Polymeric immunoglobulin receptor polymorphisms and risk of nasopharyngeal cancer.
BACKGROUND
Epstein-Barr virus (EBV) associated nasopharyngeal cancer (NPC) is an important squamous cell cancer endemic in Southeast Asia and the Far East and can be considered a multifactorial genetic disease. This research explores potential associations between nasopharyngeal epithelial EBV receptor and NPC susceptibility. To prove the hypothesis, we evaluated two candidate genes, complement receptor 2 (CR2) and polymeric immunoglobulin receptor (PIGR) by using 4 SNPs, CR2IVS2-848C-->T, PIGRIVS3-156G-->T, PIGR1093G-->A and PIGR1739C-->T, to genotype 175 cases and 317 controls, divided into Thai, Chinese and Thai-Chinese based on their respective ethnic origins.


RESULTS
The results obtained indicated that PIGR is an NPC susceptibility gene. The risk association pertaining to each ethnic group was detected for homozygous PIGR1739C with a significant ethnic group adjusted OR (95%CI) of 2.71(1.72-4.23) and p < 0.00001. Haplotype of the two missense PIGR SNPs, 1093G-->A and 1739C-->T, and sequence analyses have confirmed the role of the nucleotide PIGR1739 and excluded possibility of an additional significant nonsynonymous NPC susceptibility SNP.


CONCLUSIONS
We present genetic evidence leading to hypothesize a possibility of PIGR to function as the EBV nasopharyngeal epithelium receptor via IgA-EBV complex transcytosis failure. The PIGR1739C-->T is a missense mutation changing alanine to valine near endoproteolytic cleavage site. This variant could alter the efficiency of PIGR to release IgA-EBV complex and consequently increase the susceptibility of populations in endemic areas to develop NPC.
Hirunsatit
Rungnapa
R
Genetics Unit, Department of Anatomy, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Thailand. rungnapahi@yahoo.com
Kongruttanachok
Narisorn
N
Shotelersuk
Kanjana
K
Supiyaphun
Pakpoom
P
Voravud
Narin
N
Sakuntabhai
Anavaj
A
Mutirangura
Apiwat
A
D016022:Case-Control Studies; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D009303:Nasopharyngeal Neoplasms / Q000235:genetics*; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D017464:Receptors, Complement 3d / Q000235:genetics; D019056:Receptors, Polymeric Immunoglobulin / Q000235:genetics*
D017464:Receptors, Complement 3d; D019056:Receptors, Polymeric Immunoglobulin; D004247:DNA