title: Systematic Review of Genetic Variation in Chromosome 5p15.33 and Telomere Length as Predictive and Prognostic Biomarkers for Lung Cancer.
abstract: Lung cancer remains the leading cause of cancer mortality worldwide. Known histomolecular characteristics and genomic profiles provide limited insight into factors influencing patient outcomes. Telomere length (TL) is important for genomic integrity and has been a growing area of interest as agents targeting telomerase are being evaluated. Chromosome 5p15.33, an established cancer susceptibility locus, contains a telomerase-regulatory gene, TERT, and CLPTM1L, a gene associated with cisplatin-induced apoptosis. This review offers a summary of the clinical utility of 5p15.33 polymorphisms and TL. A total of 621 abstracts were screened, and 14 studies (7 for 5p15.33, 7 for TL) were reviewed. Endpoints included overall survival (OS), progression-free survival (PFS), therapy response, and toxicity. Of the 23 genetic variants identified, significant associations with OS and/or PFS were reported for rs401681 (CLPTM1L), rs4975616 (TERT-CLPTM1L), and rs2736109 (TERT). Both shorter and longer TL, in tumor and blood, was linked to OS and PFS. Overall, consistent evidence across multiple studies of 5p15.33 polymorphisms and TL was lacking. Despite the potential to become useful prognostic biomarkers in lung cancer, the limited number of reports and their methodologic limitations highlight the need for larger, carefully designed studies with clinically defined subpopulations and higher resolution genetic analyses. Cancer Epidemiol Biomarkers Prev; 25(12); 1537-49. ©2016 AACR.
authors: Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.|Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.|Prevention & Cancer Control, Cancer Care Ontario, Toronto, Ontario, Canada.
authors: Linda
authors: L
authors: Kachuri
authors: Prevention & Cancer Control, Cancer Care Ontario, Toronto, Ontario, Canada.
authors: Lidija
authors: L
authors: Latifovic
authors: Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.|Ontario Cancer Institute, Princess Margaret Cancer Center, Toronto, Ontario, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors: Geoffrey
authors: G
authors: Liu
authors: Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada. rayjean.hung@lunenfeld.ca.|Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
authors: Rayjean J
authors: RJ
authors: Hung
mesh_terms: D002895:Chromosomes, Human, Pair 5; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D019098:Telomerase / Q000235:genetics; D059505:Telomere Homeostasis
chemical_list: C422445:CLPTM1L protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C509186:TERT protein, human; D019098:Telomerase