A rare polymorphism of the COX7B2 gene in a Cantonese family with nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is the most common head and neck cancer in southern China, and the genetic susceptibility is believed to play an important role in the aetiol-ogy of this malignancy. In our previous studies, one candidate susceptibility locus has been mapped to chromosome 4p11-p14 in a subset of NPC families. In the present study, we screened the cytochrome oxidase VIIb2 (COX7B2) gene which resides in this region and investigated the relationship of single nucleotide polymorphisms (SNPs) of this gene with these familial NPC pa-tients. We identified five novel SNPs in this gene, among them -158101G>T and -157322G>A in promoter region, -109602A>G in intron 2, 78T>A in exon 3, and 354T>A in 3?untranslational region. The change 78T>A at codon 26 which leads to CAT26CAA (His26Gln) was shared by patients from family 31 that carried the susceptibility haplotype, but not found in cases from other NPC families nor in sporadic cases. However, the frequency of allele A was relatively low in normal controls both from Guangdong and eastern China (0.45% and 0.26%, respectively), and this variant was not found in pooled DNA samples from the white and the black population. Pro-tein sequence alignment showed that the 26His of COX7B2 protein is consistent among different species. Our results suggested that the codon 26 of COX7B2 gene might be conservative during the process of evolution, and the rare variation His26Gln was probably associated with the high risk in NPC pedigree 31.