Contact UsGenome health: definition and processes
Maintaining integrity of the genome is fundamental to health at all stages of the life-cycle. Evidence for the association between elevated genome damage rate with increased risk for infertility, developmental defects, cancer and neurodegenerative disease is compelling (1-3). Although, to a certain degree, genome damage rate is affected by inherited defects in genes coding for DNA repair, cell cycle checkpoints, and antioxidant enzymes it is becoming increasingly evident that such defects may be acquired due to deficiency in cofactors required for DNA synthesis and repair enzymes and as a result of silencing of such genes due to altered genome methylation (1-4).
Nutrigenomics and genome health
Numerous cofactors are required for DNA synthesis and repair (e.g. Mg as co-factor for DNA polymerases, Zn as an integral part of the glycosylase OGG1 required for repair of oxidised guanine, vitamin B12 as cofactor for synthesis of tetrahydrofolate and methionine which are required ultimately for synthesis of dTTP and maintenance methylation of CpG respectively). Furthermore, dietary anti-inflammatory substances may help to minimise oxidative DNA damage induced endogenously by an overactive immune system (5). Importantly it has been shown that moderate differences in micronutrient concentration within the physiological range can cause as much genome damage as significant doses of ionising radiation and that sensitivity to environmental genotoxins is enhanced when cells are deficient in key nutrients such as folate (3). The accumulating evidence indicates quite clearly that sub-optimal dietary choices may have significant impacts on genome damage rate in populations and in individuals. The field of study relating to how dietary patterns and/or specific dietary factors impact on genome maintenance is known as Genome Health Nutrigenomics (3). An ultimate goal of this field of study is to define the optimal daily dietary intake levels and upper safety limits for each micro- and macro-nutrient using validated genome damage biomarkers.
The State of the Field and Needs
Ideally dietary advice for optimal genome health maintenance should be provided on an individual basis given that the ability to absorb and metabolise nutrients and DNA repair capacity can vary considerably between individuals. At this stage our knowledge is not refined enough to provide advice based on genotype for example of DNA repair or folate metabolism genes however large data bases are being accumulated world-wide on the relationships of these genotypes with established biomarkers of genome damage such as the cytokinesis-block micronucleus assay and assays that specifically measure oxidised bases in DNA. There is also a need for in vitro modelling and placebo-controlled interventions to identify which genotypes respond best to which dietary patterns and micronutrient supplements in terms of genome health maintenance. Therefore, there is also considerable scope for the emerging field of Genome Health Nutrigenetics but progress will only occur rapidly once a set of key genome health biomarkers are used uniformly in laboratories world-wide; the micronucleus, comet and DNA methylation and base damage assays are probably the best advanced for this purpose.
The Potential and Promise
Implementation of a nutrigenomics and nutrigenetics approach to optimising genome health maintenance on an individual basis is feasible using established methods and based on current knowledge of the key nutrients that appear to have a significant relationship with genome damage rates in human populations. The concept that minimisation of genome damage rate by nutritional intervention is likely to reduce risk of diseases caused by genome instability seems plausible but has not yet been proven prospectively. Nevertheless, the idea of the Genome Health Clinic based on the diagnosis and nutritional treatment of genome damage on an individual basis has been proposed (3). Given the possibility that elevated genome damage may also be caused by environmental or life-style exposure, as well as genetic and nutritional deficiencies or excess it is anticipated that the skills of a Genome Health Nutrigenomics and Nutrigenetics practitioner would have to encompass, as a minimum, the fields of genetic toxicology, genetics and nutrition, and preferably operate harmoniously with physicians who increasingly are taking interest in these modern approaches to disease prevention and may themselves wish to adopt Genome Health Nutrigenomics and Nutrigenetics as part of their practice.
References
- Ames BN, Wakimoto P. Are vitamin and mineral deficiencies a major cancer risk? (2002) Nature Reviews Cancer 2: 694-704
- Fenech M. (2001) Recommended dietary allowances for genomic stability. Mutation Research 480-481: 51-54
- Fenech M (2005) The Genome Health Clinic and Genome Health Nutrigenomics concepts: diagnosis and nutritional treatment of genome and epigenome damage on an individual basis. Mutagenesis 20: 55-69
- Fenech M. et al. (2005) Low intake of calcium, folate, nicotinic acid, vitamin E, retinol, β-carotene and high intake of pantothenic acid, biotin and riboflavin are significantly associated with increased genome instability – results from a dietary intake and micronucleus index survey in South Australia. Carcinogenesis 26: 991-999
- Surh Y., Kundu J.K., Na H.K., Lee J.D. (2005) Redox-sensitive transcription factors as prime targets for chemoprevention with anti-inflammatory and antioxidative phytochemicals. Journal of Nutrition 135: 2993S-3001S
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