This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jiang, R.-C. Articles by Zeng, Y.-X. Search for Related Content PubMed PubMed Citation Articles by Jiang, R.-C. Articles by Zeng, Y.-X.

A Functional Variant in the Transcriptional Regulatory Region of Gene LOC344967 Cosegregates with Disease Phenotype in Familial Nasopharyngeal Carcinoma

¹ State Key Laboratory of Oncology in Southern China; Departments of ² Experimental Research and ³ Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, China; and ⁴ Chinese National Human Genome Center at Shanghai, Shanghai, China

Requests for reprints: Yi-Xin Zeng, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China. Phone: 86-20-8734-3333; Fax: 86-20-8734-3295; E-mail: yxzeng{at}gzsums.edu.cn.

Nasopharyngeal carcinoma is a common malignancy in Southeast Asian countries, and genetic background is a well-known component of the complexity underlying its tumorigenic process. We have mapped a nasopharyngeal carcinoma susceptibility locus to chromosome 4p15.1-q12 in a previous linkage study on nasopharyngeal carcinoma pedigrees. In this study provided in this communication, we screened all the genes in this region, with a focus on exons, promoters, and the exon-intron boundary to identify nasopharyngeal carcinoma–associated mutations or functional variants. Importantly, we found a novel gene (LOC344967) with a single nucleotide polymorphism –32G/A in the promoter region. This gene is a member of the acyl CoA thioesterase family that plays an important role in fatty acid metabolism and is involved in the progression of various types of tumors. The –32A variant was found cosegregated with the disease phenotype in the nasopharyngeal carcinoma pedigrees that we previously used for the linkage study. Moreover, this –32A variant creates an activator protein (AP-1)–binding site in the transcriptional regulatory region of LOC344967, which significantly enhanced the binding of AP-1 to the promoter region and the transcription activity of the promoter in vivo. Furthermore, the expression of LOC344967 was significantly up-regulated at both mRNA and protein levels in nasopharyngeal carcinoma cells sharing the –32G/A genotype compared with nasopharyngeal carcinoma cells with the –32G/G genotype. Collectively, these results provide evidence that the –32A variant is a functional sequence change and may be related to nasopharyngeal carcinoma susceptibility in the families studied. (Cancer Res 2006; 66(2): 693-700)

This article has been cited by other articles:

				Y. Shen, Q. Xu, Z. Han, H. Liu, and G.-B. Zhou Analysis of phenotype-genotype connection: the story of dissecting disease pathogenesis in genomic era in China, and beyond Phil Trans R Soc B, June 29, 2007; 362(1482): 1043 - 1061. [Abstract] [Full Text] [PDF]