Genetic polymorphisms at 19q13.33 are associated with [-2]proPSA (p2PSA) levels and provide additional predictive value to prostate health index for prostate cancer.
Genetic polymorphisms at 19q13.33 are associated with [-2]proPSA (p2PSA) levels and provide additional predictive value to prostate health index for prostate cancer.
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19q13.33的遗传多态性与[-2]proPSA（p2PSA）水平相关，并为前列腺癌的前列腺健康指数提供额外的预测价值。
DOI：
10.1002/pros.24192
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Na R
中科院分区：
文献类型：
--
作者：
Huang D;Ruan X;Wu Y;Lin X;Huang J;Ye D;Gao Y;Ding Q;Xu D;Na R
前列腺健康指数（phi）是[−2]proPSA（p2PSA）的衍生物，在前列腺癌（PCa）检测中显示出比前列腺特异性抗原（PSA）更好的准确性。本研究旨在探讨先前鉴定的PSA相关单核苷酸多态性（SNP）是否影响p2PSA或phi水平并导致潜在的临床应用。我们对2013年8月至2019年3月在三家三级医疗中心接受前列腺活检的2268例连续患者进行了一项观察性前瞻性研究。采用线性回归法对46个具有± 100 kb窗口的候选基因的基因分型数据与p2PSA和phi水平的相关性进行了检验。进行多变量logistic回归模型，并使用重复十倍交叉验证进行内部验证。我们进一步根据显着的基因型计算了个性化的phi截止值。使用决策曲线分析和净重新分类改进（NRI）指数评估判别性能。我们在19q13.33检测到11个显著变异，这些变异与p2PSA相关，与PCa无关。最显著的SNP，KLK 2中的rs198978（P组合= 5.73 × 10−9），也与phi值相关（P组合= 3.20 × 10−6）。与两个常用的phi临界值27.0和36.0相比，个性化phi临界值在携带变异型的男性中具有显著的PCa NRI，范围为5.23%至9.70%（均p <0.01）。Rs198978与p2PSA值独立相关，并可使用个性化临界值提高phi对PCa的诊断能力。
Prostate health index (phi), a derivative of [−2]proPSA (p2PSA), has shown better accuracy than prostate‐specific antigen (PSA) in prostate cancer (PCa) detection. The present study was to investigate whether previously identified PSA‐associated single nucleotide polymorphisms (SNPs) influence p2PSA or phi levels and lead to potential clinical utility. We conducted an observational prospective study with 2268 consecutive patients who underwent prostate biopsy in three tertiary medical centers from August 2013 to March 2019. Genotyping data of the 46 candidate genes with a ± 100 kb window were tested for association with p2PSA and phi levels using linear regression. Multivariable logistic regression models were performed and internally validated using repeated tenfold cross‐validation. We further calculated personalized phi cutoff values based on the significant genotypes. Discriminative performance was assessed using decision curve analysis and net reclassification improvement (NRI) index. We detected 11 significant variants at 19q13.33 which were p2PSA‐associated independent of PCa. The most significant SNP, rs198978 in KLK2 (P combined = 5.73 × 10−9), was also associated with phi values (P combined = 3.20 × 10−6). Compared to the two commonly used phi cutoffs of 27.0 and 36.0, the personalized phi cutoffs had a significant NRI for PCa ranged from 5.23% to 9.70% among men carrying variant types (all p < .01). Rs198978, is independently associated with p2PSA values, and can improve the diagnostic ability of phi for PCa using personalized cutoff values.
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影响因子：
5.3
作者：
Kote-Jarai Z;Amin Al Olama A;Leongamornlert D;Tymrakiewicz M;Saunders E;Guy M;Giles GG;Severi G;Southey M;Hopper JL;Sit KC;Harris JM;Batra J;Spurdle AB;Clements JA;Hamdy F;Neal D;Donovan J;Muir K;Pharoah PD;Chanock SJ;Brown N;Benlloch S;Castro E;Mahmud N;O'Brien L;Hall A;Sawyer E;Wilkinson R;Easton DF;Eeles RA
通讯作者：
Eeles RA
影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
影响因子：
23.4
作者：
Aly, Markus;Wiklund, Fredrik;Xu, Jianfeng;Isaacs, William B.;Eklund, Martin;D'Amato, Mauro;Adolfsson, Jan;Gronberg, Henrik
通讯作者：
Gronberg, Henrik
影响因子：
6.4
作者：
Johansson, Mattias;Holmstrom, Benny;Stattin, Par
通讯作者：
Stattin, Par
DOI：
10.1093/jnci/95.12.868
发表时间：
2003-06-18
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Draisma, G;Boer, R;de Koning, HJ
通讯作者：
de Koning, HJ