Interesting new study from MD Anderson, below [1].
Leukocytes are white blood cells - important players in the immune response.
Telomeres are protective caps at the ends of chromosomes. They are mostly comprised of repeating sequences. When cells divide, there is a loss of one or more of the sequences. When the telomere becomes short enough, further division is not possible. This is the body's way of protecting against rapidly dividing cells - such as cancer cells. See Hayflick limit [2].
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"Our results showed for the first time that {leukocyte telomere length} was shorter in PCa patients with high Gleason scores and that short {leukocyte telomere length} and genetically predicted short {leukocyte telomere length} are associated with worse prognosis in PCa patients receiving prostatectomy or radiotherapy.
-Patrick
[1] Full Text:
thelancet.com/journals/ebio...
Abstract: ncbi.nlm.nih.gov/pubmed/319...
EBioMedicine. 2020 Jan 22;52:102616. doi: 10.1016/j.ebiom.2019.102616. [Epub ahead of print]
Leukocyte telomere length is associated with aggressive prostate cancer in localized prostate cancer patients.
Xu J1, Chang WS2, Tsai CW2, Bau DT3, Xu Y1, Davis JW4, Thompson TC5, Logothetis CJ5, Gu J6.
Author information
1
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
2
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States; Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan.
3
Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan.
4
Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
5
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
6
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States. Electronic address: jiangu@mdanderson.org.
Abstract
BACKGROUND:
Telomeres play important roles in cancer initiation and progression. The aim of this study is to investigate whether leukocyte telomere length (LTL) is associated with aggressive prostate cancer (PCa).
METHODS:
We measured relative LTL in a cohort of 1,889 white PCa patients who were treated and followed up at the University of Texas MD Anderson Cancer Center and assessed its associations with aggressive disease characteristics at diagnosis and biochemical recurrence (BCR) after active treatments (radical prostatectomy and radiotherapy). We further used a Mendelian randomization (MR) approach to compute a weighted genetic risk score (GRS) predictive of LTL using 10 established LTL-associated genetic variants and determined whether this GRS is associated with aggressive PCa.
FINDINGS:
LTL was significantly shorter in patients with higher Gleason scores at diagnosis. Dichotomized at the median value of LTL, patients with short LTL exhibited a 2.74-fold (95% confidence interval, 1.79-4.18, P = 3.11 × 10-6) increased risk of presenting with GS≥8 disease than those with long LTL in multivariate logistic regression analysis. Moreover, shorter LTL was significantly associated with an increased risk of BCR (hazard ratio = 1.53, 95% confidence interval, 1.01-2.34) compared to longer LTL in localized patients receiving prostatectomy or radiotherapy with a significant dose-response association (P for trend = 0.017) in multivariate Cox proportional hazards regression analysis. In MR analysis, genetically predicted short LTL was also associated with an increased risk of BCR (HR=1.73, 95% CI, 1.08-2.78).
INTERPRETATION:
Our results showed for the first time that LTL was shorter in PCa patients with high Gleason scores and that short LTL and genetically predicted short LTL are associated with worse prognosis in PCa patients receiving prostatectomy or radiotherapy.
FUNDING:
Cancer Prevention and Research Institute of Texas (CPRIT) grant (RP140556), National Cancer Institute Specialized Program of Research Excellence (SPORE) grant (CA140388), and MD Anderson Cancer Center start-up fund.
Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.
KEYWORDS:
Biochemical recurrence; Genetic risk score; Leukocyte telomere length; Mendelian randomization; Prostate cancer
PMID: 31981976 DOI: 10.1016/j.ebiom.2019.102616
