Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
Genomics Research Center, Academia Sinica, Taipei, Taiwan.
Cancer Epidemiol Biomarkers Prev. 2019 Oct;28(10):1682-1686. doi: 10.1158/1055-9965.EPI-19-0007. Epub 2019 Jul 3.
Genetic susceptibility is associated with nasopharyngeal carcinoma (NPC). We previously identified rare variants potentially involved in familial NPC and common variants significantly associated with sporadic NPC.
We conducted targeted gene sequencing of 20 genes [16 identified from the study of multiplex families, three identified from a pooled analysis of NPC genome-wide association study (GWAS), and one identified from both studies] among 819 NPC cases and 938 controls from two case-control studies in Taiwan (independent from previous studies). A targeted, multiplex PCR primer panel was designed using the custom Ion AmpliSeq Designer v4.2 targeting the regions of the selected genes. Gene-based and single-variant tests were conducted.
We found that NPC was associated with combined common and rare variants in ( = 1.3 × 10), ( = 1.6 × 10), ( = 4.0 × 10), and ( = 5.4 × 10). Such associations were likely driven by common variants within these genes, based on gene-based analyses evaluating common variants and rare variants separately (e.g., for common variants of = 4.6 × 10; for rare variants, = 0.04). We also observed a suggestive association with rare variants in ( = 3.8 × 10) for NPC risk. In addition, we validated four previously reported NPC risk-associated SNPs.
Our findings confirm previously reported associated variants and suggest that some common variants in genes previously linked to familial NPC are associated with the development of sporadic NPC.
NPC-associated genes, including , and , suggest a role for telomere length maintenance in NPC etiology.
遗传易感性与鼻咽癌（NPC）有关。我们之前已经确定了一些可能与家族性 NPC 有关的罕见变异，以及与散发性 NPC 显著相关的常见变异。
我们对来自台湾两个病例对照研究（与之前的研究独立）的 819 例 NPC 病例和 938 例对照进行了 20 个基因的靶向基因测序（16 个基因是从多基因家族研究中确定的，3 个基因是从 NPC 全基因组关联研究的合并分析中确定的，1 个基因是从两个研究中确定的）。使用定制的 Ion AmpliSeq Designer v4.2 设计靶向选择基因区域的靶向、多重 PCR 引物组。进行了基于基因和单变体的测试。
我们发现 NPC 与 （ = 1.3 × 10）、 （ = 1.6 × 10）、 （ = 4.0 × 10）和 （ = 5.4 × 10）中的常见和罕见变异均有关联。基于分别评估常见变异和罕见变异的基因分析，这些关联可能是由这些基因中的常见变异驱动的（例如，对于常见变异， = 4.6 × 10；对于罕见变异， = 0.04）。我们还观察到 （ = 3.8 × 10）与 NPC 风险的罕见变异有提示性关联。此外，我们还验证了四个先前报道的 NPC 风险相关的 SNP。
我们的研究结果证实了先前报道的相关变异，并表明一些先前与家族性 NPC 相关的基因中的常见变异与散发性 NPC 的发生有关。
与 NPC 相关的基因，包括 、 和 ，表明端粒长度维持在 NPC 发病机制中起作用。
