Prostate cancer susceptibility variants confer increased risk of disease progression.

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
Iona ChengJohn S Witte

Abstract

Genome-wide association studies have identified numerous single nucleotide polymorphisms (SNP) associated with the risk of prostate cancer. Our objective was to determine whether these SNPs affect the progression of prostate cancer. We genotyped 26 SNPs previously associated with prostate cancer risk among 788 aggressive prostate cancer patients who were treated by radical prostatectomy or radiation therapy. Prostate cancer progression was defined as biochemical recurrence based on posttreatment prostate-specific antigen levels of >0.3 ng/mL for radical prostatectomy patients or a 2-ng/mL increase above the nadir for radiation therapy patients, initiation of hormone treatment, or metastases. We assessed the association between independent and combined SNPs and disease progression by Cox proportional hazards regression. Five SNPs showed independent associations with prostate cancer progression (rs12621278, rs629242, rs9364554, rs4430796, and rs5945572) based on stepwise regression analysis. The strongest SNP was rs12621278 in the ITGA6 locus, which was associated with a 2.4-fold increased risk of progression (P = 0.0003). When considering the sum of risk alleles across these five SNPs, each additional allele was associated with ...Continue Reading

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