Prospective Study of DNA Methylation at Chromosome 8q24 in Peripheral Blood and Prostate Cancer Risk

Overview

Journal Br J Cancer

Specialty Oncology

Date 2017 May 3

PMID 28463958

Citations 10

Authors

Kathryn Hughes Barry

Lee E Moore

Joshua N Sampson

Stella Koutros

Liying Yan

Ann Meyer

Mahitha Reddy

Andrew J Oler

Michael B Cook

Joseph F Fraumeni Jr

Meredith Yeager

Laufey T Amundadottir

Sonja I Berndt

Affiliations

Soon will be listed here.

Abstract

Background: Chromosome 8q24 has emerged as an important genetic susceptibility region for several cancers, including prostate cancer; however, little is known about the contribution of DNA methylation in this region to risk.

Methods: We prospectively evaluated DNA methylation at 8q24 in relation to prostate cancer using pre-diagnostic blood samples from 694 prostate cancer cases (including 172 aggressive cases) and 703 controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We used logistic regression to estimate odds ratios and 95% confidence intervals.

Results: Although none remained significant after adjustment for multiple testing (q>0.05), of the 50 CpG sites meeting quality control, we identified 8 sites that were nominally associated with prostate cancer (P<0.05), including 6 correlated (Spearman ρ: 0.20-0.52) sites in POU5F1B and 2 intergenic sites (most significant site: Chr8:128428897 in POU5F1B, P=0.01). We also identified two correlated (ρ=0.39) sites in MYC (Chr8:128753187 and Chr8:128753154) that were associated with aggressive (P=0.02 and 0.03), but not non-aggressive disease (P=0.70 and 0.20; P=0.01 and 4.6 × 10). These findings persisted after adjustment for the top 8q24 prostate cancer variants in our study.

Conclusions: Although requiring replication, our findings provide some evidence that 8q24 DNA methylation levels may be associated with prostate cancer risk.

Citing Articles

Firefighting, per- and polyfluoroalkyl substances, and DNA methylation of genes associated with prostate cancer risk.

Quaid M, Goodrich J, Calkins M, Graber J, Urwin D, Gabriel J Environ Mol Mutagen. 2024; 65(1-2):55-66.

PMID: 38523457 PMC: 11006564. DOI: 10.1002/em.22589.

Exploring the effects of genetic variation on gene regulation in cancer in the context of 3D genome structure.

Osman N, Shawky A, Brylinski M BMC Genom Data. 2022; 23(1):13.

PMID: 35176995 PMC: 8851830. DOI: 10.1186/s12863-021-01021-x.

Epigenome-Wide Association Study of Prostate Cancer in African Americans Identifies DNA Methylation Biomarkers for Aggressive Disease.

Xu Y, Tsai C, Chang W, Han Y, Huang M, Pettaway C Biomolecules. 2021; 11(12).

PMID: 34944472 PMC: 8698937. DOI: 10.3390/biom11121826.

LncRNA CASC21 induces HGH1 to mediate colorectal cancer cell proliferation, migration, EMT and stemness.

Zhang C, E J, Yu E RNA Biol. 2021; 18(sup1):369-381.

PMID: 34375566 PMC: 8677029. DOI: 10.1080/15476286.2021.1950464.

Detection and relevance of epigenetic markers on ctDNA: recent advances and future outlook.

Lianidou E Mol Oncol. 2021; 15(6):1683-1700.

PMID: 33942482 PMC: 8169441. DOI: 10.1002/1878-0261.12978.

References

Haiman C, Patterson N, Freedman M, Myers S, Pike M, Waliszewska A . Multiple regions within 8q24 independently affect risk for prostate cancer. Nat Genet. 2007; 39(5):638-44. PMC: 2638766. DOI: 10.1038/ng2015. View

Zlotta A, Egawa S, Pushkar D, Govorov A, Kimura T, Kido M . Prevalence of prostate cancer on autopsy: cross-sectional study on unscreened Caucasian and Asian men. J Natl Cancer Inst. 2013; 105(14):1050-8. DOI: 10.1093/jnci/djt151. View

Ahmadiyeh N, Pomerantz M, Grisanzio C, Herman P, Jia L, Almendro V . 8q24 prostate, breast, and colon cancer risk loci show tissue-specific long-range interaction with MYC. Proc Natl Acad Sci U S A. 2010; 107(21):9742-6. PMC: 2906844. DOI: 10.1073/pnas.0910668107. View

Barry K, Moore L, Liao L, Huang W, Andreotti G, Poulin M . Prospective study of DNA methylation at LINE-1 and Alu in peripheral blood and the risk of prostate cancer. Prostate. 2015; 75(15):1718-25. PMC: 4535169. DOI: 10.1002/pros.23053. View

Laird P . The power and the promise of DNA methylation markers. Nat Rev Cancer. 2003; 3(4):253-66. DOI: 10.1038/nrc1045. View

Hazelett D, Rhie S, Gaddis M, Yan C, Lakeland D, Coetzee S . Comprehensive functional annotation of 77 prostate cancer risk loci. PLoS Genet. 2014; 10(1):e1004102. PMC: 3907334. DOI: 10.1371/journal.pgen.1004102. View

Koh C, Bieberich C, Dang C, Nelson W, Yegnasubramanian S, De Marzo A . MYC and Prostate Cancer. Genes Cancer. 2011; 1(6):617-28. PMC: 3092219. DOI: 10.1177/1947601910379132. View

Koutros S, Beane Freeman L, Berndt S, Andreotti G, Lubin J, Sandler D . Pesticide use modifies the association between genetic variants on chromosome 8q24 and prostate cancer. Cancer Res. 2010; 70(22):9224-33. PMC: 2982856. DOI: 10.1158/0008-5472.CAN-10-1078. View

Puto L, Benner C, Hunter T . The DAXX co-repressor is directly recruited to active regulatory elements genome-wide to regulate autophagy programs in a model of human prostate cancer. Oncoscience. 2015; 2(4):362-72. PMC: 4468322. DOI: 10.18632/oncoscience.152. View

10.

Moen E, Mariani C, Zullow H, Jeff-Eke M, Litwin E, Nikitas J . New themes in the biological functions of 5-methylcytosine and 5-hydroxymethylcytosine. Immunol Rev. 2014; 263(1):36-49. PMC: 6691509. DOI: 10.1111/imr.12242. View

11.

Amundadottir L, Sulem P, Gudmundsson J, Helgason A, Baker A, Agnarsson B . A common variant associated with prostate cancer in European and African populations. Nat Genet. 2006; 38(6):652-8. DOI: 10.1038/ng1808. View

12.

Olama A, Kote-Jarai Z, Giles G, Guy M, Morrison J, Severi G . Multiple loci on 8q24 associated with prostate cancer susceptibility. Nat Genet. 2009; 41(10):1058-60. DOI: 10.1038/ng.452. View

13.

Abecasis G, Auton A, Brooks L, DePristo M, Durbin R, Handsaker R . An integrated map of genetic variation from 1,092 human genomes. Nature. 2012; 491(7422):56-65. PMC: 3498066. DOI: 10.1038/nature11632. View

14.

Breyer J, Dorset D, Clark T, Bradley K, Wahlfors T, McReynolds K . An expressed retrogene of the master embryonic stem cell gene POU5F1 is associated with prostate cancer susceptibility. Am J Hum Genet. 2014; 94(3):395-404. PMC: 3951923. DOI: 10.1016/j.ajhg.2014.01.019. View

15.

Polak P, Lawrence M, Haugen E, Stoletzki N, Stojanov P, Thurman R . Reduced local mutation density in regulatory DNA of cancer genomes is linked to DNA repair. Nat Biotechnol. 2013; 32(1):71-5. PMC: 4116484. DOI: 10.1038/nbt.2778. View

16.

Sotelo J, Esposito D, Duhagon M, Banfield K, Mehalko J, Liao H . Long-range enhancers on 8q24 regulate c-Myc. Proc Natl Acad Sci U S A. 2010; 107(7):3001-5. PMC: 2840341. DOI: 10.1073/pnas.0906067107. View

17.

Toropainen S, Malinen M, Kaikkonen S, Rytinki M, Jaaskelainen T, Sahu B . SUMO ligase PIAS1 functions as a target gene selective androgen receptor coregulator on prostate cancer cell chromatin. Nucleic Acids Res. 2015; 43(2):848-61. PMC: 4333416. DOI: 10.1093/nar/gku1375. View

18.

Gudmundsson J, Sulem P, Manolescu A, Amundadottir L, Gudbjartsson D, Helgason A . Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24. Nat Genet. 2007; 39(5):631-7. DOI: 10.1038/ng1999. View

19.

Florath I, Butterbach K, Muller H, Bewerunge-Hudler M, Brenner H . Cross-sectional and longitudinal changes in DNA methylation with age: an epigenome-wide analysis revealing over 60 novel age-associated CpG sites. Hum Mol Genet. 2013; 23(5):1186-201. PMC: 3919014. DOI: 10.1093/hmg/ddt531. View

20.

Thomas G, Jacobs K, Yeager M, Kraft P, Wacholder S, Orr N . Multiple loci identified in a genome-wide association study of prostate cancer. Nat Genet. 2008; 40(3):310-5. DOI: 10.1038/ng.91. View