[Show abstract][Hide abstract] ABSTRACT: As members of adhesion molecule families, CD44 transmembrane glycoproteins have been originally thought to be essential for the formation of multicellular organisms and soon recognised to be able to initiate metastatic spread of tumour cells. To investigate the association between CD44 polymorphisms and nasopharyngeal carcinoma (NPC), we carried out a two-stage case-control study in 906 patients and 943 healthy controls in Eastern populations. Five single nucleotide polymorphisms of CD44 (rs10836347C>T, rs13347C>T, rs1425802A>G, rs11821102G>A and rs713330T>C) with proper frequency were selected from the HapMap database and genotyped with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Compared with the most common rs13347CC genotype, CT+TT genotypes significantly increased individuals' susceptibility to NPC (odds ratio = 2.58, 95% confidence interval = 2.13-3.13). Furthermore, our transient transfection focusing on reporter gene expression modulated by CD44 3'UTR demonstrated that the presence of an rs13347T allele led to greater transcriptional activity than the C allele. Similarly, more CD44 expression was shown in rs13347T carriers than C carriers in our western blotting results. All these findings suggest that CD44 rs13347C>T polymorphism may affect NPC development by improving CD44 expression.
[Show abstract][Hide abstract] ABSTRACT: The tumor suppressor TP53 and its negative regulator MDM2 play crucial roles in carcinogenesis. Previous case-control studies also revealed TP53 72Arg>Pro and MDM2 309T>G polymorphisms contribute to the risk of common cancers. However, the relationship between these two functional polymorphisms and nasopharyngeal carcinoma (NPC) susceptibility has not been explored.
In this study, we performed a case-control study between 522 NPC patients and 722 healthy controls in a Chinese population by using PCR-RFLP.
We found an increased NPC risk associated with the MDM2 GG (odds ratio [OR] = 2.83, 95% confidence interval [CI] = 2.08-3.96) and TG (OR = 1.49, 95% CI = 1.16-2.06) genotypes. An increased risk was also associated with the TP53 Pro/Pro genotype (OR = 2.22, 95% CI = 1.58-3.10) compared to the Arg/Arg genotype. The gene-gene interaction of MDM2 and TP53 polymorphisms increased adult NPC risk in a more than multiplicative manner (OR for the presence of both MDM2 GG and TP53 Pro/Pro genotypes = 7.75, 95% CI = 3.53-17.58).
The findings suggest that polymorphisms of MDM2 and TP53 genes may be genetic modifier for developing NPC.