Author(s): Xu L, Tang H, Chen DW, El-Naggar AK, Wei P, et al.
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.
METHODSThe 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.
RESULTSA 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.
CONCLUSIONSTo 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.
Referred From: https://doi.org/10.1002/cncr.29381
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