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Objective: Epstein-Barr virus (EBV) associated nasopharyngeal carcinoma (NPC) is an important squamous cell cancer endemic in south China and Southeast Asia. pIgR (polymeric immunoglobulin receptor) gene plays central roles during immune responses and EBV inflammatory and therefore is a good candidate susceptibility gene for NPC. This study is to evaluated potential associations between pIgR gene and NPC susceptibility. Methods: Sequencing was used to identify multiple single nucleotide polymorphisms (SNPs) within the exon regions of pIgR in Guangdong population. Four SNPs were genotyped in 528 NPC patients and 408 normal individuals to perform case-control study. Results: There was no statistical difference in the allele frequencies of each SNP (P>0.05). After categorized into 2 groups by age of 45 y, in the group of age below 45 the minor allele T frequency of C888oT was 7%, whereas 4% in controls, with significant difference (P<0.05). The Odds Ratio (OR=1.84) also showed higher risk of NPC with individuals carried the minor alleles. Conclusion: The result has proved that SNP C8880T is associated with NPC susceptibility and pIgR gene might play a certain role in oncogenesis and development of NPC.