在局部晚期和转移性非小细胞肺癌（NSCLC）中，位于 5p15.33（TERT-CLPTM1L）易感位点的遗传序列变异（GSV）与生存结局相关。
A genetic sequence variant (GSV) at susceptibility loci of 5p15.33 (TERT-CLPTM1L) is associated with survival outcome in locally advanced and metastatic non-small-cell lung cancer (NSCLC).
机构信息
Ontario Cancer Institute, Princess Margaret Cancer Center/University Health Network, University of Toronto, Toronto, Ontario, Canada.
Department of Biostatistics, Princess Margaret Cancer Center/University Health Network, University of Toronto, Toronto, Ontario, Canada.
出版信息
Lung Cancer. 2014 Jun;84(3):289-94. doi: 10.1016/j.lungcan.2014.03.008. Epub 2014 Mar 13.
INTRODUCTION
Lung cancer is a leading cause of cancer-related mortality in North America. In addition to tobacco smoking, inherited genetic factors can also influence the development of lung cancer. These genetic factors may lead to biologically distinct subsets of cancers that have different outcomes. We evaluated whether genetic sequence variants (GSVs) associated with lung cancer risk are associated with overall survival (OS) and progression-free survival (PFS) in stage-III-IV non-small-cell lung cancer (NSCLC) patients.
METHODS
A total of 20 candidate GSVs in 12 genes previously reported to be associated with lung cancer risk were genotyped in 564 patients with stage-III or IV NSCLC. Multivariate Cox proportional hazard models adjusted for potential clinical prognostic factors were generated for OS and PFS.
RESULTS
After taking into account multiple comparisons, one GSV remained significant: rs4975616 on chromosome 5p15.33, located near the TERT-CLPTM1L gene. The adjusted hazard ratio (aHR) for OS was 0.75 (0.69-0.91), p = 0.002; for PFS aHR was 0.74 (0.62-0.89), p < 0.001 for each protective variant allele. Results were similar in both Stage III (OS: aHR = 0.70; PFS: aHR = 0.71) and Stage IV patients (OS: aHR = 0.81; PFS: aHR = 0.77).
CONCLUSION
A GSV on 5p15.33 is not only a risk factor for lung cancer but may also be associated with survival in patients with late stage NSCLC. If validated, GSVs may define subsets of patients with different risk and prognosis of NSCLC.
简介
肺癌是北美癌症相关死亡的主要原因。除了吸烟外，遗传基因因素也会影响肺癌的发展。这些遗传因素可能导致癌症具有不同的生物学亚群，从而导致不同的结局。我们评估了与肺癌风险相关的遗传序列变异（GSV）是否与 III 期-IV 期非小细胞肺癌（NSCLC）患者的总生存期（OS）和无进展生存期（PFS）相关。
方法
在 564 名 III 期或 IV 期 NSCLC 患者中，对先前报道与肺癌风险相关的 12 个基因中的 20 个候选 GSV 进行了基因分型。针对 OS 和 PFS，生成了调整潜在临床预后因素的多变量 Cox 比例风险模型。
结果
在考虑了多次比较后，一个 GSV 仍然具有统计学意义：位于 5p15.33 染色体上的 rs4975616，位于 TERT-CLPTM1L 基因附近。OS 的调整后的危险比（aHR）为 0.75（0.69-0.91），p = 0.002；对于 PFS，aHR 为 0.74（0.62-0.89），对于每个保护性变异等位基因，p < 0.001。在 III 期（OS：aHR = 0.70；PFS：aHR = 0.71）和 IV 期患者（OS：aHR = 0.81；PFS：aHR = 0.77）中，结果相似。
结论
5p15.33 上的 GSV 不仅是肺癌的危险因素，而且可能与晚期 NSCLC 患者的生存相关。如果得到验证，GSV 可能会定义 NSCLC 患者不同风险和预后的亚群。
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