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Polymorphisms in Angiogenesis-Related Genes and Prostate Cancer

¹ Department of Epidemiology and Surveillance Research, American Cancer Society, Atlanta, Georgia; ² Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland; ³ Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania; and ⁴ Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina

Requests for reprints: Eric J. Jacobs, Epidemiology and Surveillance Research, American Cancer Society, National Home Office, 250 Williams Street, Atlanta, GA 30303-1002. Phone: 404-329-7916; Fax: 404-327-6450. E-mail: Eric.Jacobs{at}cancer.org

Background: Angiogenesis is required for development and progression of prostate cancer. Potentially functional single nucleotide polymorphisms (SNP) in genes important in prostate angiogenesis (VEGF, HIF1A, and NOS3) have previously been associated with risk or severity of prostate cancer.

Methods: Prostate cancer cases (n = 1,425) and controls (n = 1,453) were selected from the Cancer Prevention Study II Nutrition Cohort. We examined associations between 58 SNPs in nine angiogenesis-related candidate genes (EGF, LTA, HIF1A, HIF1AN, MMP2, MMP9, NOS2A, NOS3, VEGF) and risk of overall and advanced prostate cancer. Unconditional logistic regression was used to estimate odds ratios, adjusted for matching factors.

Results: Our results did not replicate previously observed associations with SNPs in VEGF, HIF1A, or NOS3, nor did we observe associations with SNPs in EGF, LTA, HIF1AN, MMP9, or NOS2A. In the MMP2 gene, three intronic SNPs, all in linkage disequilibrium, were associated with overall and advanced prostate cancer (for overall prostate cancer, P_trend = 0.01 for rs1477017, P_trend = 0.01 for rs17301608, P_trend = 0.02 for rs11639960). However, two of these SNPs (rs17301608 and rs11639960) were examined and were not associated with prostate cancer in a recent genome-wide association study using prostate cancer cases and controls from the Prostate, Lung, Colorectal, and Ovary study cohort. Furthermore, when we pooled our results for these two SNPs with those from the Prostate, Lung, Colorectal, and Ovary cohort; neither SNP was associated with prostate cancer.

Conclusion: None of the SNPs examined seem likely to be importantly associated with risk of overall or advanced prostate cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(4):972–7)