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Review
. 2012 Jul;33(7):1259-69.
doi: 10.1093/carcin/bgs150. Epub 2012 Apr 20.

Gene variants in the angiogenesis pathway and prostate cancer

Ernest K Amankwah  1 , Thomas A Sellers, Jong Y Park
Affiliations
Review

Gene variants in the angiogenesis pathway and prostate cancer

Ernest K Amankwah et al. Carcinogenesis. 2012 Jul.

Abstract

Although the causes of prostate cancer are still unknown, numerous studies support the role of genetic factors in the development and progression of this disease. Single nucleotide polymorphisms (SNPs) in key angiogenesis genes have been studied in prostate cancer. In this review, we provide an overview of the current knowledge of the role of genetic variants in the angiogenesis pathway in prostate cancer risk and progression. Of the 17 prostate cancer genome-wide association studies (GWAS) conducted to date, only one identified disease-associated SNPs in a region of an angiogenesis pathway gene. An association was observed between aggressive disease and three intergenic SNPs (rs11199874, rs10749408 and rs10788165) in a region on chromosome 10q26 that encompasses FGFR2. The majority (27/32, 84.4%) of primary candidate gene studies reviewed had a small (n < 800, 20/32, 62.5%) to medium sample size (n = 800-2000, 7/32, 21.9%), whereas only five (15.6%) had a large sample size (n ≥ 2000). Results from the large studies revealed associations with risk and aggressive disease for SNPs in NOS2A, NOS3 and MMP-2 and risk for HIF1-α. Meta-analyses have so far been conducted on FGFR2, TGF-β, TNF-α, HIF1-α and IL10 and the results reveal an association with risk for SNPs in FGFR2 and TGF-β and aggressive disease for SNPs in IL-10. Thus, existing evidence from GWAS and large candidate gene studies indicates that SNPs from a limited number of angiogenesis pathway genes are associated with prostate cancer risk and progression.

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Figures

Fig. 1.
Fig. 1.
The role of angiogenesis in tumor progression. Post-natal angiogenesis is regulated by a balanced and continuous interplay of factors that act as pro-angiogenic (VEGFs, FGF, EGF, HIF, TGF-β and TNF-α), anti-angiogenic (endostatin and IFN) or both pro-/anti-angiogenic (MMPs and ILs). However, a growing tumor can tilt the balance toward pro-angiogenic factors to promote vascular growth and facilitate tumor invasion, regional lymph node and distant metastasis.
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