Role of Key Micronutrients from Nutrigenetic and Nutrigenomic Perspectives in Cancer Prevention

Abstract

Regarding cancer as a genetic multi-factorial disease, a number of aspects need to be investigated and analyzed in terms of cancer's predisposition, development and prognosis. One of these multi-dimensional factors, which has gained increased attention in the oncological field due to its unelucidated role in risk assessment for cancer, is diet. Moreover, as studies advance, a clearer connection between diet and the molecular alteration of patients is becoming identifiable and quantifiable, thereby replacing the old general view associating specific phenotypical changes with the differential intake of nutrients. Respectively, there are two major fields concentrated on the interrelation between genome and diet: nutrigenetics and nutrigenomics. Nutrigenetics studies the effects of nutrition at the gene level, whereas nutrigenomics studies the effect of nutrients on genome and transcriptome patterns. By precisely evaluating the interaction between the genomic profile of patients and their nutrient intake, it is possible to envision a concept of personalized medicine encompassing nutrition and health care. The list of nutrients that could have an inhibitory effect on cancer development is quite extensive, with evidence in the scientific literature. The administration of these nutrients showed significant results in vitro and in vivo regarding cancer inhibition, although more studies regarding administration in effective doses in actual patients need to be done.

Keywords: cancer; chemoprevention; nutrigenetics; nutrigenomics.

Figure 1

Nutrients’ molecular targets and their intermediaries associated with the hallmarks of cancer. The major impact of nutrients is through their action on reactive oxygen species (ROS) production, which has a critical role in tumor-promoting inflammation. Aside from this effect, nutrients have been shown to effect multiple hallmarks of cancer: for example, fatty acids act on tumor-promoting inflammation, the induction of angiogenesis, the activation of invasion and metastasis and the sustenance of proliferative signaling. Other effects can be observed, significantly impacting on a person’s cancer susceptibility and prognosis, aspects of which can be modulated by patient diet in a directed manner, leading to the development of personalized nutrition.

Figure 2

Pathways or interactions representative of the metabolism of nutrients. The majority of the nutrients function either as electron transporters in redox systems or as ligands for transcription factors involved in gene regulation. These effects can be intertwined, as in the case of folate metabolism. Folate metabolism has a dual effect in that it facilitates protein methylation by providing 1-carbon source influencing gene regulation, and it acts in the redox system of oxidative stress by influencing the levels of homocysteine. GPx = glutathione peroxidase; GSH = reduced glutathione; GSSG = oxidized glutathione; GR = gluthatione reductase; NADP = nicotinamide dinucleotide phosphate; RAR = retinoic acid receptor; RXR = retinoid X receptor; RARE = retinoic acid response element; VDR = vitamin D receptor; VDRE = vitamin D response element; dUMP = deoxy uridine monophosphate; dTMP = deoxythymidine monophosphate; TYMS = thymidilatesynthetase; DHF = dihydrofolate; T/HF = tetrahydrofolate; MTHFR = methylene tetrahydrofolate reductase; MTHFD = methylene tetrahydrofolate dehydrogenase; MS = methionine synthetase; SAM = S-adenosyl methionine; SAH = S-adenosine homocysteine; MAT = methionine adenosine transferase; SAHH = S-adenylhomocisteine hydrolase.