NUTRITION AND CANCER PREVENTION
NUTRITION and Cancer
It has been estimated that up to one-third of all cancer deaths may be attributable to dietary factors (1). There are about 25.000 bioactive food components known (2). Therefore reducing the risk of a disease (including cancer) with the use of food, find to achieve genetic potential and increase productivity seems a viable means (3). Antioxidants are compounds that neutralize reactive oxygen species (ROS), cure which in high amounts may damage cellular structures including DNA, health RNA, proteins, and lipids (4). Consumption of vegetable and dietary antioxidants can modify genetic susceptibility to cancer (4,5).
Lycopene is a carotenoid with antioxidant capacity and found in diet, blood and tissue. Lycopene is absorbed from the diet and transported by plasma lipoproteins. Carotenoids promote cell differentiation and inhibit cell proliferation. The effectiveness of lycopene is consistent with a vitamin A-independent pathway modulating cell function in vitro. This might be one mechanism for the anticancer activity of carotenoids as well as, by multiple conjugated double bonds, acting like scavenger for free radicals (6,7). Lycopene has been associated with reduced prostate cancer (PCa) risk in some studies.(8,9,10,11) Androgens can alter lycopene metabolism and in turn, lycopene seems to decrease the expression of androgen-producing enzymes and therefore, may alter androgen metabolism (10,12,13). Some lycopenoids, lycopene metabolites, inhibit proliferation, enhance cell-to-cell communication or induce apoptosis and, therefore, demonstrate anti-cancer activity.
Apoptosis is one of the key factors determining the fate of a cancer cell. Lycopene affects intracellular levels in addition to antioxidant function, e.g. cellular signaling, transcription factor activity and apoptosis. One transcription factor can be influenced by multiple components (14,15,).
FACTORS to Consider
Individuals respond differently to bioactive food components (16) and not all people respond identically according to baseline characteristics prior to supplementation, lowest versus highest tertiles (17). Internal and external markers need to be considered, e.g. baseline status prior to supplementation, dose and duration, smoking, genetics, interaction among dietary components and the chemical form of the antioxidant/food component and effect in the target tissue (18). Quantity of dietary components affects biological response and more is not always better (19,20). Foods are not just one-antioxidant but complex mixtures of components and nutrition is a question of balance (21). Tomatoes are not equal to lycopene as tomato powder inhibits PCa, but not lycopene (22). Tomato products may contain other compounds in addition to lycopene, which can modify prostate carcinogenesis. In an intervention trial with carotenoid-rich foods, cancer-protective effect via reduction in genetic damage in humans was observed (5).
The Literature Provides Mixed Conclusions
Lycopene supplements are not recommended, as they have not been proven to be effective for PCa treatment/prevention (23) despite positive outcomes in the past (24). Part of the confusion arises from trying to use population information to predict individual responses. Integrating the “OMICS” of nutrition to identify responders from non-responders and to investigate the health benefits of dietary constituents brings new insights regarding the biological mechanisms involved in cancer risk reduction properties of dietary constituents (25). Genomics can influence the response to diet at multiple points e.g. food tolerance, food preference, absorption, metabolism, transport and effect in target tissue (18). Heritability can influence food preference when using empirically derived grouping of foods (26).
Specific genes can influence what we like to eat e.g. a genetic variant in the glucose transporter type 2 (GLUT2) is associated with higher intake of sugars (27).
Bioavailability – Modest Correlation Between the Dietary Consumption and Lycopene Concentration in Blood
Lycopene concentration from processed tomato products is higher/more bioavailable than in fresh tomatoes (28). Individual consumption and serum lycopene levels can vary vastly (29). Absorption and distribution is influenced by dietary and genetic factors (16). There is variability in prospective studies between high versus low tomato intake or lycopene and PCa (24,30,31,32).
Epidemiological studies reveal different outcomes according to diet score and plasma level and therefore are poor predictors of blood lycopene concentrations at the individual level (29).
Susceptibility – Diet Can Modify Genetic Susceptibility to Cancer
Polyphenols can impact on DNA methylation, histone modification and regulation of expression of noncoding miRNAs, contributing towards their chemo-protective potential (33). Not all individuals respond equally to lycopene. Findings from Goodman et al (16 ) indicate that the association between lycopene and PCa is complex and may be modified by XRCC1 genotype and by other antioxidants. For Arg/Arg genotype men at codon 399, odds ratios (ORs) for PCa risk associated with medium and high lycopene intake were 0.9 and 0.21 (P <0.01). Similar analyses for men associated with Arg/Gln or Gln/Gln genotypes produced null results. Among men with the combination of Arg/Arg genotype, above-median lycopene intake combined with above-median intakes of ?-tocopherol and ?-carotene was associated with an OR of 0.11 (0.02-0.65), but not with men with at least one Gln allele (P(interaction)=0.01) (16).
Gene signature/expression changes in a human breast cancer cell lines (MCF-7 and MDA-MB 231) and a fibrocystic breast cell line (MCF-10a) treated with lycopene.
Lycopene seems to enhance cell cycle regulation, apoptosis, and DNA repair mechanisms according to estrogen and retinoic acid receptor cell status (34).
Interactions – Dietary Components and Timing of Initiation of Nutrients
The effect of micronutrient combinations and timing of initiation were examined on PCa development in the Lady transgenic model. Combination of vitamin E (E), selenium (Se), and lycopene (L) resulted in a significant reduction in PCa and liver metastasis when intervention was commenced within 8 weeks of age (P<0.0001). However, a combination of E+Se was not effective in preventing PCa but early commencement of micronutrients (E+Se+L) is beneficial in reducing PCa, with lycopene as an essential component of the combination, and effective for PCa prevention (35).
The Microbiome – Diet and the Intestinal Flora
Diet alters microbiotal activity, gene expression and modifies metabolic pathways (36). The microbiome influences metabolites in serum. Number of molecules, resulting from phase 2 drug-like chemical processing of microbial metabolites, were significantly elevated. The metabolic processing of indole-containing molecules may especially interact with the microbiome (37). Dias et al (38) evaluated whether a synergy exists for the combined treatment with synbiotic and lycopene on early biomarkers of colon carcinogenesis in rats. Lycopene, synbiotic or combined treatment reduced proliferating cell nuclear antigen (PCNA) and p53 protein labeling indexes, significantly increased apoptosis and reduced the development of classical aberrant crypt foci (ACF) and mucin-negative ACF (38).
Lycopene can influence a cancer process by complex means. The individual genome and the microbiota may determine the response to specific bioactive dietary ingredients or foods. One size does not fit all.
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