Abstract
Purpose
Vitamin D may reduce telomere shortening through anti-inflammatory and anti-cell proliferation mechanisms. In women, higher plasma 25-hydroxyvitamin D (25(OH)D) has been shown to be associated with longer telomere length, but the relationship has not been assessed in men.
Methods
We conducted a cross-sectional analysis of 25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)2D) and relative leukocyte telomere length (LTL) among 2483 men [1832 men for 1,25(OH)2D] who were selected as cases and controls in three studies of telomeres and cancer nested within the Health Professionals Follow-up Study. We also genotyped 95 SNPs representing common genetic variation in vitamin D pathway genes. LTL was measured by quantitative PCR, and z-scores within each study were calculated. Associations were assessed by linear as well as logistic regression adjusting for age and other potential confounders.
Results
Age (P-trend < 0.0001), pack-years of smoking (P-trend = 0.04) and body mass index (P-trend = 0.05) were inversely associated with LTL. Neither 25(OH)D nor 1,25(OH)2D was associated with LTL (multivariable-adjusted P-trend 0.69 and 0.41, respectively, for the linear regression model). One SNP in the retinoid X receptor alpha gene was associated with long LTL (P = 0.0003).
Conclusions
In this cross-sectional study of men, 25(OH)D and 1,25(OH)2D were not associated with relative LTL.
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Abbreviations
- 25(OH)D:
-
25-Hydroxyvitamin D
- 1,25(OH)2D:
-
1,25-dihydroxyvitamin D
- CV:
-
Coefficients of variation
- FFQ:
-
Food frequency questionnaire
- HPFS:
-
Health Professionals Follow-up Study
- LTL:
-
Leukocyte telomere length
- MET:
-
Metabolic equivalent per week
- qPCR:
-
Quantitative PCR
- SNP:
-
Single nucleotide polymorphism
- VDR:
-
Vitamin D receptor
References
Deeb KK, Trump DL, Johnson CS (2007) Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nat Rev Cancer 7(9):684–700. doi:10.1038/nrc2196
Nagpal S, Na S, Rathnachalam R (2005) Noncalcemic actions of vitamin D receptor ligands. Endocr Rev 26(5):662–687. doi:10.1210/er.2004-0002
Holick MF (2007) Vitamin D deficiency. New Engl J Med 357(3):266–281. doi:10.1056/NEJMra070553
Artandi SE, DePinho RA (2010) Telomeres and telomerase in cancer. Carcinogenesis 31(1):9–18. doi:10.1093/carcin/bgp268
Houben JM, Moonen HJ, van Schooten FJ, Hageman GJ (2008) Telomere length assessment: biomarker of chronic oxidative stress? Free Radic Biol Med 44(3):235–246. doi:10.1016/j.freeradbiomed.2007.10.001
von Zglinicki T (2000) Role of oxidative stress in telomere length regulation and replicative senescence. Ann N Y Acad Sci 908:99–110
Prescott J, McGrath M, Lee IM, Buring JE, De Vivo I (2010) Telomere length and genetic analyses in population-based studies of endometrial cancer risk. Cancer 116(18):4275–4282. doi:10.1002/cncr.25328
Butt HZ, Atturu G, London NJ, Sayers RD, Bown MJ (2010) Telomere length dynamics in vascular disease: a review. Eur J Vasc Endovasc Surg 40(1):17–26. doi:10.1016/j.ejvs.2010.04.012
Provvedini DM, Tsoukas CD, Deftos LJ, Manolagas SC (1983) 1,25-dihydroxyvitamin D3 receptors in human leukocytes. Science (New York, NY) 221(4616):1181–1183
Liu JJ, Prescott J, Giovannucci E, Hankinson SE, Rosner B, Han J, De Vivo I (2013) Plasma vitamin D biomarkers and leukocyte telomere length. Am J Epidemiol 177(12):1411–1417. doi:10.1093/aje/kws435
Richards JB, Valdes AM, Gardner JP, Paximadas D, Kimura M, Nessa A, Lu X, Surdulescu GL, Swaminathan R, Spector TD, Aviv A (2007) Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women. Am J Clin Nutr 86(5):1420–1425
Gardner M, Bann D, Wiley L, Cooper R, Hardy R, Nitsch D, Martin-Ruiz C, Shiels P, Sayer AA, Barbieri M, Bekaert S, Bischoff C, Brooks-Wilson A, Chen W, Cooper C, Christensen K, De Meyer T, Deary I, Der G, Diez Roux A, Fitzpatrick A, Hajat A, Halaschek-Wiener J, Harris S, Hunt SC, Jagger C, Jeon HS, Kaplan R, Kimura M, Lansdorp P, Li C, Maeda T, Mangino M, Nawrot TS, Nilsson P, Nordfjall K, Paolisso G, Ren F, Riabowol K, Robertson T, Roos G, Staessen JA, Spector T, Tang N, Unryn B, van der Harst P, Woo J, Xing C, Yadegarfar ME, Park JY, Young N, Kuh D, von Zglinicki T, Ben-Shlomo Y (2014) Gender and telomere length: systematic review and meta-analysis. Exp Gerontol 51:15–27. doi:10.1016/j.exger.2013.12.004
Rimm EB, Stampfer MJ, Colditz GA, Giovannucci E, Willett WC (1990) Effectiveness of various mailing strategies among nonrespondents in a prospective cohort study. Am J Epidemiol 131(6):1068–1071
Wei EK, Giovannucci E, Fuchs CS, Willett WC, Mantzoros CS (2005) Low plasma adiponectin levels and risk of colorectal cancer in men: a prospective study. J Natl Cancer Inst 97(22):1688–1694. doi:10.1093/jnci/dji376
Hollis BW (1997) Quantitation of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D by radioimmunoassay using radioiodinated tracers. Methods Enzymol 282:174–186
Platz EA, Leitzmann MF, Hollis BW, Willett WC, Giovannucci E (2004) Plasma 1,25-dihydroxy- and 25-hydroxyvitamin D and subsequent risk of prostate cancer. CCC 15(3):255–265. doi:10.1023/B:CACO.0000024245.24880.8a
Rosner B, Cook N, Portman R, Daniels S, Falkner B (2008) Determination of blood pressure percentiles in normal-weight children: some methodological issues. Am J Epidemiol 167(6):653–666. doi:10.1093/aje/kwm348
Shui IM, Mucci LA, Kraft P, Tamimi RM, Lindstrom S, Penney KL, Nimptsch K, Hollis BW, Dupre N, Platz EA, Stampfer MJ, Giovannucci E (2012) Vitamin D-related genetic variation, plasma vitamin D, and risk of lethal prostate cancer: a prospective nested case-control study. J Natl Cancer Inst 104(9):690–699. doi:10.1093/jnci/djs189
Li M, Byth K, Eastman CJ (2007) Childhood overweight and obesity by socio-economic indexes for areas. Med J Aust 187(3):195
Cawthon RM (2002) Telomere measurement by quantitative PCR. Nucleic Acids Res 30(10):e47
Rosner B (1983) Percentage point for a generalized ESD many-outlier procedure. Technometrics 25:165–172
Aviv A, Chen W, Gardner JP, Kimura M, Brimacombe M, Cao X, Srinivasan SR, Berenson GS (2009) Leukocyte telomere dynamics: longitudinal findings among young adults in the Bogalusa Heart Study. Am J Epidemiol 169(3):323–329. doi:10.1093/aje/kwn338
McGrath M, Wong JY, Michaud D, Hunter DJ, De Vivo I (2007) Telomere length, cigarette smoking, and bladder cancer risk in men and women. Cancer Epidemiol Biomark Prevent 16(4):815–819. doi:10.1158/1055-9965.epi-06-0961
Nawrot TS, Staessen JA, Gardner JP, Aviv A (2004) Telomere length and possible link to X chromosome. Lancet 363(9408):507–510. doi:10.1016/s0140-6736(04)15535-9
Sun Q, Shi L, Prescott J, Chiuve SE, Hu FB, De VI, Stampfer MJ, Franks PW, Manson JE, Rexrode KM (2012) Healthy lifestyle and leukocyte telomere length in U.S. women. PLoS ONE 7(5):e38374. doi:10.1371/journal.pone.0038374
Valdes AM, Andrew T, Gardner JP, Kimura M, Oelsner E, Cherkas LF, Aviv A, Spector TD (2005) Obesity, cigarette smoking, and telomere length in women. Lancet 366(9486):662–664. doi:10.1016/s0140-6736(05)66630-5
Zannolli R, Mohn A, Buoni S, Pietrobelli A, Messina M, Chiarelli F, Miracco C (2008) Telomere length and obesity. Acta paediatrica (Oslo, Norway : 1992) 97(7):952–954. doi:10.1111/j.1651-2227.2008.00783.x
Henle ES, Han Z, Tang N, Rai P, Luo Y, Linn S (1999) Sequence-specific DNA cleavage by Fe2 + -mediated fenton reactions has possible biological implications. J Biol Chem 274(2):962–971
Aviv A (2009) Leukocyte telomere length: the telomere tale continues. Am J Clin Nutr 89(6):1721–1722. doi:10.3945/ajcn.2009.27807
von Zglinicki T (2002) Oxidative stress shortens telomeres. Trends Biochem Sci 27(7):339–344
Aviv A (2002) Telomeres, sex, reactive oxygen species, and human cardiovascular aging. J Mol Med (Berlin, Germany) 80(11):689–695. doi:10.1007/s00109-002-0377-8
Barrett EL, Richardson DS (2011) Sex differences in telomeres and lifespan. Aging Cell 10(6):913–921. doi:10.1111/j.1474-9726.2011.00741.x
Giovannucci E (2005) The epidemiology of vitamin D and cancer incidence and mortality: a review (United States). CCC 16(2):83–95. doi:10.1007/s10552-004-1661-4
Dawson MI, Xia Z (2012) The retinoid X receptors and their ligands. Biochim Biophys Acta 1:21–56. doi:10.1016/j.bbalip.2011.09.014
Acknowledgments
The authors would like to thank the participants and staff of the Health Professionals Follow-up Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors would also like to thank Channing Division of Network Medicine, Department of Medicine, Brigham, and Women’s Hospital and Harvard Medical School and in addition Pati Soule, Esther Orr and Hardeep Ranu for their laboratory assistance. The Health Professionals Follow-up Study is supported by an infrastructure grant from the National Institutes of Health/National Cancer Institute (UM1 CA167552). BJ is also supported by a grant from the Swedish Research Council for Health, Working Life and Welfare; IMS is supported by a Department of Defense Prostate Cancer Research Program fellowship; IDV is supported by Grant R01 CA082838 and ELG is supported by Grant R01 CA133891 from the National Cancer Institute.
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This study was approved by the Human Subjects Committee of the Harvard T. H. Chan School of Public Health (NIH/NCI R01 CA133891), and written informed consent was obtained from all participants.
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Julin, B., Shui, I.M., Prescott, J. et al. Plasma vitamin D biomarkers and leukocyte telomere length in men. Eur J Nutr 56, 501–508 (2017). https://doi.org/10.1007/s00394-015-1095-7
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DOI: https://doi.org/10.1007/s00394-015-1095-7