Department of Life Science, Sogang University, Seoul, Republic of Korea.
Department of Genetic Epidemiology, SNP Genetics Inc., Seoul, Republic of Korea.
PLoS One. 2018 Nov 21;13(11):e0207660. doi: 10.1371/journal.pone.0207660. eCollection 2018.
Previous studies have identified multiple loci for inherited susceptibility to glioma development, including the regulator of telomere elongation helicase 1 (RTEL1). However, the association between RTEL1 variants and risk of glioma has not been well understood. Therefore, we sought to comprehensively examine the genetic interaction between RTEL1 variants and risk of glioma with respect to defined histological and molecular subtypes. We employed a case-control study involving 250 adult glioma patients with previous molecular alterations and 375 population-based controls within Korean populations. Statistical analyses on the association between RTEL1 single nucleotide polymorphisms (SNPs) and glioma risk were conducted using unconditional logistic regression. Additional conditional and stepwise analyses were performed on significant RTEL1 SNPs. We detected significant associations (Bonferroni P < .05) between six SNPs (rs6089953, rs3848669, rs6010620, rs3787089, rs6062302, and rs115303435) and risk of glioma in the Korean subjects. The two coding variants, rs6062302 (D664D) and rs115303435 (A1059T), were plausibly causal variants and were independent among the significantly associated RTEL1 variants. The glioma subgroup analyses showed that the causal variants (rs6062302 and rs115303435) may be associated with increased risk of glioma regardless of histological grades and molecular alterations. This study provides a deeper understanding of relationships between RTEL1 variants and risk of glioma. Further studies are required to ascertain the impact of those variants on glioma susceptibility.
先前的研究已经确定了多个与胶质瘤发生的遗传易感性相关的基因座，包括端粒延长螺旋酶 1（RTEL1）。然而，RTEL1 变体与胶质瘤风险之间的关联尚未得到很好的理解。因此，我们试图全面研究 RTEL1 变体与特定组织学和分子亚型的胶质瘤风险之间的遗传相互作用。我们采用病例对照研究，纳入了 250 名韩国成年人胶质瘤患者，这些患者以前有分子改变，以及 375 名基于人群的对照者。使用无条件逻辑回归对 RTEL1 单核苷酸多态性（SNP）与胶质瘤风险之间的关联进行了统计分析。对有意义的 RTEL1 SNP 进行了附加的条件和逐步分析。我们在韩国人群中检测到六个 SNP（rs6089953、rs3848669、rs6010620、rs3787089、rs6062302 和 rs115303435）与胶质瘤风险之间存在显著关联（Bonferroni P <.05）。这两个编码变体，rs6062302（D664D）和 rs115303435（A1059T）是合理的因果变体，并且在与 RTEL1 显著相关的变体中是独立的。胶质瘤亚组分析表明，这些因果变体（rs6062302 和 rs115303435）可能与无论组织学分级和分子改变如何，胶质瘤风险增加相关。本研究加深了对 RTEL1 变体与胶质瘤风险之间关系的理解。需要进一步的研究来确定这些变体对胶质瘤易感性的影响。
