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MDM2 Promoter SNP309 Is Associated with Risk of Occurrence and Advanced Lymph Node Metastasis of Nasopharyngeal Carcinoma in Chinese Population

Authors' Affiliations: ¹ Department of Genomics and Proteomics, Beijing Institute of Radiation Medicine; ² Department of Functional Genomics, Beijing Proteome Research Center; ³ Chinese National Human Genome Center at Beijing, Beijing, China; ⁴ Cancer Institute of Guangxi, Nanning, China; ⁵ Institute of Cancer Research, Nanfang Medical University, Guangzhou, China; and ⁶ Institute of Biomedical Sciences, Fudan University, Shanghai, China

Requests for reprints: Fuchu He or Gangqiao Zhou, Department of Genomics and Proteomics, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China. Phone/Fax: 86-10-68177417 or 86-10-80705255; E-mail: hefc{at}nic.bmi.ac.cn or zhougq{at}chgb.org.cn.

Purpose: Mouse double minute 2 (MDM2) is a key negative regulator of the p53 activity. Recently, a polymorphism in the MDM2 intronic promoter, SNP309, was shown to influence MDM2 expression and p53 activity. We examined whether the SNP309 was related to the risk of developing nasopharyngeal carcinoma (NPC) among Chinese populations.

Experimental Design: We genotyped the SNP309 in two independent case-control populations in southern China, one is from Guangxi province (including 593 NPC patients and 480 controls) and the other is from Guangdong province (including 239 patients and 286 controls), by PCR direct sequencing. Multivariate logistic regression analysis was used to calculate adjusted odds ratio (OR) and 95% confidence interval (95% CI).

Results: We observed that compared with the TT genotype, the genotypes containing G allele (GT + GG genotype) were associated with significant increased susceptibility to NPC in both Guangxi (OR, 1.43; 95% CI, 1.04-1.91) and Guangdong population (OR, 1.53; 95% CI, 1.00-2.36). When these two sample sets were combined, the OR of the GT + GG genotype developing NPC was 1.45 (95% CI, 1.12-1.85) compared with the TT genotype. Furthermore, compared with the TT genotype, the GT + GG genotype was also significantly associated with the advanced lymph node metastasis (OR, 1.84; 95% CI, 1.09-3.05).

Conclusions: Our findings suggest that the MDM2 SNP309 may be a risk factor for the occurrence and advanced neck lymph node metastasis of NPC in Chinese population.

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