**1. Introduction**

106 Cancer Prevention – From Mechanisms to Translational Benefits

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The term cancer is used generically to represent a set of more than 100 diseases, including malignant tumors from different locations. The understanding, diagnosis and management of malignancies require scientific knowledge and experiences ranging from the knowledge of the complex epigenetic mechanisms (intracellular regulation) to the individual lifestyle choice in different societies. Therefore, cancer prevention, prognosis and control are issues of profound importance to global public health.

Cancer appears as a major public health problem both in developed and developing countries. According to the latest report from the International Agency for Research on Cancer (IARC) / WHO (Boyle & Levin, 2008), the overall impact of cancer more than doubled in 30 years. About 12 million cancer cases and 7 million cancer deaths are estimated to have occurred in 2008. Of these, lung cancer had the greatest incidence rate (1.52 million new cases), followed by breast cancer (1.29 million cases) and colorectal cancer (1.15 million cases). Due to poor prognosis, lung cancer was the leading cause of death (1.31 million), followed by stomach cancer (780,000 deaths) and liver cancer (699,000 deaths About one million new cancer cases and 589,000 cancer deaths are estimated to have occurred in South America, Central America and in the Caribbean. Prostate cancer was the most common cancer in men, followed by lung, stomach and colon and rectum. Breast cancer was the most common cancer in women, followed by cancers of the cervix, colon and rectum, stomach and lung (Boyle & Levin, 2008).

The continued population growth and ageing significantly affect the impact of cancer in the world, which is greater in developing and under-developed countries. Half of the world's new cancer cases and about two thirds of cancer deaths are estimated to have occurred in 2008 in these countries (Farmer et al., 2010). Therefore, it is essential that resources and efforts are directed towards guiding strategies for cancer prevention, diagnosis and treatment.

In this particular chapter the strategies for prevention, diagnosis and treatment in the current epigenetic scenario of the new molecular mechanisms proposed for the development of cancer will be discussed.

Kaiso and Prognosis of Cancer in the Current Epigenetic Paradigm 109

embryonic stem cells were used to confirm the origin of the tumor clone and test the initial conservation of the tumorigenic capacity of these cells originated by tumor cores. In these experiments it has been unequivocally demonstrated that the clones derived from cancer cells and that the nuclei of cancer cells (leukemia, lymphoma and breast cancer) were able to sustain the embryonic development until the preimplantation blastocyst stage. It has also been demonstrated that the oocyte cytoplasm is able to reprogram the epigenetic state of some nuclei of tumor cells, transforming these cells into pluripotent and also enabling them to sustain the differentiation of multiple somatic cell types such as melanocytes, lymphocytes and fibloblasts. Therefore, the cancer state is an epigenetic cell state susceptible

The role of epigenetics was also confirmed by studying cohorts of twins and analyzing the concordance in cancer between monozygotic and dizygotic twins, and, thus, providing information about whether family patterns are influenced by environmental or genetic patterns. If the concordance in cancer is greater between monozygotic twins (who share 100% of the genes) than between dizygotic twins (who share in average 50% of the segregated genes) the genetic effects are probably more important. On the other hand, if the concordance rate is similar in both types of twins, then the environmental effects are probably more important. Thus, the use of statistics to analyze large populations of twins allows us to estimate the magnitude of environmental and genetic effects on susceptibility to

This retrospective study has shown that hereditary factors make a minor contribution to susceptibility to most types of neoplasms, indicating that the environment plays a major role in sporadic cancer in populations living in the study areas (Lichtenstein et al., 2000). The study, on the other hand, stresses that some types of cancer, such as prostate and colorectal

Thus, even more important aspects related to diseases are being reworked, and cancer may no longer be categorized as a disease based on genetics alone, and all the data indicate that most commonly diagnosed cancers in the world have primarily environmental or epigenetic origin. Except for some types of cancer considered hereditary, familial adenomatous polyposis, colorectal cancer and prostate cancer, the contribution of hereditary factors to the

The DNA methylation takes place only at cytosine bases that are located 5' to a guanosine in a CpG dinucleotide. This dinucleotide is actually underrepresented in the genome, but short regions, known as CpG islands, are rich in CpG content. Most CpG islands are found in the proximal promoter regions of almost half of the genes in the mammalian genome and are, generally, unmethylated in normal cells. In cancer, however, the hypermethylation of these promoter regions is now the most well categorized epigenetic change to occur in tumours, it is found in virtually every type of human neoplasm and is associated with the inappropriate

These tumour suppressor genes are predicted to be important for tumorigenesis, but seem not to be frequently mutated and *de novo* hypermethylation of CpG islands in the promoters of *MLH1* (mutL homologue 1, colon cancer, non-polyposis type 2) (Herman et al., 1998) and

cancers are more influenced by genetic factors than previously thought.

transcriptional silencing of genes, involving tumour-suppressor genes.

development of cancer is thought to be relatively small.

**5. How the epigenetics affects genetics** 

of change regardless of the DNA alterations (Feinberg, 2008).

sporadic cancer.
