1. The association of 5-alpha reductase type 2 (SRD5A2) gene polymorphisms with prostate cancer in a Korean population
- Author
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Se Young Choi, Hae Jong Kim, Soon Chul Myung, and Hyun Sub Cheong
- Subjects
Biochemical recurrence ,Oncology ,Male ,Genomics/Stem Cells in Urology ,medicine.medical_specialty ,Genotype ,Population ,Single-nucleotide polymorphism ,Polymorphism, Single Nucleotide ,Prostate cancer ,3-Oxo-5-alpha-Steroid 4-Dehydrogenase ,Prostate ,Risk Factors ,Internal medicine ,Republic of Korea ,medicine ,Genetic predisposition ,Odds Ratio ,Humans ,Genetic Predisposition to Disease ,Testosterone ,education ,Aged ,Neoplasm Staging ,Genetics ,education.field_of_study ,Genetic polymorphism ,business.industry ,Membrane Proteins ,Prostatic Neoplasms ,Dihydrotestosterone ,Middle Aged ,Prostate-Specific Antigen ,medicine.disease ,Prostate-specific antigen ,medicine.anatomical_structure ,Logistic Models ,Haplotypes ,SRD5A2 ,Case-Control Studies ,Original Article ,Neoplasm Grading ,Human SRD5A2 protein ,business - Abstract
A single-nucleotide polymorphism (SNP) is a common DNA sequence variation in a population. Such variations can af fect susceptibilities and prognosis in various diseases. In terms of cancer, numerous efforts have been invested to identify the sources of genetic susceptibility. Through the outstanding studies of the International Human Genome Sequencing Project and the International HapMap Project, a large amount of data on genetic variations in the human genome has been accumulated, and this precious information has led to an explosion of investigations about SNPs. Prostate cancer is the most common malignancy in Western men, and the incidence of prostate cancer in Asian men is drastically increasing. More interestingly, prostate cancer shows not only a racial disparity but also a familial susceptibility in incidence, which suggests a strong influence of genetic factors. The biggest difference between prostate cancer and other malignancies is that androgens play a critical role in cancer progression from an early stage to castration-refractory prostate cancer. For this reason, numerous studies have f ocused on genetic polymorphisms of androgen and androgen receptor. Several studies have suggested that polymorphisms of repetitive CAG, GGC, and GGN repeats in the androgen receptor gene are associated with the incidence and mortality of prostate cancer, although this remains under debate [1,2,3]. In addition, genetic variations of cytochrome P450 (CYP17), which mediates activities essential for the production of sex steroids, have been reported to have borderline significant associations with the incidence of prostate cancer [4]. One important factor in the role of androgen in the prostate is 5-alpha-reductase (5-AR), which converts testosterone to dihydrotestosterone (DHT) in prostate cells. SRD5A1 and SRD5A2 encode 5-AR, and Lindstrom et al. [5] reported in a study based on 2,826 cancer cases and 1,705 controls that a polymorphism in SRD5A2 (rs623419) is associated with the risk of prostate cancer. Although this study recruited a relatively large number of cases and controls, the statistical significance was marginal, and the study did not include investigation of genetic influences on clinical or pathological outcomes. Audet-Walsh et al. [6] conducted a retrospective study in two independent cohorts composed of 526 white and 320 Asian men with localized prostate cancer, and four genetic variations (rs2208532, rs12470143, rs523349, and rs4952197 in SRD5A2) were associated with biochemical recurrence in both races. However, those investigators did not include clinical parameters such as Gleason score, prostate-specific antigen (PSA) level, or stage in their analysis. In this issue of the Journal, Choi et al. [7] report on the influence of genetic polymorphisms of SRD5A2 on prostate cancer risk and clinical outcomes in a Korean population. They selected 26 SNPs in the human SRD5A2 gene from international databases and investigated the correlations in 272 prostate cancer patients and 173 controls with benign prostatic hyperplasia. The data suggested that some SNPs and one haplotype were related to PSA levels, Gleason score, and clinical stage; however, SRD5A2 SNPs were not associated with susceptibility to prostate cancer. This study is highly informative because 26 SNPs were selected by use of comprehensive bioinformatics methods. Moreover, this case-control study included all available parameters for analysis. Advances in genotyping technologies have led to the feasibility of studying a large number of genetic polymorphisms, and the number of high-volume studies is rapidly increasing. However, we must keep in mind that the effects of genetic variation in incidence and prognosis of cancer are not outstanding and less than two folds. I believe that such genetic information should be combined with clinico-pathological variables to increase predictability, which could lead to a personalized risk classification for predicting the susceptibility and prognosis of prostate cancer.
- Published
- 2014