Genome-wide association study identifies common genetic variants associated with salivary gland carcinoma and its subtypes.
Genome-wide association study identifies common genetic variants associated with salivary gland carcinoma and its subtypes.
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DOI：
10.1002/cncr.29381
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发表时间：
2015-07-15
期刊：
影响因子：
6.2
通讯作者：
Sturgis EM
中科院分区：
文献类型：
--
作者：
Xu L;Tang H;Chen DW;El-Naggar AK;Wei P;Sturgis EM
涎腺癌是一种罕见的恶性肿瘤，其病因不明。我们的目的是确定遗传变异修改的风险SGC及其主要亚型，腺样囊性癌（ACCA）和粘液表皮样癌（MECA）。我们在309例明确的SGC病例和535例无癌对照中进行了全基因组关联研究。我们在非西班牙裔白人中进行了SNP水平的发现研究，然后在西班牙裔中进行了复制研究。应用逻辑回归计算比值比（OR）和95%置信区间（95%CI）。对结果进行荟萃分析。在CHRNA 2中的编码SNPs检测到非西班牙裔白人中与SGC的全基因组显著关联（OR=8.55，95%CI：4.53-16.13，P = 3.6 × 10−11），OR4F15（OR=5.26，95%CI：3.13-8.83，P = 3.5 × 10−10）、ZNF 343（OR=3.28，95%CI：2.12-5.07，P = 9.1 × 10−8）和PARP4（OR=2.00，95%CI：1.54-2.59，P = 1.7 × 10−7）。非西班牙裔白色和西班牙裔队列的荟萃分析确定了ELL 2中另一个全基因组显著SNP（荟萃OR =1.86，95%CI：1.48-2.34，P = 1.3 × 10−7）。风险等位基因在MECA中大量富集，其中CHRNA 2、OR 4F 15和ZNF 343中的SNP的OR为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）和6.49（95%CI：3.36-12.52，P = 2.5 × 10−8）。这些SNPs均未与ACCA保持显著关联。这些发现首次确定了一组与SGC风险相关的SNP。需要沿着对这些发现的确认以及对已鉴定的SNP的功能分析。
Salivary gland carcinomas (SGCs) are a rare malignancy with unknown etiology. We aimed to identify genetic variants modifying risk of SGC and its major subtypes, adenoid cystic carcinoma (ACCA) and mucoepidermoid carcinoma (MECA). We conducted a genome-wide association study in 309 well-defined SGC cases and 535 cancer-free controls. We performed a SNP-level discovery study in non-Hispanic whites followed by a replication study in Hispanics. A logistic regression was applied to calculate odds ratios (ORs) and 95% confidence intervals (95%CIs). A meta-analysis was conducted of the results. Genome-wide significant association with SGC in non-Hispanic whites was detected at coding SNPs in CHRNA2 (OR=8.55, 95%CI: 4.53–16.13, P = 3.6 × 10−11), OR4F15 (OR=5.26, 95%CI: 3.13–8.83, P = 3.5 × 10−10), ZNF343 (OR=3.28, 95%CI: 2.12–5.07, P = 9.1 × 10−8), and PARP4 (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 largely enriched in MECA, where 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 significant association with ACCA. These findings, for the first time, identify a panel of SNPs associated with SGC risk. Confirmation of these findings along with functional analysis of identified SNPs are needed.