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Gene & Protein in Disease Natural carotenoids prevent prostate cancer

alterations in different genes and pathways, as well as prostate atrophy. Estrogens can initiate tumor growth as
modifications in methylation patterns, are observed. The chemical carcinogens by activating metabolic pathways.
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glutathione-S-transferase P1 (GSTP1) gene has been Patients prescribed 5-alpha reductase inhibitors for
implicated in prostate neoplasia, encoding an enzyme benign prostatic hyperplasia may face an increased risk of
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responsible for DNA protection against various factors, high-grade carcinogenesis. However, other studies have
including carcinogens, and participating in the catalytic suggested that the impact of 5-alpha reductase inhibitors
cycle of PRDX6, an important antioxidant enzym. In prostate on the risk of PCa is lower in Asian populations. In
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tumorigenesis, the GSTP1 gene is not expressed in cancer addition to androgens and estrogens, insulin-like growth
cells since its promoter is methylated. The promoter region factor 1 (IGF-1), also known as somatomedin C, has an
of GSTP1 undergoes hypermethylation in around 75% of pre- important impact on prostatic cancer. Numerous studies
invasive high-grade prostatic cancer and over 90% of prostate have investigated the correlation between elevated levels of
tumors. Hypermethylation also occurs at promoters of other IGF-1 and the risk of PCa. 16
genes involved in PCa, including adenomatous polyposis
coli, Ras-associated domain family 1A, O6-methylguanine 1.3.2. Family history
DNA methyltransferase, and others. In addition to DNA The association between family history and the incidence
methylation, chromatin acetylation and/or histone of PCa is well documented. Patients with this neoplasia
modifications are also epigenetic alterations. In prostate can inherit the disease from relatives, and studies have
carcinoma, the transcription process of AR effector genes is established that a history of breast cancer in the family
regulated by a cluster of transcription factors. Particularly, can also increase the likelihood of prostate carcinogenesis.
histone acetylation leads to the active transcription of target Consequently, men with a family history of PCa should
genes, as AR agonists conscript the AR and coactivators with undergo more frequent screening. The risk of PCa is
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histone acetyltransferase activity to the promoter of AR genes. influenced by factors such as the age of the relative at cancer
On the contrary, gene expression is blocked by the connection detection and mortality, as well as the degree of family
of histone deacetylases with corepressors such as SMRT or correlation. Numerous studies have indicated that having
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NCoR, which are activated by AR antagonists. 5,9 a first-degree relative diagnosed with PCa may increase the
risk by an estimated factor of 2.5. In addition, several studies
1.3. Risk factors assessing the age of relatives have found that younger men
A variety of risk factors plays a crucial role in PCa tumor under 65 years of age in the family have a risk estimate of
growth. PCa is a multifactorial disease, with numerous 4.3. Hemminki and Czene’s studies have highlighted the
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exogenous risk factors such as physical activity, diet, significance of the father’s age at diagnosis, with an estimated
obesity, smoking, alcohol and environmental agents, and risk of 3.55 for sons if the father was diagnosed before the age
endogenous risk factors such as hormones, family history, of 60, compared to a risk of 2.5 if the father was diagnosed
race, and aging. While factors such as age and ethnicity are after 60 years of age. Similarly, having an affected brother
unalterable, others such as diet can be modified. 10 under the age of 55 is associated with a higher estimated
risk of 8.05, whereas the risk decreases to 3.5 after the age of
1.3.1. Hormones 55 years. In families where both the father and brother have
Recent studies have pointed out the complexity of the been diagnosed with PCa, the risk for another son may be
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interaction between a wide range of hormones such as as high as 33.09 before the age of 55 years. Moreover, PCa
testosterone, free testosterone, sex hormone-binding has been associated with familial cancer syndromes, such
globulin (SHBG), 5-alpha reductase, and estrogens, making as hereditary breast and ovarian cancer syndrome (HBOC)
it difficult to determine the hormones’ precise role in prostate and Lynch syndrome (LS). HBOC syndrome, characterized
carcinogenesis. While multiple studies have reported by mutations in BRCA1 and BRCA2 genes, is associated
elevated testosterone levels in cancerous tissue, these levels with multiple incidences of breast, ovarian, and pancreatic
have not consistently correlated with aggressive disease. 11-13 cancer in relatives. Studies suggest that men with hereditary
Mendelian randomization (MR) analysis has suggested a mutations in BRCA1 and BRCA2 have a higher incidence
correlation between high levels of free testosterone and an and mortality rate for PCa. LS, involving mutations in the
increased risk of aggressive PCa, although this association DNA mismatch repair system, increases the likelihood of
was not consistently observed in blood sample analyses. PCa by threefold in affected men. 20
SHBG levels were not found to be associated with an
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elevated risk. In addition, high concentrations of estrogens, 1.3.3. Race
whether from maternal exposure or pharmaceutical doses, The incidence of PCa varies by geographic area.
have been implicated in stimulating tumorigenesis through GLOBOCAN data indicate that the highest incidence is

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