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Genetic polymorphisms at 19q13.33 are associated with [−2]proPSA (p2PSA) levels and provide additional predictive value to prostate health index for prostate cancer
Author(s) -
Huang Da,
Ruan Xiaohao,
Wu Yishuo,
Lin Xiaoling,
Huang Jingyi,
Ye Dingwei,
Gao Yi,
Ding Qiang,
Xu Danfeng,
Na Rong
Publication year - 2021
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.24192
Subject(s) - prostate cancer , medicine , single nucleotide polymorphism , logistic regression , prostate , cutoff , snp , prostate biopsy , oncology , genotype , prostate specific antigen , cancer , biology , genetics , gene , physics , quantum mechanics
Abstract Background 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. Methods 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. Results 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). Conclusion Rs198978, is independently associated with p2PSA values, and can improve the diagnostic ability of phi for PCa using personalized cutoff values.