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.
Highlights
Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death worldwide (1)
Few publications were selected for full review because the majority of the articles were focused on functional characterizations of the 5p15.33 locus, TERT/ CLPTM1L expression, or telomerase activity
Advances in molecular biology and epidemiology can identify accurate and reliable biomarkers and improve stratification of the patients into more precise groups to assist in selection of optimal treatment modalities, as have been seen in the case of EGFR mutations and anaplastic lymphoma kinase (ALK) rearrangements
Summary
Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death worldwide (1). Despite recent advances in its treatment, the general prognosis for lung cancer remains poor, with low 5-year survival rates of under 15% (2). Our current understanding of the factors influencing interindividual variability in outcomes is limited, as clinic–demographic factors (age, sex, smoking, and disease stage) and histomolecular factors, including tumor histology, somatic molecular changes, such as EGFR mutations or anaplastic lymphoma kinase (ALK) rearrangements, only provide a partial picture (3). This underscores the need to identify noninvasive, Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/).
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