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Gene & Protein in Disease Natural carotenoids prevent prostate cancer

1.4 million newly reported cases and 375,000 recorded the subsequent subsections. Ethnicity is another significant
deaths. Histologically, PCa arises from luminal epithelial factor, with men of Black African ancestry experiencing a
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cells characterized by heightened expression of androgen higher incidence, greater severity, and increased mortality
receptors (ARs) and differentiation antigens, including rates in relation to PCa. Various factors, including
cytokeratin 8 and prostate-specific antigen. Basal cells, smoking, alcohol consumption, obesity, physical exercise,
marked by a lower intensity in the expression of ARs, diet, medications, and sex hormone-related factors, can
and sporadic neuroendocrine cells also play roles. The influence the risk and progression of PCa. 6
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development of prostate adenocarcinoma is attributed
to the inactivation of tumor suppressor genes such as 1.2.1. Genetic mechanisms
SMAD4, PTEN, and TRP53, which can occur either in Translocations involving transcription factors of the E26
both luminal and basal cells or independently in each transformation-specific (ETS) family, such as ERG genes,
cell type. It remains unclear if neuroendocrine cells found and androgen-regulated promoters appear to be the most
in the stratum basale (also known as basal layer) play a role frequent genomic alterations in prostate carcinoma. The
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in prostate neoplasia. The transformation of cells derived activation of ETS contributes to carcinogenesis through
from normal human prostate epithelial tissue into malignant diverse mechanisms, encompassing lineage specification,
cells results in the development of prostate adenocarcinoma, epigenetic modifications, genome instability, and remodeling
squamous carcinoma, or neuroendocrine carcinoma, of metabolism. In addition, the amplification of the MYC
with metastatic PCa being the primary contributor to gene enhances the progression of PCa by activating
mortality. Metastases commonly occur in bones, lungs, and protumorigenic factors pivotal for cell growth and
liver. Epidemiologically, PCa displays heterogeneity, with development through transcription. AR signaling plays a
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occurrence rates ranging from 6.3 to 83.4/100,000 individuals central role in prostate function and maturation. Thus, any
globally. Regions such as Southern Africa, Australia, the mutation or amplification of AR causes the development
Caribbean, North America, and Western and Northern of PCa. Furthermore, PTEN functions to inhibit the
Europe exhibit the highest percentages of prostate PI3K–AKT–mammalian target of the rapamycin (mTOR)
malignancy, while North Africa and Asia exhibit the lowest pathway, thereby regulating cell survival, proliferation, and
rates. Mortality rates show notable variations compared to metabolic processes related to energy production. The loss
incidence rates, with the Caribbean recording the highest of PTEN, often due to deletion and mutation, is estimated
rates at 75.8/100,000 people, followed by sub-Saharan to occur in 40% of prostate neoplasia cases.
Africa at 22.0/100,000 people, and Micronesia/Polynesia at In addition, SMAD4 serves as a tumor suppressor,
18.8/100,000 people. Furthermore, it is widely acknowledged exerting influence on downstream activity in the
and documented that men of African ancestry have a higher TGFβ pathway. It plays a vital role in regulating gene
predisposition to develop PCa during their lifetime, while transcription, suppressing epithelial cell growth, and
men of Asian descent appear to be less susceptible. 6
reshaping the tumor microenvironment (TME). TME
1.2. Etiology of PCa refers to the normal cells and elements existing within the
tumor, encompassing substances generated and released
The onset of PCa is influenced by a multitude of factors, by them. Continuous interactions between cancerous cells
both modifiable and unmodifiable, contributing to its and the microenvironment surrounding the tumor are
multifactorial etiology. Particularly, factors contributing to crucial in the initiation, advancement, spread, and reaction
susceptibility to PCa include aging, family history, genetic to treatments of the tumor. 7
predisposition, and ethnicity. As far as age is concerned,
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PCa is infrequent before the age of 40, with the average BRCA genes are pivotal in transcription and DNA
age at diagnosis being 66 in North America. It is worth repair processes related to double-stranded breaks and
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noting that the occurrence of prostate neoplasia rises with recombination. Mutations in the germline of BRCA genes
age, a pattern observed in both developed and developing are linked to a heightened risk of PCa or a more invasive
countries. For men aged 38 and below, the likelihood phenotype, resulting in a poorer prognosis. Finally, SPOP
of acquiring PCa is 0.005%. In addition, PCa exhibits is a constituent of a BTB–CUL3–RBX1 E3 ubiquitin–
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heightened heritability, with men having a two- to four- protein ligase complex. Mutations in SPOP lead to the
fold increased risk of developing the disease if their father maintenance of tumorigenic molecules, including JNK,
or brother has been diagnosed with it. Studies have also NCOA3, DEK, and BET family proteins. 5
demonstrated that families with traits of both familial
breast cancer and familial PCa have an elevated risk of 1.2.2. Epigenetic mechanisms
developing PCa. Family history involves a combination of Epigenetics is involved in both the initiation and
genetic and epigenetic factors, which will be explored in development of PCa. During tumor development, epigenetic

Volume 3 Issue 1 (2024) 2 https://doi.org/10.36922/gpd.2827