title: 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).
abstract: BACKGROUND
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Ontario Cancer Institute, Princess Margaret Cancer Center/University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Abul Kalam
authors.initials: AK
authors.lastname: Azad
authors.affiliation: Department of Biostatistics, Princess Margaret Cancer Center/University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Xin
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Ontario Cancer Institute, Princess Margaret Cancer Center/University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Kevin
authors.initials: K
authors.lastname: Boyd
authors.affiliation: Ontario Cancer Institute, Princess Margaret Cancer Center/University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Qin
authors.initials: Q
authors.lastname: Kuang
authors.affiliation: Ontario Cancer Institute, Princess Margaret Cancer Center/University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Marjan
authors.initials: M
authors.lastname: Emami
authors.affiliation: Ontario Cancer Institute, Princess Margaret Cancer Center/University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Nicole
authors.initials: N
authors.lastname: Perera
authors.affiliation: Ontario Cancer Institute, Princess Margaret Cancer Center/University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Prakruthi
authors.initials: P
authors.lastname: Palepu
authors.affiliation: Ontario Cancer Institute, Princess Margaret Cancer Center/University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Devalben
authors.initials: D
authors.lastname: Patel
authors.affiliation: Ontario Cancer Institute, Princess Margaret Cancer Center/University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Ontario Cancer Institute, Princess Margaret Cancer Center/University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Dangxiao
authors.initials: D
authors.lastname: Cheng
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Center/University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ronald
authors.initials: R
authors.lastname: Feld
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Center/University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Natasha B
authors.initials: NB
authors.lastname: Leighl
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Center/University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Frances A
authors.initials: FA
authors.lastname: Shepherd
authors.affiliation: Department of Pathology, Princess Margaret Cancer Center/University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ming-Sound
authors.initials: MS
authors.lastname: Tsao
authors.affiliation: Department of Biostatistics, Princess Margaret Cancer Center/University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Ontario Cancer Institute, Princess Margaret Cancer Center/University Health Network, University of Toronto, Toronto, Ontario, Canada; Division of Medical Oncology and Hematology, Princess Margaret Cancer Center/University Health Network, University of Toronto, Toronto, Ontario, Canada; Division of Epidemiology, Dalla Lana School of Public Health, Toronto, Ontario, Canada. Electronic address: geoffrey.liu@uhn.on.ca.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Liu
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Center/University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sinead
authors.initials: S
authors.lastname: Cuffe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D019098:Telomerase / Q000235:genetics
chemical_list: C422445:CLPTM1L protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C509186:TERT protein, human; D019098:Telomerase
keywords: Genetic sequence variant; Non-small cell lung cancer; Survival outcomes