Genome-wide association study identifies common genetic variants associated with salivary gland carcinoma and its subtypes

Cancer. 2015 Jul 15;121(14):2367-74. doi: 10.1002/cncr.29381. Epub 2015 Mar 30.

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.

Keywords: adenoid cystic carcinoma; genetics; genome-wide association study (GWAS); mucoepidermoid carcinoma; salivary gland.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Adult
  • Carcinoma / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Nuclear Proteins / genetics
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Receptors, Nicotinic / genetics
  • Receptors, Odorant / genetics
  • Salivary Gland Neoplasms / genetics*
  • Transcriptional Elongation Factors / genetics
  • White People / genetics*
  • Zinc Fingers / genetics

Substances

  • CHRNA2 protein, human
  • ELL2 protein, human
  • Nuclear Proteins
  • PARP4 protein, human
  • Receptors, Nicotinic
  • Receptors, Odorant
  • Transcriptional Elongation Factors