Polygenic risk score improves prostate cancer risk prediction: results from the Stockholm-1 cohort study.
Polygenic risk score improves prostate cancer risk prediction: results from the Stockholm-1 cohort study.
复制标题
DOI：
10.1016/j.eururo.2011.01.017
复制
发表时间：
2011-07
期刊：
影响因子：
23.4
通讯作者：
Gronberg, Henrik
中科院分区：
文献类型：
--
作者：
Aly, Markus;Wiklund, Fredrik;Xu, Jianfeng;Isaacs, William B.;Eklund, Martin;D'Amato, Mauro;Adolfsson, Jan;Gronberg, Henrik
在美国，每年进行超过100万次前列腺活检。前列腺特异性抗原（PSA）的低特异性导致在没有前列腺癌（PCa）的男性中进行诊断性活检。其他信息，如遗传标记，可以用来避免不必要的活检。确定与PCa相关的单核苷酸多态性（SNP）是否可用于确定是否需要前列腺活检。斯德哥尔摩-1队列（n = 5241）包括2005年至2007年期间接受前列腺活检的男性。从数据库中检索PSA水平，并使用问卷调查获得家族史。对35个经过验证的SNP进行了分析，并将其转换为遗传风险评分，并在风险预测模型中实施。当比较非遗传模型（基于年龄，PSA，游离总PSA和家族史）与遗传模型并使用固定数量的检测到的PCa病例时，发现遗传模型需要的活检比非遗传模型少得多，避免了480次活检（22.7%），代价是在3%的患者中错过了PCa诊断，这些患者的特征是患有侵袭性疾病。然而，总体遗传模型并不区分攻击性病例和非攻击性病例。虽然遗传模型比非遗传模型减少了活检的数量，但这一发现的临床意义需要进一步评估。
More than 1 million prostate biopsies are conducted yearly in the United States. The low specificity of prostate-specific antigen (PSA) results in diagnostic biopsies in men without prostate cancer (PCa). Additional information, such as genetic markers, could be used to avoid unnecessary biopsies. To determine whether single nucleotide polymorphisms (SNPs) associated with PCa can be used to determine whether biopsy of the prostate is necessary. The Stockholm-1 cohort (n = 5241) consisted of men who underwent a prostate biopsy during 2005 to 2007. PSA levels were retrieved from databases and family histories were obtained using a questionnaire. Thirty-five validated SNPs were analysed and converted into a genetic risk score that was implemented in a risk-prediction model. When comparing the nongenetic model (based on age, PSA, free-to-total PSA, and family history) with the genetic model and using a fixed number of detected PCa cases, it was found that the genetic model required significantly fewer biopsies than the nongenetic model, with 480 biopsies (22.7%) avoided, at a cost of missing a PCa diagnosis in 3% of patients characterised as having an aggressive disease. However, the overall genetic model does not discriminate between aggressive and nonaggressive cases. Although the genetic model reduced the number of biopsies more than the nongenetic model, the clinical significance of this finding requires further evaluation.
登录
查看更多内容
影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
12.3
作者：
Wiklund F
通讯作者：
Wiklund F
影响因子：
30.8
作者：
Gudmundsson, Julius;Sulem, Patrick;Gudbjartsson, Daniel F.;Blondal, Thorarinn;Gylfason, Arnaldur;Agnarsson, Bjarni A.;Benediktsdottir, Kristrun R.;Magnusdottir, Droplaug N.;Orlygsdottir, Gudbjorg;Jakobsdottir, Margret;Stacey, Simon N.;Sigurdsson, Asgeir;Wahlfors, Tiina;Tammela, Teuvo;Breyer, Joan P.;McReynolds, Kate M.;Bradley, Kevin M.;Saez, Berta;Godino, Javier;Navarrete, Sebastian;Fuertes, Fernando;Murillo, Laura;Polo, Eduardo;Aben, Katja K.;van Oort, Inge M.;Suarez, Brian K.;Helfand, Brian T.;Kan, Donghui;Zanon, Carlo;Frigge, Michael L.;Kristjansson, Kristleifur;Gulcher, Jeffrey R.;Einarsson, Gudmundur V.;Jonsson, Eirikur;Catalona, William J.;Mayordomo, Jose I.;Kiemeney, Lambertus A.;Smith, Jeffrey R.;Schleutker, Johanna;Barkardottir, Rosa B.;Kong, Augustine;Thorsteinsdottir, Unnur;Rafnar, Thorunn;Stefansson, Kari
通讯作者：
Stefansson, Kari
影响因子：
30.8
作者：
Eeles, Rosalind A.;Kote-Jarai, Zsofia;Easton, Douglas F.
通讯作者：
Easton, Douglas F.
影响因子：
30.8
作者：
Al Olama, Ali Amin;Kote-Jarai, Zsofia;Easton, Douglas F.
通讯作者：
Easton, Douglas F.