Prostate cancer susceptibility variants confer increased risk of disease progression.
Prostate cancer susceptibility variants confer increased risk of disease progression.
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DOI：
10.1158/1055-9965.epi-10-0268
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发表时间：
2010-09
期刊：
影响因子：
--
通讯作者：
Witte JS
中科院分区：
文献类型：
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作者：
Cheng I;Plummer SJ;Neslund-Dudas C;Klein EA;Casey G;Rybicki BA;Witte JS
全基因组关联研究已经确定了许多与前列腺癌风险相关的单核苷酸多态性（SNP）。我们的目标是确定这些SNP是否影响前列腺癌的进展。我们对788例接受根治性前列腺切除术（RP）或放射治疗（RT）的侵袭性前列腺癌患者进行了26个与前列腺癌风险相关的SNP基因分型。前列腺癌进展定义为基于RP患者治疗后前列腺特异性抗原水平>0.3 ng/ml或RT患者高于最低值2 ng/ml、开始激素治疗或转移的生化复发。我们通过考克斯比例风险回归评估了独立和联合SNP与疾病进展之间的关联。基于逐步回归分析，5个SNP（rs 12621278、rs629242、rs 9364554、rs 4430796、rs 5945572）与前列腺癌进展独立相关。最强的SNP是ITGA 6基因座中的rs 12621278，其与进展风险增加2.4倍相关（P = 0.0003）。当考虑这5个SNP的风险等位基因总和时，每个额外的等位基因与进展风险增加29%相关（95% CI = 1.12-1-47）。我们发现，最近突出的前列腺癌易感基因座的五个也影响前列腺癌的进展超出了已知的临床病理学预测。如果得到证实，这些遗传变异可能有助于澄清哪些肿瘤可能进展，并需要更积极的治疗，而不是那些可能对发病率或死亡率没有实质性影响的肿瘤。前列腺癌发展的遗传易感性变体也可能告知疾病进展。
Genome-wide association studies have identified numerous single nucleotide polymorphisms (SNPs) associated with the risk of prostate cancer. Our objective was to determine whether these SNPs impact 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 (RP) or radiation therapy (RT). Prostate cancer progression was defined as biochemical recurrence based on post-treatment prostate specific antigen levels >0.3 ng/ml for RP patients or 2 ng/ml increase above the nadir for RT patients, initiation of hormone treatment, or metastases. We assessed the association between independent and combined SNPs and disease progression by Cox proportional hazard regression. Five SNPs demonstrated independent associations with prostate cancer progression (rs12621278, rs629242, rs9364554, rs4430796, 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 a 29% increase in risk of progression (95% CI = 1.12-1-47). We found that five of the recently highlighted prostate cancer susceptibility loci also influence prostate cancer progression beyond known clinicopathological predictors. If confirmed, these genetic variants may help clarify which tumors are likely to progress and require more aggressive treatment in contrast to those that may not have substantial impact on morbidity or mortality. Genetic susceptibility variants for prostate cancer development may also inform disease progression.