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Circadian clock genes and risk of fatal prostate cancer

Markt, S.C., Valdimarsdottir, U.A., Shui, I.M., Sigurdardottir, L.G., Rider, J.R., Tamimi, R.M., Batista, J.L., Haneuse, S., Flynn-Evans, E., Lockley, S.W. , Czeisler, C.A., Stampfer, M.J., Launer, L., Harris, T., Smith, A.V., Gudnason, V., Lindstrom, S., Kraft, P. and Mucci, L.A. (2015) Circadian clock genes and risk of fatal prostate cancer Cancer Causes and Control, 26 (1). pp. 25-33.

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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. © 2014, Springer International Publishing Switzerland.

Item Type: Article
Authors :
Markt, S.C.
Valdimarsdottir, U.A.
Shui, I.M.
Sigurdardottir, L.G.
Rider, J.R.
Tamimi, R.M.
Batista, J.L.
Haneuse, S.
Flynn-Evans, E.
Czeisler, C.A.
Stampfer, M.J.
Launer, L.
Harris, T.
Smith, A.V.
Gudnason, V.
Lindstrom, S.
Kraft, P.
Mucci, L.A.
Date : 2015
DOI : 10.1007/s10552-014-0478-z
Uncontrolled Keywords : Circadian genes, Genetic polymorphisms, Prostate cancer, 6 hydroxymelatonin o sulfate, aged, Article, cancer risk, circadian rhythm, cohort analysis, controlled study, CRY1 gene, CSNK1E gene, fatality, gene, genetic association, genetic risk, hormone urine level, human, major clinical study, male, NPAS2 gene, PER3 gene, priority journal, prospective study, prostate cancer, risk assessment, single nucleotide polymorphism, TIMELESS gene, Caucasian, circadian rhythm, follow up, genetic predisposition, genetic variation, genetics, Iceland, middle aged, prostate tumor, risk factor, single nucleotide polymorphism, Aged, Circadian Clocks, Circadian Rhythm, European Continental Ancestry Group, Follow-Up Studies, Genetic Predisposition to Disease, Genetic Variation, Humans, Iceland, Male, Middle Aged, Polymorphism, Single Nucleotide, Prostatic Neoplasms, Risk Factors
Depositing User : Clive Harris
Date Deposited : 17 Jun 2020 01:18
Last Modified : 17 Jun 2020 01:18

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