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INTRODUCTION:
Prostate cancer is a malignant tumor that consists of cells from the prostate gland. Generally, the tumor usually grows slowly and remains confined to the gland for many years. During this time, the tumor produces little or no symptoms or abnormalities.
IMPORTANCE OF PROSTATE CANCER:
Prostate cancer is the most common malignancy in American men and the second leading cause of deaths from cancer, after lung cancer. Estimated new cases and deaths from prostate cancer in the United States in 2010:
New cases: 217,730
Deaths: 32,050
POLYMORPHISMS:
CYP17 & SRD5A2:
Polymorphisms have been identified in 2 genes namely – 17-hydroxlase Cytochrome P450 gene & steroid 5-reductase type II gene. They are involved in Androgen biosynthesis & metabolism. The CYP17 A2 allele contains a T?C transition in the 5' promoter region that creates an additional Sp1-type (CCACC box) promoter site. The SRD5A2 valine to leucine (V89L) polymorphism has been correlated with lower dihydroxytestosterone levels.
VITAMIN D RECEPTOR:
Prostatic cells express vitamin D receptor, which mediates the functions of 1,25-dihydroxyvitamin D. strong inverse associations between the VDR polymorphisms, TaqI, poly(A), & BsmI and risk of prostate cancer have been reported.
P53 CODON 72 & p21 CODON 31:
The tumor suppressor gene p53 and its downstream effector p21 play major roles in the development of human malignancy. Polymorphic variants of p53 at codon 72, and p21 at codon 31, have been found to be associated with prostate cancer.
HUMAN SRD5A2 GENE:
Elevated dihydrotestosterone levels have been suggested to increase the risk of prostate cancer. The human SRD5A2 gene encodes the type II steroid 5a-reductase, which converts testosterone to the more bioactive compound dihydrotestosterone.
ESTROGEN RECEPTOR-BETA GENE:
Variation in genes involved in the estrogen pathway has been reported. There are association of SNPs in the estrogen receptor-beta (ER-beta) gene and prostate cancer. One SNP in the promoter region of ER-beta, rs2987983, was associated with an overall prostate cancer risk of 1.23 and 1.35 for localized disease.
APOPTOTIC GENES:
An association between genetic variants in apoptotic genes and prostate cancer risk has been proposed. The BCL-2 gene has antiapoptotic functions. 70% decrease in prostate cancer risk in European Americans with the -938AA genotype in the BCL-2 gene and an approximate 60% decrease in risk in Jamaican men of African descent with the 21G allele has been reported.
OTHER GENES INVOLVED:
Molecular epidemiology studies of prostate cancer have also examined associations with vitamin D receptor genes and with SNP variants in phase I and phase II genes such as CYP1A1, CYP2D6,CYP17A2, CYP3A4, GST, NAT1, and NAT2. A large meta-analysis studyingGSTM1, GSTT1, and GSTP1 found a modest association between prostate cancer susceptibility andGSTM1.
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