Systematic replication study of reported genetic associations in prostate cancer: Strong support for genetic variation in the androgen pathwayShow others and affiliations
2006 (English)In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 66, no 16, p. 1729-1743Article, review/survey (Refereed) Published
Abstract [en]
BACKGROUND. Association studies have become a common and popular method to identify genetic variants predisposing to complex diseases. Despite considerable efforts and initial promising findings, the field of prostate cancer genetics is characterized by inconclusive reports and no prostate cancer gene has yet been established. METHODS. We performed a literature review and identified 79 different polymorphisms reported to influence prostate cancer risk. Of these, 46 were selected and tested for association in a large Swedish population-based case-control prostate cancer population. RESULTS. We observed significant (P < 0.05) confirmation for six polymorphisms located in five different genes. Three of them coded for key enzymes in the androgen biosynthesis and response pathway; the CAG repeat in the androgen receptor (AR) gene (P = 0.03), one SNP in the CYP17 gene (P = 0.04), two SNPs in the SRD5A2 gene (P = 0.02 and 0.02, respectively), a deletion of the GSTT1. gene (P = 0.006), and one SNP in the MSR1 gene, IVS5-59C > A, (P = 0.009). CONCLUSIONS. Notwithstanding the difficulties to replicate findings in genetic association studies, our results strongly support the importance of androgen pathway genes in prostate cancer etiology.
Place, publisher, year, edition, pages
Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. Umea Univ, Dept Radiat Sci Oncol, Umea, Sweden. Wake Forest Univ, Sch Med, Ctr Human Genome, Winston Salem, NC USA. Karolinska Inst, Ctr Genome & Bioinformat, Stockholm, Sweden. Univ Leicester, Dept Genet, Leicester, Leics, England. Johns Hopkins Med Inst, Dept Urol, Baltimore, MD USA. Karolinska Inst, CLINTEC, Ctr Oncol, Stockholm, Sweden.: WILEY-LISS , 2006. Vol. 66, no 16, p. 1729-1743
Keywords [en]
prostate cancer, association, polymorphism, replication, androgen pathway
National Category
Health Sciences
Identifiers
URN: urn:nbn:se:mdh:diva-40715DOI: 10.1002/pros.20489ISI: 000242459900005PubMedID: 16998812Scopus ID: 2-s2.0-33845287059OAI: oai:DiVA.org:mdh-40715DiVA, id: diva2:1246065
2018-09-062018-09-062022-03-18Bibliographically approved