Abstract
Purpose
Recent studies suggest variation in genes along the vitamin D pathway, as well as vitamin D receptor (VDR) protein levels, may be associated with prostate cancer. As serum vitamin D levels vary by season, we sought to determine whether the expression of genes on the vitamin D pathway, assessed in prostate tumor tissue, do the same.
Methods
Our study incorporates mRNA expression data from 362 men in the Swedish Watchful Waiting cohort, diagnosed between 1977 and 1999, and 106 men enrolled in the US Physicians’ Health Study (PHS) diagnosed between 1983 and 2004. We also assayed for VDR protein expression among 832 men in the PHS and Health Professionals Follow-up Study cohorts. Season was characterized by date of initial tissue specimen collection categorically and by average monthly ultraviolet radiation levels. One-way analysis of variance was used to examine variation in the expression levels of six genes on the vitamin D pathway—VDR, GC, CYP27A1, CYP27B1, RXRα, CYP24A1—and VDR protein by season, adjusted for age at diagnosis and Gleason grade. Variation was also examined separately among lethal and nonlethal cases.
Results
Tumor expression levels of the six genes did not vary significantly by season of tissue collection. No consistent patterns emerged from subgroup analyses by lethal versus nonlethal cases.
Conclusions
Unlike circulating levels of 25(OH) vitamin D, expression levels of genes on the vitamin D pathway and VDR protein did not vary overall by season of tissue collection. Epidemiological analyses of vitamin D gene expression may not be biased by seasonality.
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References
Ingles SA, Ross RK, Yu MC et al (1997) Association of prostate cancer risk with genetic polymorphisms in vitamin D receptor and androgen receptor. J Natl Cancer Inst 89(2):166–170
Holt SK, Kwon EM, Koopmeiners JS et al (2010) Vitamin D pathway gene variants and prostate cancer prognosis. Prostate 70(13):1448–1460
Chen L, Davey Smith G, Evans DM et al. (2009) Genetic variants in the vitamin d receptor are associated with advanced prostate cancer at diagnosis: findings from the prostate testing for cancer and treatment study and a systematic review. Cancer Epidemiol Biomarkers Prev 18(11):2874–2881
Shui IM, Mucci LA, Kraft P et al (2012) Vitamin D related genetic variation, plasma vitamin D, and risk of lethal prostate cancer. J Natl Cancer Inst 104(9):690–699
Schwartz GG, Whitlatch LW, Chen TC et al (1998) Human prostate cells synthesize 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3. Cancer Epidemiol Biomarkers Prev 7(5):391–395
Deeb KK, Trump DL, Johnson CS (2007) Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nat Rev Cancer 7(9):684–700
Webb AR, Kline L, Holick MF (1988) Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. J Clin Endocrinol Metab 67(2):373–378
Kimlin MG (2008) Geographic location and vitamin D synthesis. Mol Aspects Med 29(6):453–461
Savolainen K, Maenpaa PH, Alhava EM et al (1980) A seasonal difference in serum 25-hydroxyvitamin D3 in a Finnish population. Med Biol 58(1):49–52
McCullough ML, Weinstein SJ, Freedman DM et al (2010) Correlates of circulating 25-hydroxyvitamin D: cohort consortium vitamin D pooling project of rarer cancers. Am J Epidemiol 172(1):21–35
Pedersen JI (2008) Vitamin D requirement and setting recommendation levels—current Nordic view. Nutr Rev 66(10 Suppl 2):S165–S169
Hendrickson WK, Flavin R, Kasperzyk JL et al (2011) Vitamin d receptor protein expression in tumor tissue and prostate cancer progression. J Clin Oncol 29(17):2378–2385
Setlur SR, Mertz KD, Hoshida Y et al (2008) Estrogen-dependent signaling in a molecularly distinct subclass of aggressive prostate cancer. J Natl Cancer Inst 100(11):815–825
Sboner A, Demichelis F, Calza S et al (2010) Molecular sampling of prostate cancer: a dilemma for predicting disease progression. BMC Med Genomics 3:8
Hennekens CH, Buring JE, Manson JE et al (1996) Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med 334(18):1145–1149
Final report on the aspirin component of the ongoing Physicians’ Health Study (1989) Steering Committee of the Physicians’ Health Study Research Group. N Engl J Med 21(3):129–135
Giovannucci E, Ascherio A, Rimm EB et al (1995) Intake of carotenoids and retinol in relation to risk of prostate cancer. J Natl Cancer Inst 87(23):1767–1776
Fan JB, Yeakley JM, Bibikova M et al (2004) A versatile assay for high-throughput gene expression profiling on universal array matrices. Genome Res 14(5):878–885
Bibikova M, Yeakley JM, Chudin E et al (2004) Gene expression profiles in formalin-fixed, paraffin-embedded tissues obtained with a novel assay for microarray analysis. Clin Chem 50(12):2384–2386
US Environmental Protection Agency (2010) Monthly average UV index. US Environmental Protection Agency [cited 2011 September 20]; Available from: http://www.epa.gov/sunwise/uvimonth.html
The Swedish Radiation Safety Authority (SSM) (2010) Report from the SSM’s Scientific Council on Ultraviolet Radiation 2010 [2011:14 Rapport från SSM:s vetenskapliga råd om ultraviolett strålning 2010]. Stockholm, Sweden
Giovannucci E (2005) The epidemiology of vitamin D and cancer incidence and mortality: a review (United States). Cancer Causes Control 16(2):83–95
Holmberg L, Adolfsson J, Mucci L et al (2009) Season of diagnosis and prognosis in breast and prostate cancer. Cancer Causes Control 20(5):663–670
Stark JR, Perner S, Stampfer MJ et al (2009) Gleason score and lethal prostate cancer: does 3 + 4 = 4 + 3? J Clin Oncol 27(21):3459–3464
Acknowledgments
The authors would like to thank Natalie DuPré, Hannah Mandel, Lauren McLaughlin, and Colleen Evans for their assistance gathering data for this analysis. We are also grateful to the participants in the Physicians’ Health Study, the Health Professionals Follow-up Study, and the Swedish Watchful Waiting Cohort. This research was supported by the National Institutes of Health research training grant R25 CA098566 (MME) and training grant NIH 5 T32 CA09001-35 (JLK, KLP, IMS), National Cancer Institute grant CA141298 (MJS), the Prostate Cancer Foundation (LAM), and by the American Institute for Cancer Research (JLK). The Health Professionals Follow-Up Study is supported by NCI/NIH Grant P01 CA055075.
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The authors declare that they have no conflict of interest.
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Epstein, M.M., Andrén, O., Kasperzyk, J.L. et al. Seasonal variation in expression of markers in the vitamin D pathway in prostate tissue. Cancer Causes Control 23, 1359–1366 (2012). https://doi.org/10.1007/s10552-012-0016-9
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DOI: https://doi.org/10.1007/s10552-012-0016-9