**4.4 Nutrigenomics and cancer**

*Mineral Deficiencies - Electrolyte Disturbances, Genes, Diet and Disease Interface*

individuals) have diabetes, and the number of individuals with this disease is expected to rise beyond 592 million in less than 25 years [86]. DM fall into two broad etiopathogenetic categories: type 1 and type 2 DM known as T1DM and T2DM, respectively. The epidemic global obesity noted by Prentice [87], he stated that virtually T2DM will be a major health issue in the world create a major drain on health budgets. Individual with obesity increases the risk of developing the disease DM by at least 10 fold as compared to normal one [88, 89]. In developing countries, peoples are shifted their lifestyle from traditional diets system to modernized fast food eating habit which include frequent consumption of red meat, refined carbohydrates and saturated fats is leads to obesity [90]. The insulin hormone, which is an important controller of glucose and fat metabolism is secreted from β-cells of pancreas. Irregular secretion insulin is observed in both the cases i.e. obesity and T2DM. Glucolipotoxicity is the results of high sugar and saturated fatty acid in diet on regular basis as suggested by Prentki et al. [91] and it negatively controls the secretion of insulin of from the β-cells, and results hyperglycemia and

Flavonoids present in the diets include flavones, flavonols, flavanones, isoflavones, and anthocyanins. Various experimental studies suggested the protective role of polyphenols on glucose homeostasis mechanism, along with this some specific molecules like flavanols, luteolin, quercetin and others have a great impact on different steps of intracellular signalling pathways (insulin secretion, insulin signalling and glucose uptake, enhancing mitochondrial status, suppression of inflammatory cytokine production and reactive oxygen species (ROS)/reactive nitrogen). In addition to flavonoids, phenolic acids and tannins also have inhibiting property of the enzyme α-glucosidase and α-amylase which is responsible for carbohydrate digestion [92–97]. For instance, Song et al. [98] noted that consumption of apple or tea was associated inversely with T2DM risk. This is in accordance with the Health Professionals Follow-Up Studies also suggested that higher consumption of anthocyanins, particularly from pears, apples and blueberries, were inversely associated

Caffeic acid, chlorogenic acid (present in coffee) and ferulic acid (esterified to hemicelluloses in cereals) are the most common phenolic acids [96]. An inverse result with caffeinated, decaffeinated coffee and caffeine intake with T2DM in a dose-response manner (1–6 cups/day), compared with no or rare coffee consumption was observed in different epidemiological studies, which support the hypothesis i.e. habitual coffee consumption is associated with a substantially lower risk of

Resveratrol (trans-3,5,4′-trihydroxystilbene) is a natural phenol act as an phytoalexins, found in the skin of grapes, blueberries, mulberries, raspberries, peanutsand red wine, helps in reducing the complications of diabetes in many organs and tissues including liver and pancreatic β-cells and in different diabetic animal models [102]. It also improve the glucose homeostasis and give protection to pancreatic β-cells. It has an important role in insulin secretion and amelioration of

Whereas, Afzal et al., [104] depicted that lower vitamin D levels represent a risk factor for incident of T2DM in humans. However, the levels of hypovitamin D along with increased levels of parathyroid hormone (PTH) is an independent predictor of β-cell dysfunction, insulin receptor and glycemia [105]. Patients with T2DM with established hypovitaminosis improve glycaemia and insulin secretion by Vitamin D replenishment, not only through a direct action on pancreatic β-cell function but also via regulation of plasma calcium levels, which regulate insulin synthesis and

**16**

hyperlipidemia.

with T2DM [99].

T2DM [100, 101].

metabolic disorders [103].

secretion [106, 107].

Cancer is a multiple stages process in which gene expression, and protein and metabolite function begin to run aberrantly [108]. In today's genomic era, the cellular events which intercede the activation of carcinogenesis upon modulation by dietary factors, has led to flow of significant information which helped in understanding of this disease [109]. Cancer susceptibility may increase due to inherited mutations in genes. Gene diet interaction may increase the risk of developing cancer. Endogenous reactions, such as oxidations or from exogenous agents, sunlight exposure (skin cancer), such as tobacco smoke (lung cancer), aflatoxin (liver cancer), and relatively high doses of ionizing radiations (many types of cancers) [110] induces cancer.

It is mandatory to have communication between nutrition, metabolism, and gene expression for upholding body homeostasis. Human genome and nutrition jointly interacts to do the same. Individual's health condition and susceptibility to disease may get affected due to this [111]. Nutrient regulates transcription factors at the molecular level which then modifies the gene expression (up or down), consequently to adjust the metabolic responses [112].

Diet is a blend of protective, carcinogenic, and mutagenic agents all together and are metabolized by the enzymes of biotransformation process. Risk of developing cancer can be modified through genetic polymorphisms that change protein expression or the function of these enzymes. Foods ingested by humans are proposed to contain more than 25,000 [113]. Role of different bioactive food ingredients in cancer pathogenesis has been studied and found that, among these, more than 500 types of bioactive food ingredients is proved to be possible predisposing agents.

For carcinogens, diet is considered as a source (intrinsic or cooking-generated) present in certain foods or constituents acting in a protective manner (vitamins, antioxidants, detoxifying enzyme-activating substances, etc.) [114]. Carcinogen metabolism affecting polymorphisms may modify probability of contact between carcinogens and target cells, thus acting at the stage of cancer initiation [65].

In hormone dependent tumors such as breast, prostate, ovarian and endometrial cancers, influences of polymorphisms of gene encoding factors involved in hormonal regulation are most strongly manifested. Polymorphisms in sex hormone receptor genes comprising those encoding estrogen receptors, progesterone receptor, and androgen receptor have been shown to be associated with cancer risk modulation [65]. Hormonal regulation can be influenced on interaction with dietary factors. Obesity has strongly impact on hormonal status. Apparently, some food components, such as phytoestrogens are known to be processed by the pathways similar as sex hormones [115].

There are various examples of the effects of diet on cancer risk. High consumption of red meat increase the risk of colorectal cancer [66]. N-Acetyl transferase (NAT) exists in two forms: NAT1 and NAT2, it is a phase II metabolism enzyme. Several polymorphisms exist in NAT1 and NAT2, some of them are capable of slow, intermediate, or fast acetylations. Heterocyclic Aromatic amines found in heated products like cooked red meat get through acetylation by NAT. On cooking of muscle meat at high temperature, some amino acids may react with creatinine to generate heterocyclic aromatic amines (HAA). Acetylation activates HAA to reactive metabolites which bind DNA and cause cancers. This acetylation can only be performed by NAT2 fast acetylators. People who consumed relatively large quantities of red meat with NAT fast acetylator genotype had a higher risk of developing colon cancer in them [66].

Specific dietary irritants, such as salts and preservatives have been suggested as being carcinogens for gastric cancer [116]. C667T polymorphism in MTHFR gene

which reduces enzymatic activity is inversely associated with occurrence of colorectal cancer. Less consumption of folate, vitamin B12, vitamin B6 or methionine in diet are associated with increased risk for cancer in CC or TT phenotype of MTHFR gene [117].

It has also been found that reactive oxygen species (ROS) such as superoxide anions, hydrogen peroxide, and hydroxyl radicals attack DNA bases, resulting in potential mistranscription of DNA sequence [118]. Such disruptions can interfere with DNA replication and thus produce mutations in oncogenes and tumor suppressor genes. ROS can also result in breakage of DNA strand, resulting in mutations or deletions of genetic material [119].

Dietary fibers have a protective effect against bowel cancer [120]. Growth of colonic tumors in both *in vitro* and *in vivo* systems gets inhibited on consumption of fish oil which is rich in omega-3 fatty acids [121–123].

Fruits and vegetables rich in bioactive components can prevent carcinogenesis by several mechanisms such as blocking metabolic activation through increasing detoxification. Detoxification enzymes as flavonoids, phenols, isothiocyanates, allyl sulfur compounds, indoles, and selenium can be modulated on consuming plant foods [124, 125].

Some of these bioactive components which may influence carcinogen metabolism, cell signaling, cell cycle control, apoptosis, hormonal balance and angiogenesis are calcium, zinc, selenium, folate, vitamins C, D and E, carotenoids, flavonoids, indoles, allyl sulfur compounds, conjugated linoleic acid and N-3 fatty acids [126]. Bioactive ingredients which play protective role in the cancer development are lycopene from tomatoes, resveratrol from grapes and berries, numeric acid from cinnamons, hesperidin from citrus fruits, carotenoids from red vegetables and fruits, ascorbic acid, coffee acid from coffee, types of soluble fibers, polyunsaturated and fatty acids from marine animals have [127]. Intake of proper diet with sufficient minerals and vitamins which are involved in regulatory and enzymatic processes reduces the risk of cancer. The deficiency of these micronutrients may lead to abnormalities. For example, zinc and folate is involved in DNA repairing process. Further natural compounds from plant source like apigenin (celery, parsley), curcumin (turmeric), epigallocatechin-3-gallate (green tea), resveratrol (red grape, peanuts, and berries), genistein (soybean), and allyl sulfur (garlic) have been reported to affect the cell cycle by different mechanisms. Some of these changes may be associated with the processing of synthesized proteins at the posttranslational level like shifts in the phosphorylation process of the main regulatory factors of cell division [128]. Tumor behavior can also be changed by other food ingredients through accelerated cell death and enhanced apoptosis. Apoptosis occur through two known pathways: the intrinsic, mitochondrial-mediated pathway; and the extrinsic, death receptor-mediated pathway [129].

Many of the studies by American Cancer Society [130] have shown the reduced risk of cancer associated with consumption of foods rich in vitamin C, such as fruits and vegetables. On contrary, evidence indicates that vitamin C supplements do not reduce cancer risk. From the above finding it can be said that, activity of fruits and vegetables in preventing cancer is due to consumption of many vitamins and other phytochemicals in a combination, not due to vitamin C alone.

### **5. Conclusion**

This chapter deals with the role of nutrigenomics for the prevention of noncommunicable diseases. The mother nature has made all humans almost genetically similar but, only 0.1% variation makes one individual unique from others with

**19**

**Author details**

**Conflict of interest**

Sananda Mondal\* and Debasish Panda

**Notes/thanks/other declarations**

functional individual nutrigenomics approach.

The authors declare no conflict of interest.

Sriniketan 731236, West Bengal, India

provided the original work is properly cited.

Department of Crop Physiology, Institute of Agriculture, Visva-Bharati,

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

We was thank full to editor for consideration of our chapter in IntechOpen Book.

\*Address all correspondence to: mondalsananda@gmail.com

*Nutrigenomics: An Interface of Gene-Diet-Disease Interaction*

respect to their phenotype and individual susceptibility to disease or health and also their differing response to nutrients. Interestingly, same diet can be a risk factor for some individuals whereas in others, it may prove beneficial. Besides, some diets may regulate genes to help in maintenance of health whereas, Some of them act as possible inducer of disease. Thus, based on knowledge of individual nutritional requirements, nutrition status and genotype; personalized nutrition & diet recommendations can be made to maintain the balance between health and disease to offer a healthy life. Major challenge is, in a populous country like ours, where people are still fighting for their basic needs, personalized nutrition system approach is a dream. Now, even the rural India is not spared from this menace of non communicable disease as it has also started embracing city culture, post era of globalization and urbanisation has brought significant changes in eating habits of rural India as well. At this moment, the most pertinent question is how to overcome this public health concern. The nutrigenomics approach is most effective and the only way out but on contrary it is not going to be so cheap to be available for masses. Also it is a very difficult task to handle the huge population with nutritional intervention as it will require adequate qualified professional along with advance lab facilities. For the time being as an alternative, public health awareness programme can play an important role in different way to protect the people from these diseases in broader sense. It shall basically focus on early identification of at-risk individuals and appropriate intervention in the form of weight reduction, changes in dietary habits and increased physical activity to help to prevent, or at least delay the onset of dietary disorders until India build itself capable in all respect to implement fully

*DOI: http://dx.doi.org/10.5772/intechopen.94602*

*Nutrigenomics: An Interface of Gene-Diet-Disease Interaction DOI: http://dx.doi.org/10.5772/intechopen.94602*

*Mineral Deficiencies - Electrolyte Disturbances, Genes, Diet and Disease Interface*

tions or deletions of genetic material [119].

fish oil which is rich in omega-3 fatty acids [121–123].

the extrinsic, death receptor-mediated pathway [129].

phytochemicals in a combination, not due to vitamin C alone.

gene [117].

foods [124, 125].

which reduces enzymatic activity is inversely associated with occurrence of colorectal cancer. Less consumption of folate, vitamin B12, vitamin B6 or methionine in diet are associated with increased risk for cancer in CC or TT phenotype of MTHFR

It has also been found that reactive oxygen species (ROS) such as superoxide anions, hydrogen peroxide, and hydroxyl radicals attack DNA bases, resulting in potential mistranscription of DNA sequence [118]. Such disruptions can interfere with DNA replication and thus produce mutations in oncogenes and tumor suppressor genes. ROS can also result in breakage of DNA strand, resulting in muta-

Dietary fibers have a protective effect against bowel cancer [120]. Growth of colonic tumors in both *in vitro* and *in vivo* systems gets inhibited on consumption of

Fruits and vegetables rich in bioactive components can prevent carcinogenesis by several mechanisms such as blocking metabolic activation through increasing detoxification. Detoxification enzymes as flavonoids, phenols, isothiocyanates, allyl sulfur compounds, indoles, and selenium can be modulated on consuming plant

Some of these bioactive components which may influence carcinogen metabolism, cell signaling, cell cycle control, apoptosis, hormonal balance and angiogenesis are calcium, zinc, selenium, folate, vitamins C, D and E, carotenoids, flavonoids, indoles, allyl sulfur compounds, conjugated linoleic acid and N-3 fatty acids [126]. Bioactive ingredients which play protective role in the cancer development are lycopene from tomatoes, resveratrol from grapes and berries, numeric acid from cinnamons, hesperidin from citrus fruits, carotenoids from red vegetables and fruits, ascorbic acid, coffee acid from coffee, types of soluble fibers, polyunsaturated and fatty acids from marine animals have [127]. Intake of proper diet with sufficient minerals and vitamins which are involved in regulatory and enzymatic processes reduces the risk of cancer. The deficiency of these micronutrients may lead to abnormalities. For example, zinc and folate is involved in DNA repairing process. Further natural compounds from plant source like apigenin (celery, parsley), curcumin (turmeric), epigallocatechin-3-gallate (green tea), resveratrol (red grape, peanuts, and berries), genistein (soybean), and allyl sulfur (garlic) have been reported to affect the cell cycle by different mechanisms. Some of these changes may be associated with the processing of synthesized proteins at the posttranslational level like shifts in the phosphorylation process of the main regulatory factors of cell division [128]. Tumor behavior can also be changed by other food ingredients through accelerated cell death and enhanced apoptosis. Apoptosis occur through two known pathways: the intrinsic, mitochondrial-mediated pathway; and

Many of the studies by American Cancer Society [130] have shown the reduced risk of cancer associated with consumption of foods rich in vitamin C, such as fruits and vegetables. On contrary, evidence indicates that vitamin C supplements do not reduce cancer risk. From the above finding it can be said that, activity of fruits and vegetables in preventing cancer is due to consumption of many vitamins and other

This chapter deals with the role of nutrigenomics for the prevention of noncommunicable diseases. The mother nature has made all humans almost genetically similar but, only 0.1% variation makes one individual unique from others with

**18**

**5. Conclusion**

respect to their phenotype and individual susceptibility to disease or health and also their differing response to nutrients. Interestingly, same diet can be a risk factor for some individuals whereas in others, it may prove beneficial. Besides, some diets may regulate genes to help in maintenance of health whereas, Some of them act as possible inducer of disease. Thus, based on knowledge of individual nutritional requirements, nutrition status and genotype; personalized nutrition & diet recommendations can be made to maintain the balance between health and disease to offer a healthy life. Major challenge is, in a populous country like ours, where people are still fighting for their basic needs, personalized nutrition system approach is a dream. Now, even the rural India is not spared from this menace of non communicable disease as it has also started embracing city culture, post era of globalization and urbanisation has brought significant changes in eating habits of rural India as well. At this moment, the most pertinent question is how to overcome this public health concern. The nutrigenomics approach is most effective and the only way out but on contrary it is not going to be so cheap to be available for masses. Also it is a very difficult task to handle the huge population with nutritional intervention as it will require adequate qualified professional along with advance lab facilities. For the time being as an alternative, public health awareness programme can play an important role in different way to protect the people from these diseases in broader sense. It shall basically focus on early identification of at-risk individuals and appropriate intervention in the form of weight reduction, changes in dietary habits and increased physical activity to help to prevent, or at least delay the onset of dietary disorders until India build itself capable in all respect to implement fully functional individual nutrigenomics approach.
