title: Genome-wide association study identifies common genetic variants associated with salivary gland carcinoma and its subtypes.
abstract: BACKGROUND
  Salivary gland carcinomas (SGCs) are a rare malignancy with unknown etiology. The objective of the current study was to identify genetic variants modifying the risk of SGC and its major subtypes: adenoid cystic carcinoma and mucoepidermoid carcinoma.
  
  
  METHODS
  The authors conducted a genome-wide association study in 309 well-defined SGC cases and 535 cancer-free controls. A single-nucleotide polymorphism (SNP)-level discovery study was performed in non-Hispanic white individuals followed by a replication study in Hispanic individuals. A logistic regression analysis was applied to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). A meta-analysis of the results was conducted.
  
  
  RESULTS
  A genome-wide significant association with SGC in non-Hispanic white individuals was detected at coding SNPs in CHRNA2 (cholinergic receptor, nicotinic, alpha 2 [neuronal]) (OR, 8.55; 95% CI, 4.53-16.13 [P = 3.6 × 10(-11)]), OR4F15 (olfactory receptor, family 4, subfamily F, member 15) (OR, 5.26; 95% CI, 3.13-8.83 [P = 3.5 × 10(-10)]), ZNF343 (zinc finger protein 343) (OR, 3.28; 95% CI, 2.12-5.07 [P = 9.1 × 10(-8)]), and PARP4 (poly(ADP-ribose) polymerase family, member 4) (OR, 2.00; 95% CI, 1.54-2.59 [P = 1.7 × 10(-7)]). Meta-analysis of the non-Hispanic white and Hispanic cohorts identified another genome-wide significant SNP in ELL2 (meta-OR, 1.86; 95% CI, 1.48-2.34 [P = 1.3 × 10(-7)]). Risk alleles were largely enriched in mucoepidermoid carcinoma, in which the SNPs in CHRNA2, OR4F15, and ZNF343 had ORs of 15.71 (95% CI, 6.59-37.47 [P = 5.2 × 10(-10)]), 15.60 (95% CI, 6.50-37.41 [P = 7.5 × 10(-10)]), and 6.49 (95% CI, 3.36-12.52 [P = 2.5 × 10(-8)]), respectively. None of these SNPs retained a significant association with adenoid cystic carcinoma.
  
  
  CONCLUSIONS
  To the best of the authors' knowledge, the current study is the first to identify a panel of SNPs associated with the risk of SGC. Confirmation of these findings along with functional analysis of identified SNPs are needed.
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Tang
authors.affiliation: Clincal Research, Quality Improvement, Baylor College of Medicine, Houston, Texas.
authors.forename: Diane W
authors.initials: DW
authors.lastname: Chen
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Adel K
authors.initials: AK
authors.lastname: El-Naggar
authors.affiliation: Division of Biostatistics and Human Genetics Center, School of Public Health, The University of Texas Health Science Center, Houston, Texas.
authors.forename: Peng
authors.initials: P
authors.lastname: Wei
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.|Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
mesh_terms: D000328:Adult; D002277:Carcinoma / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics; D018035:Receptors, Odorant / Q000235:genetics; D012468:Salivary Gland Neoplasms / Q000235:genetics*; D035602:Transcriptional Elongation Factors / Q000235:genetics; D044465:White People / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics
chemical_list: C436489:CHRNA2 protein, human; C447613:ELL2 protein, human; D009687:Nuclear Proteins; C118687:PARP4 protein, human; D011978:Receptors, Nicotinic; D018035:Receptors, Odorant; D035602:Transcriptional Elongation Factors
keywords: adenoid cystic carcinoma; genetics; genome-wide association study (GWAS); mucoepidermoid carcinoma; salivary gland
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