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A prospective study of leukocyte telomere length and risk of renal cell carcinoma.

ABSTRACT: BACKGROUND:It has been hypothesized that genomic instability related to telomere dysfunction may contribute to carcinogenesis. There is some evidence from case-control studies suggesting that short leukocyte telomere length may be associated with an increased risk of renal cell carcinoma (RCC); however, this association has not been investigated prospectively. METHODS:We conducted a nested case-control study (209 cases, 410 controls) of RCC risk in relation to prediagnostic leukocyte telomere length in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. ORs and 95% confidence intervals (CI) were estimated using conditional logistic regression. RESULTS:Leukocyte telomere length was not significantly associated with future risk of RCC (highest quartile vs. lowest: OR, 0.8; 95% CI, 0.5-1.5; Ptrend = 0.6). Analyses stratified by sex, age, and time from blood collection to RCC diagnosis were similarly null. CONCLUSIONS:The results of this study, to our knowledge the first prospective investigation of its kind, do not support an association between prediagnostic leukocyte telomere length and risk of RCC. IMPACT:In contrast to some earlier reports, our findings add to the evidence that leukocyte telomere length is not a biomarker of risk related to the etiology of RCC.

SUBMITTER: Hofmann JN

PROVIDER: S-EPMC3655903 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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A prospective study of leukocyte telomere length and risk of renal cell carcinoma.

Hofmann Jonathan N JN Lan Qing Q Cawthon Richard R Hosgood H Dean HD Shuch Brian B Moore Lee E LE Rothman Nathaniel N Chow Wong-Ho WH Purdue Mark P MP

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20130319 5

<h4>Background</h4>It has been hypothesized that genomic instability related to telomere dysfunction may contribute to carcinogenesis. There is some evidence from case-control studies suggesting that short leukocyte telomere length may be associated with an increased risk of renal cell carcinoma (RCC); however, this association has not been investigated prospectively.<h4>Methods</h4>We conducted a nested case-control study (209 cases, 410 controls) of RCC risk in relation to prediagnostic leukoc ...[more]

PMID: 23513041

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Project description:IntroductionTelomeres and telomerase play important role in maintaining chromosome integrity and genomic stability. Recent epidemiologic data showed inconsistent findings which suggested that both short and long leukocyte telomeres could be associated with increased risk of pancreatic cancer. We prospectively examined the association between telomere length and pancreatic cancer risk in a population-based cohort study.MethodsThe Singapore Chinese Health Study recruited 63,257 Chinese aged 45 to 74 years from 1993 to 1998 in Singapore. Relative telomere length in peripheral blood leukocytes was quantified using a validated monochrome multiplex quantitative polymerase chain reaction method in 26,540 participants, including 116 participants who later developed pancreatic cancer after an average of 13 years of follow-up. Cox proportional hazard regression method was used to calculate hazard ratio (HR) and its 95% confidence interval (CI) of pancreatic cancer risk associated with telomere length, with adjustment for confounding factors.ResultsLonger telomeres were significantly associated with higher risk of pancreatic cancer (Ptrend = 0.02). Compared with lowest quartile, subjects with highest quartile of telomere length had an HR of 2.18 (95% CI: 1.25-3.80) for developing pancreatic cancer. In stratified analysis, this association remained among pancreatic adenocarcinoma patients but not among pancreatic non-adenocarcinoma patients. In continuous scale, the HRs and 95% CIs were 3.08 (1.17-8.11) for adenocarcinoma patients and 1.47 (0.43-5.06) for non-adenocarcinoma patients. The HRs and 95% CIs of the highest quartile of telomere length, compared with the lowest quartile, for adenocarcinoma and non-adenocarcinoma were 2.50 (1.22-5.13) and 1.63 (0.66-4.03), respectively. The length of follow-up from the collection of blood for the measurement of telomere length to the diagnosis of cancer (median = 8.0, range: from 5.0 months to 16.2 years) had no significant impact on the association between telomere length and pancreatic cancer risk.ConclusionsThe present study demonstrates that longer telomeres are associated with increased risk of overall pancreatic cancer.

Project description:Maintenance of telomere length has long been established to play a role in the biology of cancer and several studies suggest that it may be especially important in myeloid malignancies. To overcome potential bias in confounding and reverse causation of observational studies, we use both a polygenic risk score (PRS) and inverse-variance weighted (IVW) Mendelian randomization (MR) analyses to estimate the relationship between genetically predicted leukocyte telomere length (LTL) and acute myeloid leukemia (AML) risk in 498 cases and 2099 controls and myelodysplastic syndrome (MDS) risk in 610 cases and 1759 controls. Genetic instruments derived from four recent studies explaining 1.23-4.57% of telomere variability were considered. We used multivariable logistic regression to estimate odds ratios (OR, 95% confidence intervals [CI]) as the measure of association between individual single-nucleotide polymorphisms and myeloid malignancies. We observed a significant association between a PRS of longer predicted LTL and AML using three genetic instruments (OR = 4.03 per ~1200 base pair [bp] increase in LTL, 95% CI: 1.65, 9.85 using Codd et al. [Codd, V., Nelson, C.P., Albrecht, E., Mangino, M., Deelen, J., Buxton, J.L., Hottenga, J.J., Fischer, K., Esko, T., Surakka, I. et al. (2013) Identification of seven loci affecting mean telomere length and their association with disease. Nat. Genet., 45, 422-427 427e421-422.], OR = 3.48 per one-standard deviation increase in LTL, 95% CI: 1.74, 6.97 using Li et al. [Li, C., Stoma, S., Lotta, L.A., Warner, S., Albrecht, E., Allione, A., Arp, P.P., Broer, L., Buxton, J.L., Alves, A.D.S.C. et al. (2020) Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length. Am. J. Hum. Genet., 106, 389-404.] and OR = 2.59 per 1000 bp increase in LTL, 95% CI: 1.03, 6.52 using Taub et al. [Taub, M.A., Conomos, M.P., Keener, R., Iyer, K.R., Weinstock, J.S., Yanek, L.R., Lane, J., Miller-Fleming, T.W., Brody, J.A., Raffield, L.M. et al. (2022) Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed. Cell Genom., 2.] genetic instruments). MR analyses further indicated an association between LTL and AML risk (PIVW ≤ 0.049) but not MDS (all PIVW ≥ 0.076). Findings suggest variation in genes relevant to telomere function and maintenance may be important in the etiology of AML but not MDS.

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A prospective study of leukocyte telomere length and risk of renal cell carcinoma.

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A prospective study of leukocyte telomere length and risk of renal cell carcinoma.

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