Plateau effect of prostate cancer risk‐associated SNPs in discriminating prostate biopsy outcomes

Ren, Shancheng; Xu, Jianfeng; Zhou, Tie; Jiang, Haowen; Chen, Haitao; Liu, Fang; Na, Rong; Zhang, Limin; Wu, Yishuo; Sun, Jielin; Yang, Bo; Gao, Xu; Zheng, S. Lilly; Xu, Chuanliang; Ding, Qiang; Sun, Yinghao

doi:10.1002/pros.22721

Cited by 29 publications

(43 citation statements)

References 53 publications

(86 reference statements)

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“…This may be attributed to the fact that certain risk variants were not strongly associated with PCa and others conferred a decreased effect to the risk of PCa in Chinese population compared with that in European whites. In a previous study, the plateau effect of PCa risk-associated SNPs was evaluated in predicting PCa in a Chinese population and it was identified that the predictive performance increased when the top 13 highest impact PCa risk-associated SNPs were included in the GRS (9). The results were similar in the present study; therefore, this may indicate that further SNPs weakly associated with PCa may not improve the predictive performance of GRS for PCa.…”

Section: Snpsupporting

confidence: 76%

“…Since these risk-associated single nucleotide polymorphisms (SNPs) exhibited a cumulative effect on PCa risk, the genetic risk scores (GRS) derived from PCa risk-associated SNPs were able to evaluate an individual's risk of PCa. The GRS based on the Chinese population is established and demonstrated to be a significant predictor of biopsy outcome in previous studies (5)(6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

“…With an increasing sample size used in GWAS through combined data, a meta-analysis of a multi-ethnic population, which included 87,040 individuals, identified 23 new susceptibility loci for PCa (including 15 9 and WEI MENG multiethnic and 1 in the early onset analysis) (10). These PCa risk-associated alleles exhibited decreased effects with odds ratios (ORs) ranging between 1.06 and 1.14 (10).…”

Section: Introductionmentioning

confidence: 99%

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Validation of the novel susceptibility loci for prostate cancer in a Chinese population

Chen

et al. 2017

Oncol Lett

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Abstract. The present study evaluated 23 newly identified susceptibility loci for prostate cancer (PCa) in a Chinese population and assessed whether any validated loci were associated with the genetic risk score (GRS) of PCa in a Chinese population. A total of 1,417 patients with PCa and 1,008 controls were recruited in the present study. The association of each single nucleotide polymorphism (SNP) with PCa risk and PCa aggressiveness was analyzed. The predictive ability of two GRSs based on 30 SNPs (GRS30) and the 9 most significant SNPs (GRS9) in the Chinese population were also compared. Among the 19 SNPs evaluated, 1 SNP (rs7153648 at 14q23) was associated with PCa risk [odds ratio (OR)=1.206, P<0.05)] and 1 SNP (rs636291 at 1p23) was associated with PCa aggressiveness (OR=1.123, P<0.05). GRS30 and GRS9 were significantly increased in patients with PCa compared with that among non-PCa controls. The areas under receiver operating characteristic curves of GRS9 and GRS 30 were similar (0.792 for GRS9 vs. 0.7994 for GRS30, P=0.138). To conclude, among the 19 SNPs evaluated, only 1 SNP was associated with PCa risk in the Chinese population. SNPs that were weakly associated with PCa were unlikely to improve the predictive ability of existing GRS in the Chinese population.

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Section: Snpsupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Validation of the novel susceptibility loci for prostate cancer in a Chinese population

Chen

et al. 2017

Oncol Lett

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“…However, only about 30–40% of men with abnormal PSA values or physical exam findings are routinely diagnosed with PC on transrectal ultrasound guided biopsy 53 . Recent studies have evaluated germline PC-risk SNPs to predict PC diagnosis on biopsy in men of European ancestry 54, 55 and different racial populations 56–58 . For example, Aly, et al evaluated a panel of 35 PC risk SNPs in over 5000 Swedish men who underwent a prostate biopsy.…”

Section: Germline Prostate Cancer Risk Variants and Biopsy Resultsmentioning

confidence: 99%

A genetic-based approach to personalized prostate cancer screening and treatment

Helfand

Catàlona²,

2015

Current Opinion in Urology

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Purpose Recent advances in sequencing technologies has allowed for the identification of genetic variants within germline DNA that can explain a significant portion of the genetic underpinnings of prostate cancer. Despite evidence suggesting that these genetic variants can be used for improved risk stratification, they have not yet been routinely incorporated into routine clinical practice. This review highlights their potential utility in prostate cancer screening. Recent Findings There are now almost 100 genetic variants, called single nucleotide polymorphisms (SNPs) that have been recently found to be associated with the risk of developing prostate cancer. In addition, some of these prostate cancer risk SNPs also have been found to influence PSA expression levels and potentially aggressive disease. Summary Incorporation of panels of prostate cancer risk SNPs into clinical practice offers potential to provide improvements in 1) patient selection for prostate cancer screening 2) PSA interpretation (e.g. by correcting for the presence of SNPs that influence PSA expression levels, 3) decision for biopsy (using PC-risk SNPs) and possibly the 4) decision for treatment. A proposed clinical algorithm incorporating these PC-risk SNPs is discussed.

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“…Higher GRS values have been consistently associated with an increased risk for many common diseases, including cancer and cardiovascular diseases. [4][5][6][7] In prostate cancer (PCa) for example, a significant dose-response effect between GRS percentiles (quartile, quintile, or deciles) and disease risk was consistently observed in many study populations, including large case-control studies, 4,8 retrospective analysis of prospective studies, 9,10 prostate biopsy cohorts, 11,12 and prospective studies. 13 These statistical associations provide an important basis for risk assessment, which we refer to as broad-sense validity.…”

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confidence: 99%

Concept and benchmarks for assessing narrow‐sense validity of genetic risk score values

Shi

et al. 2019

The Prostate

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Background While higher genetic risk score (GRS) has been statistically associated with increased disease risk (broad‐sense validity), the concept and tools for assessing the validity of reported GRS values from tests (narrow‐sense validity) are underdeveloped. Methods We propose two benchmarks for assessing the narrow‐sense validity of GRS. The baseline benchmark requires that the mean GRS value in a general population approximates 1.0. The calibration benchmark assesses the agreement between observed risks and estimated risks (GRS values). We assessed benchmark performance for three prostate cancer (PCa) GRS tests, derived from three SNP panels with increasing stringency of selection criteria, in a PCa chemoprevention trial where 714 of 3225 men were diagnosed with PCa during the 4‐year follow‐up. Results GRS from Panels 1, 2, and 3 were all statistically associated with PCa risk; P = 5.58 × 10−3, P = 1 × 10−3, and P = 1.5 × 10−13, respectively (broad‐sense validity). For narrow‐sense validity, the mean GRS value among men without PCa was 1.33, 1.09, and 0.98 for Panels 1, 2, and 3, respectively (baseline benchmark). For assessing the calibration benchmark, observed risks were calculated for seven groups of men with GRS values <0.3, 0.3–0.79, 0.8–1.19, 1.2‐1.49, 1.5‐1.99, 2‐2.99, and ≥3. The calibration slope (higher is better) was 0.15, 0.12, and 0.60, and the bias score (lower is better) between the observed risks and GRS values was 0.08, 0.08, and 0.02 for Panels 1, 2, and 3, respectively. Conclusion Performance differed considerably among GRS tests. We recommend that all GRS tests be evaluated using the two benchmarks before clinical implementation for individual risk assessment.

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Plateau effect of prostate cancer risk‐associated SNPs in discriminating prostate biopsy outcomes

Cited by 29 publications

References 53 publications

Validation of the novel susceptibility loci for prostate cancer in a Chinese population

Validation of the novel susceptibility loci for prostate cancer in a Chinese population

A genetic-based approach to personalized prostate cancer screening and treatment

Concept and benchmarks for assessing narrow‐sense validity of genetic risk score values

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