Polymeric immunoglobulin receptor polymorphisms and risk of nasopharyngeal cancer

BMC Genet. 2003 Jan 21;4:3. doi: 10.1186/1471-2156-4-3. Epub 2003 Jan 21.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • DNA / chemistry
  • DNA / genetics
  • DNA Mutational Analysis
  • Female
  • Gene Frequency
  • Genotype
  • Haplotypes
  • Humans
  • Male
  • Mutation, Missense
  • Nasopharyngeal Neoplasms / genetics*
  • Odds Ratio
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide*
  • Receptors, Complement 3d / genetics
  • Receptors, Polymeric Immunoglobulin / genetics*

Substances

  • Receptors, Complement 3d
  • Receptors, Polymeric Immunoglobulin
  • DNA