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01-01-2015 | Original paper

Circadian clock genes and risk of fatal prostate cancer

Authors: Sarah C. Markt, Unnur A. Valdimarsdottir, Irene M. Shui, Lara G. Sigurdardottir, Jennifer R. Rider, Rulla M. Tamimi, Julie L. Batista, Sebastien Haneuse, Erin Flynn-Evans, Steven W. Lockley, Charles A. Czeisler, Meir J. Stampfer, Lenore Launer, Tamara Harris, Albert Vernon Smith, Vilmundur Gudnason, Sara Lindstrom, Peter Kraft, Lorelei A. Mucci

Published in: Cancer Causes & Control | Issue 1/2015

Abstract

Purpose

Circadian genes may be involved in regulating cancer-related pathways, including cell proliferation, DNA damage response, and apoptosis. We aimed to assess the role of genetic variation in core circadian rhythm genes with the risk of fatal prostate cancer and first morning void urinary 6-sulfatoxymelatonin levels.

Methods

We used unconditional logistic regression to evaluate the association of 96 single-nucleotide polymorphisms (SNPs) across 12 circadian-related genes with fatal prostate cancer in the AGES-Reykjavik cohort (n = 24 cases), the Health Professionals Follow-Up Study (HPFS) (n = 40 cases), and the Physicians’ Health Study (PHS) (n = 105 cases). We used linear regression to evaluate the association between SNPs and first morning void urinary 6-sulfatoxymelatonin levels in AGES-Reykjavik. We used a kernel machine test to evaluate whether multimarker SNP sets in the pathway (gene based) were associated with our outcomes.

Results

None of the individual SNPs were consistently associated with fatal prostate cancer across the three cohorts. In each cohort, gene-based analyses showed that variation in the CRY1 gene was nominally associated with fatal prostate cancer (p values = 0.01, 0.01, and 0.05 for AGES-Reykjavik, HPFS, and PHS, respectively). In AGES-Reykjavik, SNPs in TIMELESS (four SNPs), NPAS2 (six SNPs), PER3 (two SNPs) and CSNK1E (one SNP) were nominally associated with 6-sulfatoxymelatonin levels.

Conclusion

We did not find a strong and consistent association between variation in core circadian clock genes and fatal prostate cancer risk, but observed nominally significant gene-based associations with fatal prostate cancer and 6-sulfatoxymelatonin levels.

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Fu L, Lee CC (2003) The circadian clock: pacemaker and tumour suppressor. Nat Rev Cancer 3(5):350–361PubMedCrossRef

Zhu Y et al (2009) Testing the circadian gene hypothesis in prostate cancer: a population-based case–control study. Cancer Res 69(24):9315–9322PubMedCentralPubMedCrossRef

Davis S, Mirick DK (2006) Circadian disruption, shift work and the risk of cancer: a summary of the evidence and studies in Seattle. Cancer Causes Control 17:539–545PubMedCrossRef

Blask DE (2009) Melatonin, sleep disturbance and cancer risk. Sleep Med Rev 13(4):257–264PubMedCrossRef

Costa G, Haus E, Stevens R (2010) Shift work and cancer—considerations on rationale, mechanisms, and epidemiology. Scand J Work Environ Health 36(2):163–179PubMedCrossRef

Buja A et al (2005) Cancer incidence among male military and civil pilots and flight attendants: an analysis on published data. Toxicol Ind Health 21(10):273–282PubMedCrossRef

Straif K et al (2007) Carcinogenicity of shift-work, painting, and fire-fighting. Lancet Oncol 8(12):1065–1066PubMedCrossRef

Parent ME et al (2012) Night work and the risk of cancer among men. Am J Epidemiol 176(9):751–759PubMedCrossRef

Sigurdardottir LG et al (2014) Urinary melatonin levels, sleep disruption, and risk of prostate cancer in elderly men. Eur Urol. doi:10.1016/j.eururo.2014.07.008

10.

Sigurdardottir LG et al (2012) Circadian disruption, sleep loss, and prostate cancer risk: a systematic review of epidemiologic studies. Cancer Epidemiol Biomarkers Prev 21:1002–1011PubMedCentralPubMedCrossRef

11.

Sigurdardottir LG et al (2013) Sleep disruption among older men and risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 22(5):872–879PubMedCentralPubMedCrossRef

12.

Kondratov RV, Gorbacheva VY, Antoch MP (2007) The role of mammalian circadian proteins in normal physiology and genotoxic stress responses. Curr Top Dev Biol 78:173–216PubMedCrossRef

13.

Young MW, Kay SA (2001) Time zones: a comparative genetics of circadian clocks. Nat Rev Genet 2(9):702–715PubMedCrossRef

14.

Utge SJ et al (2010) Systematic analysis of circadian genes in a population-based sample reveals association of TIMELESS with depression and sleep disturbance. PLoS One 5(2):e9259PubMedCentralPubMedCrossRef

15.

Slominski RM et al (2012) Melatonin membrane receptors in peripheral tissues: distribution and functions. Mol Cell Endocrinol 351(2):152–166PubMedCentralPubMedCrossRef

16.

Antoch MP, Kondratov RV, Takahashi JS (2005) Circadian clock genes as modulators of sensitivity to genotoxic stress. Cell Cycle 4(7):901–907PubMedCentralPubMedCrossRef

17.

Gauger MA, Sancar A (2005) Cryptochrome, circadian cycle, cell cycle checkpoints, and cancer. Cancer Res 65(15):6828–6834PubMedCrossRef

18.

Borgs L et al (2009) Cell “circadian” cycle: new role for mammalian core clock genes. Cell Cycle 8(6):832–837PubMedCrossRef

19.

Hua H et al (2006) Circadian gene mPer2 overexpression induces cancer cell apoptosis. Cancer Sci 97(7):589–596PubMedCentralPubMedCrossRef

20.

DeBruyne JP, Weaver DR, Reppert SM (2007) CLOCK and NPAS2 have overlapping roles in the suprachiasmatic circadian clock. Nat Neurosci 10(5):543–545PubMedCentralPubMedCrossRef

21.

Chu LW et al (2008) Variants in circadian genes and prostate cancer risk: a population-based study in China. Prostate Cancer Prostatic Dis 11(4):342–348PubMedCrossRef

22.

Lin DW et al (2011) Genetic variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes are prognostic markers of prostate cancer-specific mortality. Cancer Epidemiol Biomarkers Prev 20(9):1928–1936PubMedCentralPubMedCrossRef

23.

Harris TB et al (2007) Age, gene/environment susceptibility-Reykjavik Study: multidisciplinary applied phenomics. Am J Epidemiol 165(9):1076–1087PubMedCentralPubMedCrossRef

24.

Giovannucci E et al (2003) Nutritional predictors of insulin-like growth factor I and their relationships to cancer in men. Cancer Epidemiol Biomarkers Prev 12(2):84–89PubMed

25.

Schumacher FR et al (2011) Genome-wide association study identifies new prostate cancer susceptibility loci. Hum Mol Genet 20(19):3867–3875PubMedCentralPubMedCrossRef

26.

Iceland S (2011) (cited 2014). http://www.statice.is/

27.

Psaty BM et al (2009) Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Design of Prospective Meta-Analyses of Genome-Wide Association Studies From 5 Cohorts. Circ Cardiovasc Genet 2(1):73–80PubMedCentralPubMedCrossRef

28.

Murphy RA et al (2013) Candidate gene association study of BMI-related loci, weight, and adiposity in old age. J Gerontol A Biol Sci Med Sci 68(6):661–666

29.

Nalls MA et al (2011) Multiple loci are associated with white blood cell phenotypes. PLoS Genet 7(6):e1002113. doi:10.1371/journal.pgen.1002113

30.

Li Y et al (2009) Genotype imputation. Annu Rev Genomics Hum Genet 10:387–406PubMedCentralPubMedCrossRef

31.

Cochran WG (1954) The combination of estimates from different experiments Biometrics 10:101–129

32.

Evangelou E, Ioannidis JPA (2013) Meta-analysis methods for genome-wide association studies and beyond. Nat Rev Genet 14:379–389PubMedCrossRef

33.

Wu MC et al (2010) Powerful SNP-set analysis for case–control genome-wide association studies. Am J Hum Genet 86(6):929–942PubMedCentralPubMedCrossRef

34.

Lin X et al (2011) Kernel machine SNP-set analysis for censored survival outcomes in genome-wide association studies. Genet Epidemiol 35(7):620–631PubMedCentralPubMedCrossRef

35.

Kelly MA et al (2012) Circadian gene variants and susceptibility to type 2 diabetes: a pilot study. PLoS One 7(4):e32670. doi:10.1371/journal.pone.0032670

36.

Cao Q et al (2009) A role for the clock gene Per1 in prostate cancer. Cancer Res 69(19):7619–7625PubMedCentralPubMedCrossRef

37.

Hoffman AE et al (2008) The circadian gene NPAS2, a putative tumor suppressor, is involved in DNA damage response. Mol Cancer Res 6:1461–1468PubMedCentralPubMedCrossRef

38.

Zhu Y et al (2006) Does “clock” matter in prostate cancer? Cancer Epidemiol Biomarkers Prev 15(1):3–5PubMedCentralPubMedCrossRef

39.

Carpen JD et al (2005) A single-nucleotide polymorphism in the 5′-untranslated region of the hPER2 gene is associated with diurnal preference. J Sleep Res 14(3):293–297PubMedCrossRef

40.

Evans DS et al (2013) Common genetic variants in ARNTL and NPAS2 and at chromosome 12p13 are associated with objectively measured sleep traits in the elderly. Sleep 36(3):431–446

41.

Duffy JF, Wright KP (2005) Entrainment of the human circadian system by light. J Biol Rhythms 20:326–338PubMedCrossRef

Title: Circadian clock genes and risk of fatal prostate cancer
Authors: Sarah C. Markt
Unnur A. Valdimarsdottir
Irene M. Shui
Lara G. Sigurdardottir
Jennifer R. Rider
Rulla M. Tamimi
Julie L. Batista
Sebastien Haneuse
Erin Flynn-Evans
Steven W. Lockley
Charles A. Czeisler
Meir J. Stampfer
Lenore Launer
Tamara Harris
Albert Vernon Smith
Vilmundur Gudnason
Sara Lindstrom
Peter Kraft
Lorelei A. Mucci
Publication date: 01-01-2015
Publisher: Springer International Publishing
Published in: Cancer Causes & Control / Issue 1/2015
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI: https://doi.org/10.1007/s10552-014-0478-z

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