Replication of Prostate Cancer Risk Variants in a Danish Case-Control Association Study

• 作者: Anders B?rglum Diem Nguyen Bentzon Karina Dalsgaard S?rensen Mette Nyegaard Michael Borre Torben ?rntoft
• 来源期刊: 泌尿学期刊(英文)
• 学科: 医学
• 关键词: SNP Family History CUMULATIVE Effect Biochemical RELAPSE PROSTATE Cancer Risk
• 年，卷（期）: 2012,（2）
• 页码范围: 45-54
• 页数: 10页
• 分类号: R73

摘要

Background: Prostate cancer is one of the main causes for cancer morbidity and mortality in Western countries. Recently, several single nucleotide polymorphisms (SNPs) associated with prostate cancer have been identified in genome-wide association studies and multiple variant models have been developed to predict prostate cancer risk. The association between genetic markers and clinico-pathological tumor variables has, however, been inconsistent. Methods and Materials: A total of 32 previously identified prostate cancer-associated risk SNPs were genotyped in 648 prostate cancer cases and 526 age-matched controls. Family history was obtained by questionnaire. Age at diagnosis, clinical tumor variables including pre- and postoperative PSA, Gleason score, and T stage were obtained from prospectively collected clinical data (Aarhus Prostate Cancer Study). The SNPs were genotyped using Sequenom and Taqman assays and associations between SNPs, prostate cancer risk, and clinico-pathological variables were assessed. Results: Seventeen SNPs were successfully replicated in our case-control study and the association estimates were consistent with previous reports. Four markers were excluded from further analysis due to linkage disequilibrium. The cumulative effect of having the disease-associated genotype at five SNPs (rs4430796, rs6983267, rs1859962, rs1447295 and rs16901979) increased the prostate cancer risk with odds ratio 6.02 (95% CI: 2.21 - 16.38;P = 1.0 × 10–4) in patients with any combination of ≥4 markers compared with patients without any of the five SNPs (P for trend = 1.0 × 10–4). Six markers were significantly associated with clinico-pathological variables: SNP rs2735839 (GG) at locus 19q13, which is in the KLK3 gene encoding PSA, was associated with high preoperative PSA (P = 0.04), low Gleason score (P = 0.01) and low T stage (P = 0.02). Variants rs5759167 (GG/GT) (22q13) and rs7679673 (CC/CA) (4q24) were correlated with low risk for biochemical relapse (P = 0.015 and P = 0.009, respectively), wherea