TY - JOUR
T1 - Leukocyte telomere length is associated with aggressive prostate cancer in localized prostate cancer patients
AU - Xu, Junfeng
AU - Chang, Wen Shin
AU - Tsai, Chia Wen
AU - Bau, Da-Tian
AU - Xu, Yifan
AU - Davis, John W.
AU - Thompson, Timothy C.
AU - Logothetis, Christopher J.
AU - Gu, Jian
N1 - Funding Information:
This study was financially supported by an individual researcher award ( RP140556 ) from the Cancer Prevention and Research Institute of Texas (CPRIT), a National Cancer Institute Specialized Program of Research Excellence (SPORE) grant ( CA140388 ), and an MD Anderson Cancer Center start-up fund. The funders had no role in study design, data collection, data analysis, interpretation, and writing of the manuscript.
Publisher Copyright:
© 2019 The Author(s)
PY - 2020/2
Y1 - 2020/2
N2 - 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.
AB - 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.
KW - Biochemical recurrence
KW - Genetic risk score
KW - Leukocyte telomere length
KW - Mendelian randomization
KW - Prostate cancer
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U2 - 10.1016/j.ebiom.2019.102616
DO - 10.1016/j.ebiom.2019.102616
M3 - Article
C2 - 31981976
AN - SCOPUS:85078156790
SN - 2352-3964
VL - 52
JO - EBioMedicine
JF - EBioMedicine
M1 - 102616
ER -