A functional variant in the transcriptional regulatory region of gene LOC344967 cosegregates with disease phenotype in familial nasopharyngeal carcinoma.

Abstract

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.

• Authors: Ri-Cheng Jiang, Hai-De Qin, Mu-Sheng Zeng, Wei Huang, Bing-Jian Feng, Feng Zhang, Han-Kui Chen, Wei-Hua Jia, Li-Zhen Chen, Qi-Sheng Feng, Ru-Hua Zhang, Xing-Juan Yu, Mei-Zhen Zheng, Yi-Xin Zeng
• Journal: Cancer research (Cancer Res) Vol. 66 Issue 2 Pg. 693-700 (Jan 15 2006) ISSN: 0008-5472 [Print] United States
• PMID: 16423998 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• LOC344967 protein, human
• Transcription Factors

Topics

• Carcinoma (genetics, pathology)
• Exons
• Genetic Predisposition to Disease
• Humans
• Nasopharyngeal Neoplasms (genetics, pathology)
• Pedigree
• Phenotype
• Polymorphism, Single Nucleotide
• Promoter Regions, Genetic
• Transcription Factors (genetics, physiology)
• Transcription, Genetic