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) |
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Authors: | Abul Kalam Azad Xin Qiu Kevin Boyd Qin Kuang Marjan Emami Nicole Perera Prakruthi Palepu Devalben Patel Zhuo Chen Dangxiao Cheng Ronald Feld Natasha B Leighl Frances A Shepherd Ming-Sound Tsao Wei Xu Geoffrey Liu Sinead Cuffe |
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Institution: | 1. Ontario Cancer Institute, Princess Margaret Cancer Center/University Health Network, University of Toronto, Toronto, Ontario, Canada;2. Division of Medical Oncology and Hematology, Princess Margaret Cancer Center/University Health Network, University of Toronto, Toronto, Ontario, Canada;3. Department of Biostatistics, Princess Margaret Cancer Center/University Health Network, University of Toronto, Toronto, Ontario, Canada;4. Department of Pathology, Princess Margaret Cancer Center/University Health Network, University of Toronto, Toronto, Ontario, Canada;5. Division of Epidemiology, Dalla Lana School of Public Health, Toronto, Ontario, Canada |
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Abstract: | IntroductionLung 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.MethodsA 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.ResultsAfter 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).ConclusionA 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. |
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Keywords: | Genetic sequence variant Non-small cell lung cancer Survival outcomes |
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