Wang Liang, McDonnell Shannon K, Slusser Joshua P, Hebbring Scott J, Cunningham Julie M, Jacobsen Steven J, Cerhan James R, Blute Michael L, Schaid Daniel J, Thibodeau Stephen N
Departments of Laboratory Medicine and Pathology, Health Sciences Research, and Urology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Cancer Res. 2007 Apr 1;67(7):2944-50. doi: 10.1158/0008-5472.CAN-06-3186.
Two variants (rs1447295/DG8S737) of chromosome 8q24 were recently reported to be associated with increased risk of prostate cancer (PC). To confirm this finding, we genotyped and compared the frequencies of these polymorphisms among 1,121 Caucasian men with PC (435 men with familial PC, 491 men with sporadic PC, and 195 men with aggressive PC) to 545 population-based controls. For the single nucleotide polymorphism marker rs1447295, frequencies of the minor allele (A) were 10.3% in controls, 11.9% in sporadic cases, 16.7% in familial cases, and 17.2% in aggressive cases. Compared with controls, the A allele was significantly more common in both familial PC [odds ratios (OR), 1.93; 95% confidence intervals (95% CI), 1.37-2.72; P = 0.0004] and aggressive PC (OR, 1.87; 95% CI, 1.28-2.74; P = 0.0005) but not for sporadic PC (OR, 1.16; 95% CI, 0.85-1.58; P = 0.25). Although the A allele was more frequent in aggressive PC cases when compared with controls, the allele frequencies were similar among cases with high- and low-grade PC (Gleason grades <7 and >/=7, respectively). For the microsatellite marker DG8S737, the -8 allele was significantly more frequent in familial PC (OR, 1.68; 95% CI, 1.09-2.60; P = 0.031), whereas the -10 allele was more frequent in aggressive PC (OR, 2.85; 95% CI, 1.52-5.36; P = 0.0004). Haplotype analysis showed significant differences in haplotype frequencies between the familial PC (P = 0.006) and aggressive PC (P = 0.005) cases versus controls. The -8/A haplotype showed the strongest association with familial PC (P = 0.008), whereas the -10/A haplotype was most strongly associated with aggressive PC (P = 0.00005). These results further confirm the importance of these two polymorphic variants (rs1447295 and DG8S737) as risk factors for PC. However, the mechanism explaining this increased risk has not yet been established.
最近有报道称，8号染色体q24区域的两个变异体（rs1447295/DG8S737）与前列腺癌（PC）风险增加有关。为证实这一发现，我们对1121名患有PC的白种男性（435名家族性PC患者、491名散发性PC患者和195名侵袭性PC患者）以及545名基于人群的对照者进行了基因分型，并比较了这些多态性的频率。对于单核苷酸多态性标记rs1447295，对照者中次要等位基因（A）的频率为10.3%，散发性病例中为11.9%，家族性病例中为16.7%，侵袭性病例中为17.2%。与对照者相比，A等位基因在家族性PC [优势比（OR），1.93；95%置信区间（95%CI），1.37 - 2.72；P = 0.0004]和侵袭性PC（OR，1.87；95%CI，1.28 - 2.74；P = 0.0005）中显著更常见，但在散发性PC中并非如此（OR，1.16；95%CI，0.85 - 1.58；P = 0.25）。尽管与对照者相比，侵袭性PC病例中A等位基因更常见，但高分级和低分级PC病例（Gleason分级分别<7和≥7）之间的等位基因频率相似。对于微卫星标记DG8S737，-8等位基因在家族性PC中显著更常见（OR，1.68；95%CI，1.09 - 2.60；P = 0.031），而-10等位基因在侵袭性PC中更常见（OR，2.85；95%CI，1.52 - 5.36；P = 0.0004）。单倍型分析显示，家族性PC（P = 0.006）和侵袭性PC（P = 0.005）病例与对照者之间的单倍型频率存在显著差异。-8/A单倍型与家族性PC的关联最强（P = 0.008），而-10/A单倍型与侵袭性PC的关联最强（P = 0.00005）。这些结果进一步证实了这两个多态性变异体（rs1447295和DG8S737）作为PC风险因素的重要性。然而，解释这种风险增加的机制尚未明确。
