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Prostate Cancer: Risk of Cancer With Altered Genes

BY: Chandra Kala | Category: Healthcare | Submitted: 2012-11-20 04:58:03
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Article Summary: "Prostate is a part of the male reproductive present in the males of mammals. Prostate Cancer is the most common form of cancer occurring in the older males in Developed countries. Future treatment for prostate cancer should be based on genetic background on the genes involved in response and resistance to drugs or hormones whic.."

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Prostate is an exocrine gland present in the males of mammals. It is a part of the male reproductive system and secretes whitish milky acidic fluid which makes two third volume of the semen. Prostate helps in semen ejaculation as it contains smooth muscles. Uncontrolled cell growth in the prostate gland results in Prostate Cancer. Prostate Cancer is the most common form of cancer occurring in the older males in Developed countries. The development of cancer in prostate gland is very slow and detection in the early stages is difficult. In the final stages of prostate cancer, the cells spreads (metastasis) to other organs of the body and might results in death of the individuals.

The symptoms of prostate cancer may vary from individual to individuals. It may cause pain and difficulty during urination among some patients, while some doesn't have any symptoms. Environmental factors, genetic factors, food, and other factors play a role in development of prostate cancer. Familial history is one of the major factors in the development of prostate cancer. The risk of prostate cancer is nearly doubled when a person's immediate male relative like father or brother has prostate cancer. Dietary factors are also linked with prostate cancer development. Lower levels of vitamin D in the blood increases the risk of prostate cancer. Similarly, higher meat intake has also been associated with high risk of development of prostate cancer.

The treatment for prostate cancer includes surgery, radiation therapy or hormone therapy (androgen -deprivation therapy) based on the stage and condition of cancer tissue. The prostate cancer growth depends initially on androgen and androgen deprivation therapy reduces the levels of dihydrotestosterone (DHT) and testosterone, thereby restricting the tumor cell proliferation and inducing apoptosis. The androgen deprivation therapy is a temporary relief and patients who are sensitive to androgen deprivation therapy are reported with disease progression in two to three years leading to situation called Castration Resistance Prostate Cancer (CRPC). CRPC is a critical stage of prostate cancer where the tumor develops even in low concentration of androgen and Castration has no role in further development of prostate cancer.

Mutations in the several genes are found associated with prostate cancer. No single gene in particular is linked with development of prostate cancer. Genomic alterations such as insertion of nucleotides in the both arms of chromosome 7, q arm of chromosome 8, and X and deletion of nucleotides in the p arm of chromosome 8, and q arms of chromosomes 10, 13, and 16 have been reported in prostate cancer patients. Chromosomal translocations in the ETS family of transcription factors and TMPRSS2 are present in samples of prostate cancer tissue. Gene mutations are also found in many genes including NKX3.1, c-MYC, PTEN, AR, BRCA1, BRCA1, HPC1, TP53, VDR, PTEN, CD44, KAI1, CDH1, and p27. Fused genes due to chromosomal translocations are also observed involving TMPRSS2 gene with ETS family transcription factors. Androgen receptor pathway activation and transcription of androgen regulated genes are observed due to cross talk of between growth factor pathways such as EGF, IGF etc. Over expression of ERBB2 in prostate cancer leads to constitutive activation of Androgen pathway and ERBB receptor pathway that may be important in AR-dependent and AR-independent prostate cancer growth and survival.

Single Nucleotide Polymorphisms (SNPs) of few genes are associated with prostate cancer risk. CYP17 gene SNP rs743572 is significantly associated with increased risk in African population than in Caucasian and Asian populations. Apart from genomic alteration, epigenetic variations are also observed in many genes in prostate cancer tissue. Hypermethylation in the CpG islands present in the promoter sequence of detoxifying gene GSTP is an important event, which makes the cells more prone for additional mutations. Hypermethylation is also observed in the promoters of CDH1 (E-cadherin) gene.

Prostate Cancer diagnosis is the main area of research where more research is being carried involving non-invasive methods. Detection of certain antibodies or gene products in blood or urine will help in early detection of prostate cancer. Occurrence of EN2 gene products in the urine has been associated with high probability of developing prostate cancer. Presence of PCA3 mRNA expression in higher quantity is directly associated with positive prostate cancer tissues in patients. Presence of EPCA-2 (early prostate cancer antigen-2) in blood may correlate with presence of prostate cancer.

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