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Telomere Length Varies By DNA Extraction Method: Implications for Epidemiologic Research
Open accessPublished version of a preprint
Abstract
BACKGROUND: Both shorter and longer telomeres in peripheral blood leukocyte (PBL) DNA have been associated with cancer risk. However, associations remain inconsistent across studies of the same cancer type. This study compares DNA preparation methods to determine telomere length from patients with colorectal cancer. METHODS: We examined PBL relative telomere length (RTL) measured by quantitative PCR (qPCR) in 1,033 patients with colorectal cancer and 2,952 healthy controls. DNA was extracted with phenol/chloroform, PureGene, or QIAamp. RESULTS: We observed differences in RTL depending on DNA extraction method (P < 0.001). Phenol/chloroform-extracted DNA had a mean RTL (T/S ratio) of 0.78 (range 0.01-6.54) compared with PureGene-extracted DNA (mean RTL of 0.75; range 0.00-12.33). DNA extracted by QIAamp yielded a mean RTL of 0.38 (range 0.02-3.69). We subsequently compared RTL measured by qPCR from an independent set of 20 colorectal cancer cases and 24 normal controls in PBL DNA extracted by each of the three extraction methods. The range of RTL measured by qPCR from QIAamp-extracted DNA (0.17-0.58) was less than from either PureGene or phenol/chloroform (ranges, 0.04-2.67 and 0.32-2.81, respectively). CONCLUSIONS: RTL measured by qPCR from QIAamp-extracted DNA was less than from either PureGene or phenol/chloroform (P < 0.001). IMPACT: Differences in DNA extraction method may contribute to the discrepancies between studies seeking to find an association between the risk of cancer or other diseases and RTL.
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“(c) different results may derive from different DNA extraction and assay methods and different laboratories (Aubert et al., 2012; Aviv et al., 2011; Cunningham et al., 2013; Montpetit et al., 2014; Nieratschker et al., 2013);”
From Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging (2015) · cites this paper as Cunningham et al., 2013
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Cites
Telomere measurement by quantitative PCR
Cawthon, R. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.10.e47 · Cited by 3,550
Telomere length dynamics in human lymphocyte subpopulations measured by flow cytometry
Rufer, N., Dragowska, W. H., Thornbury, G., Roosnek, E. E., & Lansdorp, P. M. (1998) · Nature Biotechnology · doi:10.1038/nbt0898-743 · Cited by 551
Telomere length and risk of incident cancer and cancer mortality
Willeit, P., Willeit, J., Mayr, A., Weger, S., Oberhollenzer, F., Brandstätter, A., Kronenberg, F., & Kiechl, S. (2010) · JAMA · doi:10.1001/jama.2010.897 · Cited by 484
Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins
Martínez, P., & Blasco, M. A. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3025 · Cited by 468
The association of telomere length and cancer: a meta-analysis
Wentzensen, I. M., Mirabello, L., Pfeiffer, R. M., & Savage, S. A. (2011) · Cancer Epidemiology, Biomarkers & Prevention · doi:10.1158/1055-9965.epi-11-0005 · Cited by 458
What do we need to know about speciation?
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Newcomb, P. A., Baron, J. A., Cotterchio, M., Gallinger, S., Grove, J., Haile, R. W., Hall, D. C., Hopper, J. L., Jass, J. R., Marchand, L. L., et al. (2007) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-07-0648 · Cited by 389
Self-citationShortened Telomere Length Is Associated with Increased Risk of Cancer: A Meta-Analysis
Ma, H., Zhou, Z., Wei, S., Liu, Z., Pooley, K. A., Dunning, A. M., Svenson, U., Roos, G., Hosgood, H. D., Shen, M., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020466 · Cited by 376 · cited 1×
“9 PubMed (US Library of Medicine, Bethesda MD) using the terms “cancer and telomeres” and “cancer and telomere length”, and we cross-referenced these articles with those reported in two published meta-analyses of telomere length and cancer risk (25,31).”
MethodAviv, A., Hunt, S. C., Lin, J., Cao, X., Kimura, M., & Blackburn, E. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr634 · Cited by 343
Telomere Length, Cigarette Smoking, and Bladder Cancer Risk in Men and Women
McGrath, M., Wong, J. Y. Y., Michaud, D. S., Hunter, D. J., & Vivo, I. D. (2007) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-06-0961 · Cited by 336
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Telomere Biology and Human Phenotype
Turner, K. J., Vasu, V., & Griffin, D. K. (2019) · Cells · doi:10.3390/cells8010073 · Cited by 415
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Lin, J., & Epel, E. S. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101507 · Cited by 418
Telomere Length: A Review of Methods for Measurement
Montpetit, A. J., Alhareeri, A. A., Montpetit, M., Starkweather, A. R., Elmore, L. W., Filler, K., Mohanraj, L., Burton, C. W., Menzies, V. S., Lyon, D. E., et al. (2014) · Nursing Research · doi:10.1097/nnr.0000000000000037 · Cited by 293
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Metadata
- Authors
- Cunningham, J. M., Johnson, R. A., Litzelman, K., Skinner, H. G., Seo, S., Engelman, C. D., Vanderboom, R. J., Kimmel, G. W., Gangnon, R. E., Riegert-Johnson, D. L., Baron, J. A., Potter, J. D., Haile, R., Buchanan, D. D., Jenkins, M. A., Rider, D. N., Thibodeau, S. N., Petersen, G. M., & Boardman, L. A.
- Affiliations
- Dartmouth College (US)
- Authors' Affiliations: Departments of 1Laboratory Medicine and Pathology, 2Health Sciences Research, and 3Gastroenterology, Mayo Clinic College of Medicine; 4Mayo Clinic Cancer Center, 5Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota; Departments of 6Population Health Sciences, and 7Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin; 8University of Michigan, Ann Arbor, Michigan; 9Division of Gastroenterology, Mayo Clinic, Jacksonville, Florida; 10Biostatistics & Epidemiology, Geisel School of Medicine, Dartmouth University, Hanover, New Hampshire; 11Public Health Sciences Division, Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington; 12The Stanford Cancer Institute and Stanford School of Medicine, Department of Medicine, Stanford, California; 13Queensland Institute of Medical Research, Clive Berghofer Cancer Research Centre, Brisbane, Queensland; and 14Melbourn
- Corresponding author
- Boardman, Lisa A.
- ORCID
- Venue
- Cancer Epidemiology, Biomarkers & Prevention
- Published
- 2013-11-01
- Volume
- 22
- Issue
- 11
- Pages
- 2047-2054
- ISSN
- 1055-9965 (ISSN-L)
- 1538-7755
- PMC
- PMC3827976
- OpenAlex
- W2056176559
- Cited by
- 111
- References
- 50
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 6 · 2022: 5 · 2021: 4 · 2020: 8 · 2019: 11 · 2018: 11 · 2017: 15 · 2016: 15 · 2015: 12 · 2014: 15 · 2013: 2
- FWCI
- 10.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Epidemiology Biomarkers & Prevention (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (T35HL007690)
- National Cancer Institute (U01CA074799, U24CA074799, UM1CA167551, U01CA074794, CA-96-011, U01CA074806, P20CA102701, U01CA074783, U01CA074800, P50CA102701, U24CA097735, U24CA074794, U24CA074800, U24CA074783, R01CA132718, U01CA097735, P30CA015083, P30CA014520)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK084567)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- telomere length, DNA extraction methods, colorectal cancer, phenol-chloroform extraction, relative telomere length, measurement variability, cancer risk biomarkers
- MeSH terms
- DNA, DNA, Neoplasm, Female, Humans, Leukocytes, Male, Middle Aged, Colorectal Neoplasms, Epidemiologic Studies, Case-Control Studies, Telomere
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