Circadian clock genes and risk of fatal prostate cancer

• Published in: Cancer causes & control Vol. 26; no. 1; pp. 25 - 33
• Main Authors: Markt, Sarah C., Valdimarsdottir, Unnur A., Shui, Irene M., Sigurdardottir, Lara G., Rider, Jennifer R., Tamimi, Rulla M., Batista, Julie L., Haneuse, Sebastien, Flynn-Evans, Erin, Lockley, Steven W., Czeisler, Charles A., Stampfer, Meir J., Launer, Lenore, Harris, Tamara, Smith, Albert Vernon, Gudnason, Vilmundur, Lindstrom, Sara, Kraft, Peter, Mucci, Lorelei A.
• Format: Journal Article
• Language: English
• Published: Cham Springer 01-01-2015; Springer International Publishing; Springer Nature B.V
• Subjects: Aged; Apoptosis; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell cycle; Circadian Clocks - genetics; Circadian rhythm; Circadian Rhythm - genetics; DNA damage; Epidemiology; Follow-Up Studies; Genes; Genetic Predisposition to Disease; Genetic Variation; Genomes; Hematology; Humans; Iceland; Kinases; Male; Medicin och hälsovetenskap; Medicine; Melatonin; Middle Aged; Oncology; Original Paper; Polymorphism, Single Nucleotide; Prostate cancer; Prostatic Neoplasms - genetics; Public Health; Risk Factors; White People - genetics; Iceland; United States > US; Circadian genes; Prostate cancer; Genetic polymorphisms
• ISSN: 0957-5243; 1573-7225; 1573-7225
• DOI: 10.1007/s10552-014-0478-z

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.