Systematic replication study of reported genetic associations in prostate cancer: Strong support for genetic variation in the androgen pathway

Sara Lindström, S. Lilly Zheng, Fredrik Wiklund, Björn Anders Jonsson, Hans Olov Adami, Katarina Augustsson Bälter, Anthony J. Brookes, Jielin Sun, Bao Li Chang, Wennuan Liu, Ge Li, William B. Isaacs, Jan Adolfsson, Henrik Grönberg, Jianfeng Xu

Research output: Contribution to journalReview article

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1729-1743
Number of pages15
JournalProstate
Volume66
Issue number16
DOIs
StatePublished - Dec 1 2006

Keywords

  • Androgen pathway
  • Association
  • Polymorphism
  • Prostate cancer
  • Replication

ASJC Scopus subject areas

  • Oncology
  • Urology

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    Lindström, S., Zheng, S. L., Wiklund, F., Jonsson, B. A., Adami, H. O., Bälter, K. A., Brookes, A. J., Sun, J., Chang, B. L., Liu, W., Li, G., Isaacs, W. B., Adolfsson, J., Grönberg, H., & Xu, J. (2006). Systematic replication study of reported genetic associations in prostate cancer: Strong support for genetic variation in the androgen pathway. Prostate, 66(16), 1729-1743. https://doi.org/10.1002/pros.20489