Nutritional Factors and Gender Influence Age-related DNA Methylation in the Human Rectal Mucosa

Overview

Journal Aging Cell

Specialties Cell Biology
Geriatrics

Date 2012 Nov 20

PMID 23157586

Citations 46

Authors

Henri S Tapp

Daniel M Commane

D Michael Bradburn

Ramesh Arasaradnam

John C Mathers

Ian T Johnson

Nigel J Belshaw

Affiliations

Soon will be listed here.

Abstract

Aberrant methylation of CpG islands (CGI) occurs in many genes expressed in colonic epithelial cells, and may contribute to the dysregulation of signalling pathways associated with carcinogenesis. This cross-sectional study assessed the relative importance of age, nutritional exposures and other environmental factors in the development of CGI methylation. Rectal biopsies were obtained from 185 individuals (84 male, 101 female) shown to be free of colorectal disease, and for whom measurements of age, body size, nutritional status and blood cell counts were available. We used quantitative DNA methylation analysis combined with multivariate modelling to investigate the relationships between nutritional, anthropometric and metabolic factors and the CGI methylation of 11 genes, together with LINE-1 as an index of global DNA methylation. Age was a consistent predictor of CGI methylation for 9/11 genes but significant positive associations with folate status and negative associations with vitamin D and selenium status were also identified for several genes. There was evidence for positive associations with blood monocyte levels and anthropometric factors for some genes. In general, CGI methylation was higher in males than in females and differential effects of age and other factors on methylation in males and females were identified. In conclusion, levels of age-related CGI methylation in the healthy human rectal mucosa are influenced by gender, the availability of folate, vitamin D and selenium, and perhaps by factors related to systemic inflammation.

Citing Articles

Vitamin D alleviates HFD-induced hepatic fibrosis by inhibiting DNMT1 to affect the TGFβ1/Smad3 pathway.

Liang Y, Jiang X, Zhao X, Tang T, Fan X, Wang R iScience. 2024; 27(12):111262.

PMID: 39713736 PMC: 11661986. DOI: 10.1016/j.isci.2024.111262.

Exploring sex differences: insights into gene expression, neuroanatomy, neurochemistry, cognition, and pathology.

Lafta M, Mwinyi J, Affatato O, Rukh G, Dang J, Andersson G Front Neurosci. 2024; 18:1340108.

PMID: 38449735 PMC: 10915038. DOI: 10.3389/fnins.2024.1340108.

Research progress of LINE-1 in the diagnosis, prognosis, and treatment of gynecologic tumors.

Fu J, Qin T, Li C, Zhu J, Ding Y, Zhou M Front Oncol. 2023; 13:1201568.

PMID: 37546391 PMC: 10399582. DOI: 10.3389/fonc.2023.1201568.

Colorectal cancer detected by liquid biopsy 2 years prior to clinical diagnosis in the HUNT study.

Brenne S, Madsen P, Pedersen I, Hveem K, Skorpen F, Krarup H Br J Cancer. 2023; 129(5):861-868.

PMID: 37438612 PMC: 10449868. DOI: 10.1038/s41416-023-02337-4.

Vitamin D as a Nutri-Epigenetic Factor in Autoimmunity-A Review of Current Research and Reports on Vitamin D Deficiency in Autoimmune Diseases.

Mazur A, Fraczek P, Tabarkiewicz J Nutrients. 2022; 14(20).

PMID: 36296970 PMC: 9611618. DOI: 10.3390/nu14204286.

References

Teschendorff A, Menon U, Gentry-Maharaj A, Ramus S, Weisenberger D, Shen H . Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer. Genome Res. 2010; 20(4):440-6. PMC: 2847747. DOI: 10.1101/gr.103606.109. View

Jones P, Baylin S . The fundamental role of epigenetic events in cancer. Nat Rev Genet. 2002; 3(6):415-28. DOI: 10.1038/nrg816. View

Chan A, Broaddus R, Houlihan P, Issa J, Hamilton S, Rashid A . CpG island methylation in aberrant crypt foci of the colorectum. Am J Pathol. 2002; 160(5):1823-30. PMC: 1850869. DOI: 10.1016/S0002-9440(10)61128-5. View

Armitage P, DOLL R . The age distribution of cancer and a multi-stage theory of carcinogenesis. Br J Cancer. 1954; 8(1):1-12. PMC: 2007940. DOI: 10.1038/bjc.1954.1. View

Ibrahim A, Arends M, Silva A, Wyllie A, Greger L, Ito Y . Sequential DNA methylation changes are associated with DNMT3B overexpression in colorectal neoplastic progression. Gut. 2010; 60(4):499-508. DOI: 10.1136/gut.2010.223602. View

Kemsley E, Le Gall G, Dainty J, Watson A, Harvey L, Tapp H . Multivariate techniques and their application in nutrition: a metabolomics case study. Br J Nutr. 2007; 98(1):1-14. DOI: 10.1017/S0007114507685365. View

Fiala E, Staretz M, Pandya G, El-Bayoumy K, Hamilton S . Inhibition of DNA cytosine methyltransferase by chemopreventive selenium compounds, determined by an improved assay for DNA cytosine methyltransferase and DNA cytosine methylation. Carcinogenesis. 1998; 19(4):597-604. DOI: 10.1093/carcin/19.4.597. View

Lee J, Li H, Chan A, Hollis B, Lee I, Stampfer M . Circulating levels of vitamin D and colon and rectal cancer: the Physicians' Health Study and a meta-analysis of prospective studies. Cancer Prev Res (Phila). 2011; 4(5):735-43. PMC: 3412303. DOI: 10.1158/1940-6207.CAPR-10-0289. View

Park J, Mitrou P, Keogh R, Luben R, Wareham N, Khaw K . Self-reported and measured anthropometric data and risk of colorectal cancer in the EPIC-Norfolk study. Int J Obes (Lond). 2011; 36(1):107-18. DOI: 10.1038/ijo.2011.61. View

10.

Belshaw N, Pal N, Tapp H, Dainty J, Lewis M, Williams M . Patterns of DNA methylation in individual colonic crypts reveal aging and cancer-related field defects in the morphologically normal mucosa. Carcinogenesis. 2010; 31(6):1158-63. DOI: 10.1093/carcin/bgq077. View

11.

Gregorieff A, Clevers H . Wnt signaling in the intestinal epithelium: from endoderm to cancer. Genes Dev. 2005; 19(8):877-90. DOI: 10.1101/gad.1295405. View

12.

Christensen B, Houseman E, Marsit C, Zheng S, Wrensch M, Wiemels J . Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet. 2009; 5(8):e1000602. PMC: 2718614. DOI: 10.1371/journal.pgen.1000602. View

13.

Al-Ghnaniem R, Peters J, Foresti R, Heaton N, Pufulete M . Methylation of estrogen receptor alpha and mutL homolog 1 in normal colonic mucosa: association with folate and vitamin B-12 status in subjects with and without colorectal neoplasia. Am J Clin Nutr. 2007; 86(4):1064-72. DOI: 10.1093/ajcn/86.4.1064. View

14.

Tapp H, Defernez M, Kemsley E . FTIR spectroscopy and multivariate analysis can distinguish the geographic origin of extra virgin olive oils. J Agric Food Chem. 2003; 51(21):6110-5. DOI: 10.1021/jf030232s. View

15.

Toyota M, Ahuja N, Herman J, Baylin S, Issa J . CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci U S A. 1999; 96(15):8681-6. PMC: 17576. DOI: 10.1073/pnas.96.15.8681. View

16.

Xiao Y, Word B, Starlard-Davenport A, Haefele A, Lyn-Cook B, Hammons G . Age and gender affect DNMT3a and DNMT3b expression in human liver. Cell Biol Toxicol. 2007; 24(3):265-72. DOI: 10.1007/s10565-007-9035-9. View

17.

Wallace K, Grau M, Levine A, Shen L, Hamdan R, Chen X . Association between folate levels and CpG Island hypermethylation in normal colorectal mucosa. Cancer Prev Res (Phila). 2010; 3(12):1552-64. PMC: 3058541. DOI: 10.1158/1940-6207.CAPR-10-0047. View

18.

Segditsas S, Sieber O, Rowan A, Setien F, Neale K, Phillips R . Promoter hypermethylation leads to decreased APC mRNA expression in familial polyposis and sporadic colorectal tumours, but does not substitute for truncating mutations. Exp Mol Pathol. 2008; 85(3):201-6. DOI: 10.1016/j.yexmp.2008.09.006. View

19.

Palmer H, Gonzalez-Sancho J, Espada J, Berciano M, Puig I, Baulida J . Vitamin D(3) promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of beta-catenin signaling. J Cell Biol. 2001; 154(2):369-87. PMC: 2150773. DOI: 10.1083/jcb.200102028. View

20.

Iacopetta B, Grieu F, Phillips M, Ruszkiewicz A, Moore J, Minamoto T . Methylation levels of LINE-1 repeats and CpG island loci are inversely related in normal colonic mucosa. Cancer Sci. 2007; 98(9):1454-60. PMC: 11158818. DOI: 10.1111/j.1349-7006.2007.00548.x. View