Single-nucleotide polymorphisms based genetic risk score in the prediction of pancreatic cancer risk

BACKGROUND Disease-related single nucleotide polymorphisms(SNPs)based genetic risk score(GRS)has been proven to provide independent inherited risk other than family history in multiple cancer types.AIM To evaluate the potential of GRS in the prediction of pancreatic cancer risk.METHODS In this case-control study(254 cases and 1200 controls),we aimed to evaluate the association between GRS and pancreatic ductal adenocarcinoma(PDAC)risk in the Chinese population.The GRS was calculated based on the genotype information of 18 PDAC-related SNPs for each study subject(personal genotyping information of the SNPs)and was weighted by external odd ratios(ORs).RESULTS GRS was significantly different in cases and controls(1.96±3.84 in PDACs vs 1.09±0.94 in controls,P<0.0001).Logistic regression revealed GRS to be associated with PDAC risk[OR=1.23,95%confidence interval(CI):1.13-1.34,P<0.0001].GRS remained significantly associated with PDAC(OR=1.36,95%CI:1.06-1.74,P=0.015)after adjusting for age and sex.Further analysis revealed an association of increased risk for PDAC with higher GRS.Compared with low GRS(<1.0),subjects with high GRS(2.0)were 99%more likely to have PDAC(OR:1.99,95%CI:1.30-3.04,P=0.002).Participants with intermediate GRS(1.0-1.9)were 39%more likely to have PDAC(OR:1.39,95%CI:1.03-1.84,P=0.031).A positive trend was observed(P trend=0.0006).CONCLUSION GRS based on PDAC-associated SNPs could provide independent information on PDAC risk and may be used to predict a high risk PDAC population.

CD55 Variant Associated with Pegylated-interferonαTherapy Response in HBeAg-positive Chronic Hepatitis B Patients

Background and Aims:Only a small percentage of chronic hepatitis B(CHB)patients effectively respond to treatment with pegylated-interferon alpha(PegIFNα)or nucleos(t)ide analogues(NUCs).We aimed to detect the correlations of complement regulators-associated single-nucleotide polymorphisms(SNPs)with treatment response of hepatitis B e antigen(HBeAg)-positive CHB patients.Methods:A total of 1,763 HBeAg-positive CHB patients were enrolled,894 received PegIFNαfor at least 48 weeks and were followed up for 24 weeks,and 869 received NUCs for 104 weeks.For each patient,nine SNPs in genes encoding for complement regulators were determined and genotyped.To assess the cumulative effect of numerous SNPs,a polygenic score(PGS)was utilized.The correlations of SNPs and PGS with the levels of combined response(CR)and hepatitis B s antigen(HBsAg)loss were also investigated.Results:In PegIFNα-treated patients,an intronic SNP of CD55,rs28371597,was strongly related to CR,and the CR rate in rs28371597_GG genotype carriers was only approximately half that of rs28371597_GT/TT genotype carriers(20.29%vs.37.10%,p=2.00×10^(−3)).A PGS incorporating CD55_rs28371597 and two additional SNPs,CFB_rs12614 and STAT4_rs7574865,which had been considered as predictors for PegIFNαtreatment response before,was strongly correlated with the levels of CR(ptrend=7.94×10^(−6))and HBsAg loss(p-trend=9.40×10^(−3))in PegIFNα-treated patients.In NUCs-treated individuals,however,none of the nine SNPs were shown to be significantly linked to CHB treatment response.Conclusions:CD55_rs28371597 is a promising biomarker for predicting CHB patients’responsiveness to PegIFNαtherapy.The updated PGS may be used for optimizing CHB treatment.

Performance of the Prostate Health Index in predicting prostate biopsy outcomes among men with a negative digital rectal examination and transrectal ultrasonography

The [-2]proPSA （p2PSA） and its derivatives, the p2PSA-to-free PSA ratio （%p2PSA）, and the Prostate Health Index （PHI） have greatly improved discrimination between men with and without prostate cancer （PCa） in prostate biopsies. However, little is known about their performance in cases where a digital rectal examination （DRE） and transrectal ultrasonography （TRUS） are negative. A prospective cohort of 261 consecutive patients in China with negative DRE and TRUS were recruited and underwent prostate biopsies. A serum sample had collected before the biopsy was used to measure various PSA derivatives, including total prostate-specific antigen （tPSA）, free PSA, and p2PSA. For each patient, the free-to-total PSA ratio （%fPSA）, PSA density （PSAD）, p2PSA-to-free PSA ratio （%p2PSA）, and PHI were calculated. Discriminative performance was assessed using the area under the receiver operating characteristic curve （AUC） and the biopsy rate at 91% sensitivity. The AUC scores within the entire cohort with respect to age, tPSA, %fPSA, PSAD, p2PSA, %p2PSA, and PHI were 0.598, 0.751, 0.646, 0.789, 0.814, 0.808, and 0.853, respectively. PHI was the best predictor of prostate biopsy results, especially in patients with a tPSA of 10.1-20 ng ml-1. Compared with other markers, at a sensitivity of 91%, PHI was the most useful for determining which men did not need to undergo biopsy, thereby avoiding unnecessary procedures. The use of PHI could improve the accuracy of PCa detection by predicting prostate biopsy outcomes among men with a negative DRE and TRUS in China.

Prostate cancer antigen 3 and genetic risk score as markers for the detection of prostate cancer in the Chinese population

Dear Editor We report here the performance of prostate cancer antigen 3 （PCA3） and genetic risk score （GRS） in predicting prostate cancer （PCa） from the prostate biopsy. To the best of our knowledge, this is the first report of simultaneously evaluating these two biomarkers in the same study.