Role of an MDM4 polymorphism in the early age of onset of nasopharyngeal carcinoma

Zhang,Yao Wei; Guan,Jian; Zhang,Yong; Qiu,Yu Rong; Chen,Long Hua

doi:10.3892/ol.2012.630

Role of an MDM4 polymorphism in the early age of onset of nasopharyngeal carcinoma

Authors:
- Yao Wei Zhang
- Jian Guan
- Yong Zhang
- Yu Rong Qiu
- Long Hua Chen
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Affiliations: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P.R. China, Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P.R. China, Department of Radiation Oncology, the First Affiliated Hospital of Kunming Medical College, Kunming 650031, P.R. China, Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P.R. China
Published online on: March 2, 2012 https://doi.org/10.3892/ol.2012.630
Pages: 1115-1118

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Abstract

Mouse double minute 4 (MDM4) is a critical negative regulator of the tumor suppressor p53. The results of studies have revealed that an MDM4 polymorphism (rs1563828) may contribute to the earlier onset of several malignant diseases. However, the correlation between this polymorphism and nasopharyngeal carcinoma (NPC) susceptibility has not been explored. We performed a case-control study with 210 NPC patients and 200 healthy controls. Significant associations were found when comparing the age of onset of NPC according to the rs1563828 genotype (P=0.01). The average age of onset of NPC in patients with the TT, CC and CT genotypes was 39.3, 48.2 and 45.5 years, respectively. Homozygous variant (TT) carriers developed NPC at an earlier age than homozygous (CC) carriers, such that the age of onset was accelerated by 8.9 years (P=0.002). Our data suggest that rs1563828 is a modifier of the age of onset of NPC in the population studied. The age of onset for NPC with TT homozygotes was earlier than CC carriers.

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1	Wei KR, Yu YL, Yang YY, Ji MF, Yu BH, Liang ZH and Reng X: Epidemiological trends of nasopharyngeal carcinoma in China. Asian Pac J Cancer Prev. 11:29–32. 2010.PubMed/NCBI
2	Zhou G, Zhai Y, Cui Y, Zhang X, Dong X, Yang H, He Y, Yao K, Zhang H, Zhi L, et al: MDM2 promoter SNP309 is associated with risk of occurrence and advanced lymph node metastasis of nasopharyngeal carcinoma in Chinese population. Clin Cancer Res. 13:2627–2633. 2007. View Article : Google Scholar : PubMed/NCBI
3	Li Y, Fu L, Wong AM, Fan YH, Li MX, Bei JX, Jia WH, Zeng YX, Chan D, Cheung KM, et al: Identification of genes with allelic imbalance on 6p associated with nasopharyngeal carcinoma in southern Chinese. PLoS One. 6:e145622011. View Article : Google Scholar : PubMed/NCBI
4	Xiao M, Zhang L, Zhu X, Huang J, Jiang H, Hu S and Liu Y: Genetic polymorphisms of MDM2 and TP53 genes are associated with risk of nasopharyngeal carcinoma in a Chinese population. BMC Cancer. 10:1472010. View Article : Google Scholar : PubMed/NCBI
5	Yu H, Huang YJ, Liu Z, Wang LE, Li G, Sturgis EM, Johnson DG and Wei Q: Effects of MDM2 promoter polymorphisms and p53 codon 72 polymorphism on risk and age at onset of squamous cell carcinoma of the head and neck. Mol Carcinog. 50:697–706. 2011. View Article : Google Scholar : PubMed/NCBI
6	Markey MP: Regulation of MDM4. Front Biosci. 16:1144–1156. 2011. View Article : Google Scholar : PubMed/NCBI
7	Yu H, Wang LE, Liu Z, Wei S, Li G, Sturgis EM and Wei Q: Polymorphisms of MDM4 and risk of squamous cell carcinoma of the head and neck. Pharmacogenet Genomics. 21:388–396. 2011. View Article : Google Scholar : PubMed/NCBI
8	Kulkarni DA, Vazquez A, Haffty BG, Bandera EV, Hu W, Sun YY, Toppmeyer DL, Levine AJ and Hirshfield KM: A polymorphic variant in human MDM4 associates with accelerated age of onset of estrogen receptor negative breast cancer. Carcinogenesis. 30:1910–1915. 2009. View Article : Google Scholar : PubMed/NCBI
9	Fang S, Krahe R, Lozano G, Han Y, Chen W, Post SM, Zhang B, Wilson CD, Bachinski LL, Strong LC and Amos CI: Effects of MDM2, MDM4 and TP53 codon 72 polymorphisms on cancer risk in a cohort study of carriers of TP53 germline mutations. PLoS One. 5:e108132010. View Article : Google Scholar : PubMed/NCBI
10	Huang SF, Chen IH, Liao CT, Wang HM, Liou SH and Hsieh LL: Combined effects of MDM2 SNP 309 and p53 mutation on oral squamous cell carcinomas associated with areca quid chewing. Oral Oncol. 45:16–22. 2009. View Article : Google Scholar : PubMed/NCBI
11	Toledo F and Wahl GM: MDM2 and MDM4: p53 regulators as targets in anticancer therapy. Int J Biochem Cell Biol. 39:1476–1482. 2007. View Article : Google Scholar : PubMed/NCBI
12	Ménendez S, Goh AM, Camus S, Ng KW, Kua N, Badal V and Lane DP: MDM4 downregulates p53 transcriptional activity and response to stress during differentiation. Cell Cycle. 10:1100–1108. 2011.PubMed/NCBI
13	Mancini F, Gentiletti F, D’Angelo M, Giglio S, Nanni S, D’Angelo C, Farsetti A, Citro G, Sacchi A, Pontecorvi A and Moretti F: MDM4 (MDMX) overexpression enhances stabilization of stress-induced p53 and promotes apoptosis. J Biol Chem. 279:8169–8180. 2004. View Article : Google Scholar : PubMed/NCBI
14	Atwal GS, Kirchhoff T, Bond EE, Montagna M, Menin C, Bertorelle R, Scaini MC, Bartel F, Bohnke A, Pempe C, et al: Altered tumor formation and evolutionary selection of genetic variants in the human MDM4 oncogene. Proc Natl Acad Sci USA. 106:10236–10241. 2009. View Article : Google Scholar : PubMed/NCBI
15	Nichols HB, Trentham-Dietz A, Hampton JM, Titus-Ernstoff L, Egan KM, Willett WC and Newcomb PA: From menarche to menopause: trends among US Women born from 1912 to 1969. Am J Epidemiol. 164:1003–1011. 2006. View Article : Google Scholar : PubMed/NCBI
16	Chang ET and Adami HO: The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev. 15:1765–1777. 2006. View Article : Google Scholar : PubMed/NCBI
17	Tse KP, Su WH, Yang ML, Cheng HY, Tsang NM, Chang KP, Hao SP, Yao SY and Chang YS: A gender-specific association of CNV at 6p21.3 with NPC susceptibility. Hum Mol Genet. 20:2889–2896. 2011. View Article : Google Scholar
18	Suda T, Yoshihara M, Nakamura Y, Sekiguchi H, Godai TI, Sugano N, Tsuchida K, Shiozawa M, Sakuma Y, Tsuchiya E, et al: Rare MDM4 gene amplification in colorectal cancer: The principle of a mutually exclusive relationship between MDM alteration and TP53 inactivation is not applicable. Oncol Rep. 26:49–54. 2011.PubMed/NCBI