Behavioural causes of serious diseases

This page deals with the ways epigenetic modification of genes influences the development and maintenance of serious diseases. The rest of the website will be devoted to how behaviour alters genes through epigenetic change and contributes to schizophrenia and psychoses.

Cancer

Epigenetic modification plays a significant part in both the promotion and prevention of cancer. Epigenetic modification may prevent cancer by inhibiting oncogenes (cancer genes) (1) and promoter sites (2) . Conversely, it may promote cancer by inhibiting cancer suppressor genes (1,3) and promoting promoter sites (4) .

Epigenetic modification of genes can be the result of environmental factors such as pollution and behaviour. Exercise can prevent/treat cancer epigenetically (5).

In this website I will be concentrating on the behavioural factors which lead to epigenetic change.

Obesity and cancer

Hypermethylation of the oestrogen receptor gene (ESR1) gene has been shown to be linked to breast cancer and shown to be greater in obese women compared with those of normal weight (6). Methylation was found to be associated with adiposity (amount of body fat) and colorectal cancers (7).

I was an author on a Lancet paper about the risk of several cancers from obesity (8) and my own unpublished study about the mTOR pathway to the development of cancer. This pathway contains many cancer promoting epigenetic steps which are enhanced by obesity.

 

Coronary Vascular Disease (CVD)

Environmental factors which increase the risk of CVD act on the genome (genetic makeup) through epigenetic modification. Identifying markers for this epigenetic change has become more important recently for warning signs and potential medicinal targets (9) .

The factors which lead to epigenetic change (see epigenetic mechanisms) and consequently CVD include: smoking, nutrition, stress, obesity etc. (10,7,11- 12).

 

Schizophrenia (SC)

Schizophrenia risk is increased by the epigenetic changes (13) which may be caused by behaviour (14).

Over the next few pages I will concentrate on the factors which cause the epigenetic changes to the brain which result in schizophrenia.

 

References

1. Tan W, Liu B, Qu S, et al. MicroRNAs and cancer: Key paradigms in molecular therapy. Oncology Letters 2018;15(3):2735-42. doi: 10.3892/ol.2017.7638

2. Huang Y, Nayak S, Jankowitz R, et al. Epigenetics in breast cancer: what's new? Breast Cancer Research : BCR 2011;13(6):225-25. doi: 10.1186/bcr2925

3. Cheng Y, Geng H, Cheng SH, et al. KRAB Zinc Finger Protein ZNF382 Is a Proapoptotic Tumor Suppressor That Represses Multiple Oncogenes and Is Commonly Silenced in Multiple Carcinomas. Cancer Research 2010;70(16):6516-26. doi: 10.1158/0008-5472.can-09-4566

4. Cao B, Yang W, Jin Y, et al. Silencing NKD2 by Promoter Region Hypermethylation Promotes Esophageal Cancer Progression by Activating Wnt Signaling. Journal of Thoracic Oncology;11(11):1912-26. doi: 10.1016/j.jtho.2016.06.015

5. Paronetto MP, Dimauro I, Grazioli E, et al. Exercise-mediated downregulation of MALAT1 expression and implications in primary and secondary cancer prevention. Free Radic Biol Med 2020 doi: 10.1016/j.freeradbiomed.2020.06.037 [published Online First: 2020/08/10]

6. Daraei A, Izadi P, Khorasani G, et al. Epigenetic Changes of the ESR1 Gene in Breast Tissue of Healthy Women: A Missing Link with Breast Cancer Risk Factors? Genetic testing and molecular biomarkers 2017;21(8):464-70. doi: 10.1089/gtmb.2017.0028 [published Online First: 2017/07/15]

7. Campanella G, Gunter MJ, Polidoro S, et al. Epigenome-wide association study of adiposity and future risk of obesity-related diseases. International Journal of Obesity 2018 doi: 10.1038/s41366-018-0064-7

8. Renehan AG, Tyson M, Egger M, et al. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. The Lancet 2008;371(9612):569-78.

9. Abi Khalil C. The emerging role of epigenetics in cardiovascular disease. Therapeutic Advances in Chronic Disease 2014;5(4):178-87. doi: 10.1177/2040622314529325

10. Ordovás JM, Smith CE. Epigenetics and cardiovascular disease. Nature reviews Cardiology 2010;7(9):510-19. doi: 10.1038/nrcardio.2010.104

11. Wahl S, Drong A, Lehne B, et al. Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity. Nature 2017;541(7635):81-86. doi: 10.1038/nature20784

12. Junien C, Gallou-Kabani C, Vige A, et al. [Nutritional epigenomics of metabolic syndrome]. Med Sci (Paris) 2005;21(4):396-404.

13. Shorter KR, Miller BH. Epigenetic mechanisms in schizophrenia. Progress in Biophysics and Molecular Biology 2015;118(1–2):1-7. doi: http://dx.doi.org/10.1016/j.pbiomolbio.2015.04.008

14. Sweatt JD, Tamminga CA. An epigenomics approach to individual differences and its translation to neuropsychiatric conditions. Dialogues in Clinical Neuroscience 2016;18(3):289-98.