title: Genetic polymorphisms in host innate immune sensor genes and the risk of nasopharyngeal carcinoma in North Africa.
abstract: Nasopharyngeal carcinoma (NPC) is a rare malignancy in most parts of the world. It is an Epstein-Barr virus-associated malignancy with an unusual racial and geographical distribution. The host innate immune sensor genes play an important role in infection recognition and immune response against viruses. Therefore, we examined the association between polymorphisms in genes within a group of pattern recognition receptors (including families of Toll-like receptors, C-type lectin receptors, and retinoic acid-inducible gene I-like receptors) and NPC susceptibility. Twenty-six single-nucleotide polymorphisms (SNPs) in five pattern-recognition genes were genotyped in 492 North African NPC cases and 373 frequency-matched controls. TLR3_rs3775291 was the most significantly associated SNP (odds ratio [OR] 1.49; 95% confidence interval [95% CI] 1.11-2.00; P = 0.008; dominant model). The analysis showed also that CD209_rs7248637 (OR 0.69; 95% CI 0.52-0.93; P = 0.02; dominant model) and DDX58_rs56309110 (OR 0.70; 95% CI 0.51-0.98; P = 0.04) were associated with the risk of NPC. An 18% increased risk per allele was observed for the five most significantly associated SNPs, TLR3_rs3775291, CD209_rs7248637, DDX58_rs56309110, CD209_rs4804800, and MBL2_rs10824792, (ptrend = 8.2 × 10(-4)). Our results suggest that genetic variation in pattern-recognition genes is associated with the risk of NPC. These preliminary findings require replication in larger studies.
authors.affiliation: Department of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Khalid
authors.initials: K
authors.lastname: Moumad
authors.forename: Jesus
authors.initials: J
authors.lastname: Lascorz
authors.forename: Melanie
authors.initials: M
authors.lastname: Bevier
authors.forename: Meriem
authors.initials: M
authors.lastname: Khyatti
authors.forename: Moulay Mustapha
authors.initials: MM
authors.lastname: Ennaji
authors.forename: Abdellatif
authors.initials: A
authors.lastname: Benider
authors.forename: Stefanie
authors.initials: S
authors.lastname: Huhn
authors.forename: Shun
authors.initials: S
authors.lastname: Lu
authors.forename: Lotfi
authors.initials: L
authors.lastname: Chouchane
authors.forename: Marilys
authors.initials: M
authors.lastname: Corbex
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.forename: Asta
authors.initials: A
authors.lastname: Försti
mesh_terms: D000293:Adolescent; D000328:Adult; D000352:Africa, Northern; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma; D002648:Child; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease; D054884:Host-Pathogen Interactions / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
keywords: Epstein-Barr virus; North Africa; SNPs; host innate immune sensors; nasopharyngeal carcinoma