Dataset Information

Shorter Treatment-Naive Leukocyte Telomere Length is Associated with Poorer Overall Survival of Patients with Pancreatic Ductal Adenocarcinoma.

ABSTRACT:

Background

Critically shortened telomeres contribute to chromosomal instability and neoplastic transformation and are associated with early death of patients with certain cancer types. Shorter leukocyte telomere length (LTL) has been associated with higher risk for pancreatic ductal adenocarcinoma (PDAC) and might be associated also with survival of patients with PDAC. We investigated the association between treatment-naïve LTL and overall survival of patients with incident PDAC.

Methods

The study included 642 consecutively enrolled PDAC patients in the Mayo Clinic Biospecimen Resource for Pancreas Research. Blood samples were obtained at the time of diagnosis, before the start of cancer treatment, from which LTL was assayed by qRT-PCR. LTL was first modeled as a continuous variable (per-interquartile range decrease in LTL) and then as a categorized variable (short, medium, long). Multivariable-adjusted HRs and 95% confidence intervals (CI) were calculated for overall mortality using Cox proportional hazard models.

Results

Shorter treatment-naïve LTL was associated with higher mortality among patients with PDAC (HR_continuous = 1.13, 95% CI: 1.01-1.28, P = 0.03; HR_shortest _vs. _{longest LTL} = 1.29, 95% CI: 1.05-1.59, P _trend = 0.01). There was a difference in the association between LTL and overall mortality by tumor stage at diagnosis; resectable tumors (HR_continuous = 0.91; 95% CI: 0.73-1.12), locally advanced tumors (HR_continuous = 1.29; 95% CI: 1.07-1.56), and metastatic tumors (HR_continuous = 1.17; 95% CI: 0.96-1.42), P _interaction = 0.04.

Conclusion

Shorter treatment-naïve LTL is associated with poorer overall survival of patients with incident PDAC.

Impact

Peripheral blood LTL might be a prognostic marker for PDAC.

SUBMITTER: Antwi SO

PROVIDER: S-EPMC7855627 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundRecent large-scale prospective studies suggest that long telomeres are associated with an increase cancer risk, counter to conventional wisdom.MethodsTo further clarify the association between leukocyte telomere length (LTL) and prostate cancer, and assess genetic variability in relation to both LTL and prostate cancer, we performed a nested case-control study (922 cases and 935 controls). The participants provided blood in 1993-1995 and were followed through August 2004 (prostate cancer incidence) or until 28 February 2013 (lethal or fatal prostate cancer). Relative LTL was measured by quantitative PCR and was calculated as the ratio of telomere repeat copy number to a single gene (36B4) copy number (T/S). Genotyping was performed using the TaqMan OpenArray SNP Genotyping Platform. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of all prostate cancer and subtypes defined by Gleason grade, stage and lethality (metastasis or death).ResultsWe observed a positive association between each s.d. increase in LTL and all (multivariable-adjusted OR 1.11, 95% CI: 1.01-1.22), low-grade (OR 1.13, 95% CI:1.01-1.27), and localised (OR 1.12, 95% CI:1.01-1.24) prostate cancer. Associations for other subtypes were similar, but did not reach statistical significance. In subgroup analyses, associations for high grade and advanced stage (OR=2.04, 95% CI 1.00-4.17; Pinteraction=0.06) or lethal disease (OR=2.37, 95% CI 1.19-4.72; Pinteraction=0.01) were stronger in men with a family history of the disease compared with those without. The minor allele of SNP, rs7726159, which has previously been shown to be positively associated with LTL, showed an inverse association with all prostate cancer risk after correction for multiple testing (P=0.0005).ConclusionIn this prospective study, longer LTL was modestly associated with higher risk of prostate cancer. A stronger association for more aggressive cancer in men with a family history of the disease needs to be confirmed in larger studies.