***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Plasma levels of insulin-like growth factor-I ( IGF-I ) have been associated with the risk of prostate cancer . However , the association of IGF-I with specific tumor stage and grade at diagnosis , which correlate with risk of recurrence and mortality , has not been studied rigorously . To determine whether plasma levels of IGF-I and its main circulating binding protein , IGF binding protein-3 ( IGFBP-3 ) , predict more aggressive forms of prostate cancer , we investigated the association between plasma levels of each and specific stages and grade s of prostate cancer . METHODS We examined 530 case patients and 534 control subjects in a nested case-control study in the prospect i ve Physicians ' Health Study . Patients with prostate cancer diagnosed from 1982 through 1995 were matched to control subjects by age and smoking status  . IGF-I and IGFBP-3 were measured in prospect ively collected plasma sample s. Conditional logistic regression models were used to estimate the relative risks ( RRs ) for prostate cancer associated with IGF-I and IGFBP-3 , stratified on grade ( Gleason score > or = 7 versus < 7 ) and stage ( early = stage A or B prostate cancer versus advanced = stage C or D prostate cancer ) . All statistical tests were two-sided . RESULTS Plasma levels of IGF-I and IGFBP-3 were predictors of advanced-stage prostate cancer ( RR = 5.1 , 95 % confidence interval [ CI ] = 2.0 to 13.2 for highest versus lowest quartiles of IGF-I ; RR = 0.2 , 95 % CI = 0.1 to 0.6 for highest versus lowest quartiles of IGFBP-3 ) but not of early-stage prostate cancer . Neither was differentially associated with Gleason score . Men with high IGF-I levels and low IGFBP-3 levels had an RR for advanced-stage prostate cancer of 9.5 ( 95 % CI = 1.9 to 48.4 ) compared with men with low levels of both . Combining IGF-I and IGFPB-3 measurements with a st and ard prostate-specific antigen ( PSA ) measurement for prostate cancer screening increased the specificity ( from 91 % to 93 % ) but decreased sensitivity ( from 40 % to 36 % ) compared with measurement of PSA alone . CONCLUSIONS Circulating levels of IGF-I and IGFBP-3 may predict the risk of developing advanced-stage prostate cancer , but their utility for screening patients with incident prostate cancer may be limited 5 Background : It is largely unknown whether prostate-specific antigen at first date of testing predicts long-term risk of prostate cancer incidence and mortality in the general population . We tested the hypothesis that baseline prostate-specific antigen levels predict long-term risk of prostate cancer incidence and mortality . METHODS Using a prospect i ve study , we examined 4383 20 - 94 year old men from the Danish general population followed in the Copenhagen City Heart Study from 1981 through 2009 .  Prostate-specific antigen was measured in plasma sample s obtained in 1981 - 83 . RESULTS During 28 years of follow-up , 170 men developed prostate cancer and 94 died from prostate cancer . Median follow-up was 18 years ( range 0.5 - 28 years ) . For prostate cancer incidence , the subhazard ratio was 3.0 ( 95 % confidence interval ( CI ) 1.9 - 4.6 ) for a prostate-specific antigen level of 1.01 - 2.00 ng/ml , 6.8 ( 4.2 - 11 ) for 2.01 - 3.00 ng/ml , 6.6 ( 3.4 - 13 ) for 3.01 - 4.00 ng/ml , 16 ( 10.4 - 25 ) for 4.01 - 10.00 ng/ml , and 57 ( 32 - 104 ) for > 10.00 ng/ml versus 0.01 - 1.00 ng/ml .. For prostate cancer mortality , corresponding subhazard ratios were 2.2 ( 1.3 - 3.9 ) , 5.1 ( 2.8 - 9.0 ) , 4.2 ( 1.8 - 10 ) , 7.0 ( 3.8 - 14 ) , and 14 ( 6.0 - 32 ) . For men with prostate-specific antigen levels of 0.01 - 1.00 ng/ml , absolute 10-year risk of prostate cancer was 0.6 % for age < 45 years , 0.7 % for 45 - 49 years , 1.1 % for 50 - 54 years , 1.2 % for 55 - 59 years , 1.3 % for 60 - 64 years , 1.1 % for 65 - 69 years , 1.3 % for 70 - 74 years , and 1.5 % for age≥75 years ; corresponding values for prostate-specific antigen levels > 10.00 ng/ml were 35 % , 41 % , 63 % , 71 % , 77 % , 69 % , 75 % , and 88 % , respectively . CONCLUSIONS Stepwise increases in prostate-specific antigen at first date of testing predicted a 3 - 57 fold increased risk of prostate cancer , a 2 - 16 fold increased risk of prostate cancer mortality , and a 35 - 88 % absolute 10-year risk of prostate cancer in those with prostate-specific antigen levels > 10.00 ng/ml . Equally important , absolute 10-year risk of prostate cancer in those with levels 0.01 - 1.00 ng/ml was only 0.6 - 1.5 % BACKGROUND Risk-stratified screening for prostate cancer ( PCa ) with prostate-specific antigen ( PSA ) testing incorporating genetic variants has received some attention but has been scarcely investigated . We developed a model to stratify the Finnish population by different risk profiles related to genetic variants to optimize the screening policy . METHODS Data from the Finnish r and omized controlled trial on screening for PCa with PSA testing were used to estimate a six-state Markov model of disease progression . Blood sample s from Finnish men were used to assess the risk of PCa related to three genetic variants ( rs4242382 , rs138213197 , and rs200331695 ) . A risk score-based approach combined with a series of computer simulation models was applied to optimize individual screening policies . RESULTS The 10-year risk of having progressive prostate cancer detected ranged from 43 % in the top 5 % risk group to approximately 11 % in the bottom half of the population . Using the median group , with screening every four years beginning at 55 years-old , as the reference group , the recommended age beginning screening was approximately 47 years-old for the top 5 % risk group and 55 years-old for those in the lower 60 % risk group . The recommended interscreening interval has been shortened for individuals in the high risk group . The increased availability of genomic information allows the proposed multistate model to be more discriminating with respect to risk stratification and the suggested screening policy , particularly for the lowest risk groups- . -- CONCLUSIONS A multi-state genetic variant-based model was developed for further application to population risk stratification to optimize the interscreening interval and the age at which to begin screening for PSA . A small sub-group of the population is likely to benefit from more intensive screening with early start and short interval , while half of the population is unlikely to benefit from such protocol ( compared with four-year interval after age 55 years ) Summary In this paper , we develop a Markov chain model to estimate parameters pertaining to the natural history of nasopharyngeal carcinoma ( NPC ) . The model is of progression from no disease to Epstein – Barr virus ( EBV ) infection , pre clinical screen-detectable tumour and clinical tumour . We derive tentative estimates of the parameters of the model , based on limited published data , to assess the efficacy of serum screening in conjunction with clinical assessment ( indirect mirror examination for NPC ) , for example the average duration of the pre clinical screen-detectable phase is estimated as 3.1 years . We further apply these parameters to a hypothetical screening trial in the Hong Kong population to assess the efficacy of  serum screening  with clinical assessment by different combinations of screening regime . Results suggest : ( 1 ) there is no substantial difference between 3-yearly and 6-yearly serum screening ; and ( 2 ) within the same serum screening regime annual and 3-yearly clinical assessment can prevent 33 % and 28 % of deaths from NPC respectively . Prediction of deaths and surrogate end points can be used to estimate the required sample size and duration for design ing a r and omized trial of screening for NPC . Based on these findings and power projections , we suggest a design for a r and omized trial in a high incidence area such as Hong Kong BACKGROUND The aim of the present study was to evaluate the future cumulative risk of prostate cancer in relation to levels of prostate-specific antigen ( PSA ) in blood and to determine whether this information could be used to individualize the PSA testing interval . METHODS The study included 5855 of 9972 men ( aged 50 - 66 years ) who accepted an invitation to participate in a prospect i ve , r and omized study of early detection for prostate cancer . We used a protocol based on biennial PSA measurements starting from 1995 and 1996 . Men with serum PSA levels of 3.0 ng/mL or more were offered  prostate biopsies . RESULTS Among the 5855 men , 539 cases of prostate cancer ( 9.2 % ) were detected after a median follow-up of 7.6 years ( up to July 1 , 2003 ) . Cancer detection rates during the follow-up period in relation to PSA levels were as follows : 0 to 0.49 ng/mL , 0 % ( 0/958 ) ; 0.50 to 0.99 ng/mL , 0.9 % ( 17/1992 ) ; 1.00 to 1.49 ng/mL , 4.7 % ( 54/1138 ) ; 1.50 to 1.99 ng/mL , 12.3 % ( 70/571 ) ; 2.00 to 2.49 ng/mL , 21.4 % ( 67/313 ) ; 2.50 to 2.99 ng/mL , 25.2 % ( 56/222 ) ; 3.00 to 3.99 ng/mL , 33.3 % ( 89/267 ) ; 4.00 to 6.99 ng/mL , 38.9 % ( 103/265 ) ; 7.00 to 9.99 ng/mL , 50.0 % ( 30/60 ) ; and for men with an initial PSA of 10.00 ng/mL or higher , 76.8 % ( 53/69 ) . Not a single case of prostate cancer was detected within 3 years in 2950 men ( 50.4 % of the screened population ) with an initial PSA level less than 1 ng/mL. CONCLUSIONS Retesting intervals should be individualized on the basis of the PSA level , and the large group of men with PSA levels of less than 1 ng/mL can safely be scheduled for a 3-year testing interval We followed our initial genome-wide association study ( GWAS ) of 527,869 SNPs on 1,172 individuals with prostate cancer and 1,157 controls of European origin — nested in the Prostate , Lung , Colorectal , and Ovarian ( PLCO ) Cancer Screening Trial prospect i ve study —by testing 26,958 SNPs  in four independent studies ( total of 3,941 cases and 3,964 controls ) . In the combined joint analysis , we confirmed three previously reported loci ( two independent SNPs at 8q24 and one in HNF1B ( formerly known as TCF2 on 17q ) ; P < 10−10 ) . In addition , loci on chromosomes 7 , 10 ( two loci ) and 11 were highly significant ( between P < 7.31 × 10−13 and P < 2.14 × 10−6 ) . Loci on chromosome 10 include MSMB , which encodes β-microseminoprotein , a primary constituent of semen and a proposed prostate cancer biomarker , and CTBP2 , a gene with antiapoptotic activity ; the locus on chromosome 7 is at JAZF1 , a transcriptional repressor that is fused by chromosome translocation to SUZ12 in endometrial cancer . Of the nine loci that showed highly suggestive associations ( P < 2.5 × 10−5 ) , four best fit a recessive model and included c and i date susceptibility genes : CPNE3 , IL16 and CDH13 . Our findings point to multiple loci with moderate effects associated with susceptibility to prostate cancer that , taken together , in the future may predict high risk in select individuals As with wide-spread use of prostate cancer ( Pca ) screening with prostate-specific antigen testing , overdetection has increasingly gained attention . The authors aim ed to estimate absolute risk of overdetection ( RO ) in  Pca screening  with various interscreening intervals and ages at start of screening . We estimated age-specific pre clinical incidence rates ( per 100,00 
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4 ) Conclusions : Gene‒PSA-guided personalized screening for PrCa leads to fewer unnecessary PSA tests without compromising the benefits of mortality reduction ( as happens with the universal screening program )