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Clinical validity and utility of genetic risk scores in prostate cancer

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Asian Journal of Andrology 2016年第4期18卷 509-514页

作者： br.an t.helfand James Kearns Carly Conran Jianfeng Xu Department of Surgery NorthShore University HealthSystem Program for Personalized Cancer Care Evanston IL 60201 USA.

Current issues related to prostate cancer （PCa） clinical care （e.g., over-screening, over-diagnosis, and over-treatment of nonaggressive PCa） call for risk assessment tools that can be combined with family history （FH） to stratify disease risk among men in the general population. Since 2007, genome-wide association studies （GWASs） have identified more than 100 SNPs associated with PCa susceptibility. In this review, we discuss （1） the validity of these PCa risk-associated SNPs, individually and collectively; （2） the various methods used for measuring the cumulative effect of multiple SNPs, including genetic risk score （GRS）; （3） the adequate number of SNPs needed for risk assessment; （4） reclassification of risk based on evolving numbers of SNPs used to calculate genetic risk, （5） risk assessment for men from various racial groups, and （6） the clinical utility of genetic risk assessment. In conclusion, data available to date support the clinical validity of PCa risk-associated SNPs and GRS in risk assessment among men with or without FH. PCa risk-associated SNPs are not intended for diagnostic use; rather, they should be used the same way as FH. Combining GRS and FH can significantly improve the performance of risk assessment. Improved risk assessment may have important clinical utility in targeted PCa testing. However, clinical trials are urgently needed to evaluate this clinical utility as well as the acceptance of GRS by patients and physicians.

关键词： genetic risk score prostate cancer pyramid model single nucleotide polymorphisms

Risk assessment of venous thromboembolism in inflammatory bowel disease by inherited risk in a population-based incident cohort

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World Journal of Gastroenterology 2023年第39期29卷 5494-5502页

作者： Andrew S Rifkin Zhuqing Shi Jun Wei Siqun Lilly Zheng br.an t.helfand Jonathan S Cordova Vincent F Biank Alfonso J tafur Omar Khan Jianfeng Xu Program for Personalized Cancer Care NorthShore University HealthSystemEvanstonIL 60201United States Department of Surgery NorthShore University HealthSystemEvanstonIL 60201United States Pritzker School of Medicine University of ChicagoChicagoIL 60637United States Department of Pediatrics NorthShore University HealthSystemEvanstonIL 60201United States Cardiovascular Institute NorthShore University HealthSystemEvanstonIL 60201United States Department of Medicine NorthShore University HealthSystemEvanstonIL 60201United States

Inflammatory bowel disease(IBD),including Crohn’s disease(CD)and ulcerative colitis(UC),is a chronic inflammatory disease of the digestive tract with increasing prevalence *** venous thromboembolism(VtE)is a major complication in IBD patients,it is often underappreciated with limited tools for risk *** to estimate the proportion of VtE among IBD patients and assess genetic risk factors(monogenic and polygenic)for *** Incident VtE was followed for 8465 IBD patients in the UK Biobank(UKB).the associations of VtE with F5 factor V leiden(FVL)mutation,F2 G20210A prothrombin gene mutation(PGM),and polygenic score(PGS003332)were tested using Cox hazards regression analysis,adjusting for age at IBD diagnosis,gender,and genetic background(top 10 principal components).the performance of genetic risk factors for discriminating VtE diagnosis was estimated using the area under the receiver operating characteristic curve(AUC).RESULtS the overall proportion of incident VtE was 4.70%in IBD patients and was similar for CD(4.46%),UC(4.49%),and unclassified(6.42%),and comparable to that of cancer patients(4.66%)who are well-known at increased risk for *** carriers of F5/F2 had a significantly increased risk for VtE compared to non-mutation carriers,hazard ratio(HR)was 1.94,95%confidence interval(CI):*** contrast,patients with the top PGS decile had a considerably higher risk for VtE compared to those with intermediate scores(middle 8 deciles),HR was 2.06(95%CI:1.57-2.71).the AUC for differentiating VtE diagnosis was 0.64(95%CI:0.61-0.67),0.68(95%CI:0.66-0.71),and 0.69(95%CI:0.66-0.71),respectively,for F5/F2 mutation carriers,PGS,and *** Similar to cancer patients,VtE complications are common in IBD *** provides more informative risk information than F5/F2 mutations(FVL and PGM)for personalized thromboprophylaxis.

关键词： Inflammatory bowel disease Venous thromboembolism Polygenic score Factor V leiden Prothrombin gene mutation

Prostate volume does not provide additional predictive value to prostate health index for prostate cancer or clinically significant prostate cancer:results from a multicenter study in China

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Asian Journal of Andrology 2020年第5期22卷 539-543页

作者： Da Huang Yi-Shuo Wu Ding-Wei Ye Jun Qi Fang Liu br.an t.helfand Siqun L Zheng Qiang Ding Dan-Feng Xu Rong Na Jian-Feng Xu Ying-Hao Sun Department of Urology Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Department of Urology Huashan HospitalFudan UniversityShanghai 200040China Fudan Institute of Urology Huashan HospitalFudan UniversityShanghai 200040China Department of Urology Shanghai Cancer CenterFudan UniversityShanghai 200032China Department of Urology Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China Division of Urology NorthShore University Health SystemEvanstonIL 60201USA Program for Personalized Cancer Care NorthShore University Health SystemEvanstonIL 60201US A Departm ent of Urology Shanghai Changhai HospitalThe Second Military Medical UniversityShanghai 2CXD433China.

to evaluate whether prostate volume(PV)would provide additional predictive utility to the prostate health index(phi)for predicting prostate cancer(PCa)or clinically significant prostate cancer,we designed a prospective,observational multicenter study in two prostate biopsy *** 1 included 595 patients from three medical centers from 2012 to 2013,and Cohort 2 included 1025 patients from four medical centers from 2013 to *** under the receiver operating characteristic curves(AUC)and logistic regression models were used to evaluate the predictive performance of PV-based derivatives and *** regression analysis showed that both total prostate-specific antigen(tPSA)and free PSA(fPSA)were significantly correlated with PV(all Ptly correlated with PV in Cohort 2(Pt not in Cohort 1(P=0.309),while no significant association was observed between phi and *** combining phi with PV,phi density(PHID)and another phi derivative(PHIV,calculated as phi/PV°5)did not outperform phi for predicting PCa or clinically significant PCa in either Cohort 1 or Cohort *** regression analysis also showed that phi and PV were independent predictors for both PCa and clinically significant PCa(all Pt provide additional predictive value to phi when combining these derivatives in a regression model(all models vs phi were not statistically significant,all P>0.05).In conclusion,PV-based derivatives(both PHIV and PHID)and models incorporating PV did not improve the predictive abilities of phi for either PCa or clinically significant PCa.

关键词： China prostate cancer prostate health index prostate volume

Race-specific genetic risk score is more accurate than nonrace-specific genetic risk score for predicting prostate cancer and high-grade diseases

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Asian Journal of Andrology 2016年第4期18卷 525-529页

作者： Rong Na Dingwei Ye Jun Qi Fang Liu Xiaoling Lin br.an t.helfand Charles B brendler Carly Conran Jian Gong Yishuo Wu Xu Gao Yaqing Chen S Lilly Zheng Zengnan Mo Qiang Ding Yinghao Sun Jianfeng Xu Department of Urology Huashan Hospital Fudan University Shanghai China Fudan Institute of Urology Huashan Hospital Fudan University Shanghai China Program for Personalized Cancer Care NorthShore University HealthSystem Evanston Illinois USA Health Communication Institute School of Public Health Fudan University Shanghai China Department of Urology Shanghai Cancer Center Fudan University Shanghai China Department of Urology Xinhua Hospital Shanghai Jiaotong University School of Medicine Shanghai China Division of Urology NorthShore University HealthSystem Evanston Illinois USA Department of Urology Shanghai Changhai Hospital The Second Military Medical University Shanghai China Department of Medical Ultrasonic Xinhua Hospital Shanghai Jiaotong University School of Medicine Shanghai China Center for Genomic and Personalized Medicine Guangxi Medical University Nanning China

Genetic risk score （GRS） based on disease risk-associated single nucleotide polymorphisms （SNPs） is an informative tool that can be used to provide inherited information for specific diseases in addition to family history, However, it is still unknown whether only SNPs that are implicated in a specific racial group should be used when calculating GRSs. the objective of this study is to compare the performance of race-specific GRS and nonrace-specitic GRS for predicting prostate cancer （PCa） among 1338 patients underwent prostate biopsy in Shanghai, China. A race-specific GRS was calculated with seven PCa risk-associated SNPs implicated in East Asians （GRS7）, and a nonrace-specific GRS was calculated based on 76 PCa risk-associated SNPs implicated in at least one racial group （GRS76）. the means of GRS7 and GRS76 were 1.19 and 1.85, respectively, in the study population. Higher GRS7 and GRS76 were independent predictors for PCa and high-grade PCa in univariate and multivariate analyses. GRS7 had a better area under the receiver-operating curve （AUC） than GRS76 for discriminating PCa （0.602 vs 0.573） and high-grade PCa （0.603 vs 0.575） but did not reach statistical significance. GRS7 had a better （up to 13% at different cutoffs） positive predictive value （PPV） than GRS76. In conclusion, a race-specific GRS is more robust and has a better performance when predicting PCa in East Asian men than a GRS calculated using SNPs that are not shown to be associated with East Asians.

关键词： Chinese genetic risk score genome-wide association study prostate cancer single nucleotide polymorphism