Association of PLUNC gene polymorphisms with susceptibility to nasopharyngeal carcinoma in a Chinese population.

N asopharyngeal carcinoma (NPC) is a serious health problems in the southern Chinese population, with an incidence rate ranging from 15 to 50 per 100 000. NPC is an epithelial malignancy with a striking racial and geographic distribution differences. High incidence rates are observed in the southeast Chinese population, and similar rates have been reported in these people wherever they have migrated, including Singapore, Taiwan, and Hong Kong. These incidence rates are almost 100 fold higher than in white populations. The marked racial and geographic differences in NPC susceptibility are considered a multifactorial and polygenic event with environmental and genetic components and correlation with Epstein-Barr virus infection. 6–10 Genetic mapping of variants conferring a small disease risk can identify pathways in complex disorders. Thus, the hope of resolving the genetic aetiology of NPC and the mechanisms of racial and geographic differences in NPC susceptibility has prompted a search for genetic variants in gene candidates thought to play a role in the pathogenesis of the NPC. A genetic linkage study based on affected sibling pairs collected from different Chinese populations in southeast Asia, which located the susceptibility locus to within the 6p22 region, supported the involvement of the human leukocyte antigens (HLA) in the pathogenesis of NPC. Recently, two genomewide searches, carried out in 20 Cantonese speaking families from Guangdong province and 18 families from Hunan province in southern China, provided evidences of susceptibility loci for NPC on chromosome 4p15.1-q12 and 3p21.31– 21.2, respectively. 13 Case–control studies have established associations between specific HLA molecules and NPC in several populations including Asians, whites, and North Africans. In addition to the HLA, some non-HLA loci, including the heat shock protein 70-2 (HSP70-2), cyclin D1 (CCND1), glutathione S-transferase M1 (GSTM1), and CYP2E1 genes have also shown associations with susceptibility to NPC. Based on the fact that the disease susceptibility to NPC is determined at different functional levels, such as metabolism of carcinogenic constituents, tumour antigen presentation, cell cycle regulation, and antigenic peptide chaperones, we hypothesised that an unknown number of other unidentified genes are likely to modify the susceptibility to NPC. PLUNC (palate, lung, and nasal epithelial clone, also designated YH1, LUNX, NASG, SPURT, and SPLUNC1) is a newly identified human homologue of the murine plunc gene, and, like the mouse gene, is specifically expressed in the upper airways and nasopharyngeal regions. The abnormal expression of PLUNC may be an important molecular event in NPC development; it was found to be downregulated in 34/48 NPC biopsies. It has been reported that CNE-2Z cells transfected with PLUNC had a significant decrease in cell proliferation. More interestingly, this gene is located on chromosome segment 20q11.2, and the loss 28 or gain of chromosome arm 20q has been previously described in NPC. On the basis of the potential functional relevance of PLUNC in the pathogenesis of NPC in vivo and in vitro, we hypothesised that PLUNC might be an excellent biological candidate susceptibility gene for NPC. It is expected that genetic polymorphisms within PLUNC could result in genotype dependent differences in susceptibility to NPC. In the present study, we therefore systematically screened single nucleotide polymorphisms (SNPs) in PLUNC, and investigated association of the polymorphisms in PLUNC with susceptibility to NPC in the Chinese population. Key points