (02) :181-193