Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Investigation of Leukocyte Telomere Length and Genetic Variants in Chromosome 5p15.33 as Prognostic Markers in Lung Cancer

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Risk of Anal Cancer Following Benign Anal Disease and Anal Cancer Precursor Lesions: A Danish Nationwide Cohort Study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. A Cohort Study of Breast Cancer Risk after 20 Years of Follow-Up of Women Treated with Fertility Drugs

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Elevated platelet count appears to be causally associated with increased risk of lung cancer: A Mendelian randomization analysis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Transcriptome-wide association study reveals candidate causal genes for lung cancer

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Reply to: Clinical impact of high platelet count and high hematocrit, by Marc Sorigue

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. A network analysis to identify mediators of germline-driven differences in breast cancer prognosis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Incidental lymphopenia and mortality: a prospective cohort study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Immune-mediated genetic pathways resulting in pulmonary function impairment increase lung cancer susceptibility

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Linda Kachuri
  • Jens Helby
  • Stig Egil Bojesen
  • David C Christiani
  • Li Su
  • Xifeng Wu
  • Adonina Tardón
  • Guillermo Fernández-Tardón
  • John K Field
  • Michael P Davies
  • Chu Chen
  • Gary E Goodman
  • Frances A Shepherd
  • Natasha B Leighl
  • Ming S Tsao
  • Yonathan Brhane
  • M Catherine Brown
  • Kevin Boyd
  • Daniel Shepshelovich
  • Lei Sun
  • Christopher I Amos
  • Geoffrey Liu
  • Rayjean J Hung
Vis graf over relationer

BACKGROUND: Lung cancer remains the leading cause of cancer mortality with relatively few prognostic biomarkers. We investigated associations with overall survival for telomere length (TL) and genetic variation in chromosome 5p15.33, an established telomere maintenance locus.

METHODS: Leukocyte TL was measured after diagnosis in 807 patients with non-small cell lung cancer (NSCLC) from the Princess Margaret Cancer Center in Toronto and assessed prospectively in 767 NSCLC cases from the Copenhagen City Heart Study and the Copenhagen General Population Study. Associations with all-cause mortality were tested for 723 variants in 5p15.33, genotyped in 4,672 NSCLC cases.

RESULTS: Short telomeres (≤10th percentile) were associated with poor prognosis for adenocarcinoma in both populations: TL measured 6 months after diagnosis [HR = 1.65; 95% confidence intervals (CI), 1.04-2.64] and for those diagnosed within 5 years after blood sampling (HR = 2.42; 95% CI, 1.37-4.28). Short TL was associated with mortality in never smokers with NSCLC (HR = 10.29; 95% CI, 1.86-56.86) and adenocarcinoma (HR = 11.31; 95% CI, 1.96-65.24). Analyses in 5p15.33 identified statistically significant prognostic associations for rs56266421-G in LPCAT1 (HR = 1.86; 95% CI, 1.38-2.52; P = 4.5 × 10-5) in stage I-IIIA NSCLC, and for the SLC6A3 gene with OS in females with NSCLC (P = 1.6 × 10-3).

CONCLUSIONS: Our findings support the potential clinical utility of TL, particularly for adenocarcinoma patients, while associations in chromosome 5p15.33 warrant further exploration.

IMPACT: This is the largest lung cancer study of leukocyte TL and OS, and the first to examine the impact of the timing of TL measurement. Our findings suggest that extremely short telomeres are indicative of poor prognosis in NSCLC.

OriginalsprogEngelsk
TidsskriftCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Vol/bind28
Udgave nummer7
Sider (fra-til)1228-1237
Antal sider10
ISSN1055-9965
DOI
StatusUdgivet - jul. 2019

Bibliografisk note

©2019 American Association for Cancer Research.

ID: 59350214