***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 
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    ***EXAMPLES*** 
    Input: Context Genetic and environmental risk assessment ( GERA ) , in which related genetic and environmental information identifies an individual 's risk for a disease , has been suggested as a means to motivate adherence to recommended cancer screening . Contribution This r and omized trial found that providing 1 specific GERA result to persons who were previously nonadherent to screening recommendations for colorectal cancer did not alter the subsequent rate of screening . Caution The study could assess only 1 set of GERA results and 1 method of communicating these results to patients . Implication Results of GERA can not be assumed to encourage adherence to recommended screening . The Editors Genetic testing for cancer susceptibility is offered most frequently for single-gene disorders . A mutation in the adenomatous polyposis coli gene ( APC ) confers a risk for colorectal cancer ( CRC ) of approximately 90 % ( 1 ) . Identification of this mutation substantially affects clinical practice . However , cancer usually does not arise from single mutations . Instead , susceptibility results from the modest contributions of many genes , usually with environmental interaction . Identification of these genes and their modifiers is an active area of research ( 2 ) . Genetic and environmental risk assessment ( GERA ) for common diseases is anticipated to become a widespread component of health care ( 3 , 4 ) . We assessed polymorphic variants of methylenetetrahydrofolate reductase (MTHFR),an important regulator of cellular folate metabolism . Specific MTHFR polymorphisms are associated with variable susceptibility to CRC ( 58 ) . Epidemiologic data also support a link between serum folate levels and CRC risk ( 9 ) . Assessment of the genetic ( MTHFR ) and environmental ( serum folate levels ) interaction is attractive because data that allow for CRC risk stratification among average-risk persons already exist . Specific polymorphisms in combination with low serum folate levels increase risk for CRC by approximately 1.5 to 2.0 times the baseline risk in white and African American persons in the United States ( 8) . Unlike with genetic testing for high-risk persons , such as those with familial adenomatous polyposis , little is known about the impact on health behaviors or the psychological effects of providing average-risk persons with moderately predictive genetic information ( 4 , 1013 ) . Underst and ing the benefits and harms of such testing in average-risk persons is important because similar testing is marketed directly to the public in an unsupervised manner ( 14 ) . We did a prospect i ve , r and omized , controlled trial to assess the effect of GERA feedback on CRC screening among average-risk persons who did not adhere to screening recommendations at study entry . Prevention of CRC is an optimal area to study the emerging role of moderately predictive genetic testing . Colorectal cancer is the second leading cause of cancer death in the United States ( 15 ) . Screening can reduce disease incidence and mortality ( 16 ) . Our primary hypothesis was that providing personalized GERA information would increase CRC screening uptake compared with usual care . Further , we anticipated that participants characterized as having elevated risk by GERA would undergo screening more than those at average risk . Although MTHFR and serum folate level testing provided personalized risk information , our study did not intend to evaluate the specific predictive value of this combination for colorectal neoplasia . Methods Design Overview We did a r and omized , controlled trial to compare CRC screening utilization in the  GERA group  versus the  usual care ( control ) group and to detect differences in screening proportion between the average- and elevated-risk GERA groups ( 12 ) . To increase the statistical power for comparisons within the GERA group , participants were r and omly assigned in a 2:1 ratio to GERA or usual care , respectively . Participants provided survey data at baseline , 3 weeks , and 6 months and agreed to medical record review to ascertain CRC screening status . Those in the GERA group also participated in GERA counseling and disclosure sessions and had blood drawn for genotyping and measurement of serum folate levels . Setting and Participants Participants in this institutional review boardapproved trial were recruited from 4 internal and family medicine practice s affiliated with Thomas Jefferson University , Philadelphia , Pennsylvania . We search ed scheduling , billing , and medical records data bases and applied filters matching eligibility requirements , including 1 ) age between 50 and 79 years ; 2 ) average-risk status for CRC , defined as being asymptomatic and having no history of colorectal adenomas , cancer , or inflammatory bowel disease or no family history of familial adenomatous polyposis , hereditary nonpolyposis CRC , or CRC in a first-degree relative ; 3 ) nonadherence to CRC screening guidelines at study initiation , defined as not having had home fecal occult blood testing in the past 12 months , barium enema or flexible sigmoidoscopy in the past 5 years , or colonoscopy in the past 10 years ; 4 ) not receiving antibiotics or antifolate medications ( for example , sulfasalazine or methotrexate ) within the past 6 weeks ; and 5 ) the ability to speak English . Potential participants were mailed a letter outlining the study ( Supplement 1 ) , a pamphlet review ing st and ard CRC screening options , a consent form , and information on how to opt out of the study . We telephoned participants who had not opted out , confirmed eligibility , obtained verbal consent , and administered a baseline survey about demographic characteristics and history of medical illnesses and multivitamin use . Participants also responded to previously described question naires about knowledge of CRC screening and the possible role of genes and diet in cancer development ( 17 ) . Finally , they completed the Impact of Event Scale ( IES ) question naire , a well-vali date d assessment tool for psychological distress ( 18 ) . Supplement 1 . Colon Cancer and Genetic and Environmental Risk Assessment R and omization and Intervention Study group allocation was implemented by a secure , Web-based application using r and omization tables generated before the study started . GERA Intervention Group Participants r and omly assigned to GERA  met with specially trained study nurses rather than genetic counselors . This research design reflected an effort to study feasible approaches to disclosure of genetic test results that could be incorporated into primary care setting s , because the number of genetic counselors seems inadequate to meet health service needs even in high-risk setting s ( 19 ) . Study nurses were trained by genetic counselors before study initiation and regularly monitored disclosure sessions to ensure process uniformity . Using a st and ardized study pamphlet describing GERA , the nurse and intervention participants together review ed the purpose of GERA , the potential results from genotyping and serum folate level measurement , and how results would be disclosed . A basic description of genes and their importance in cancer was provided . An average lifetime risk for CRC of 1 in 20 was described . Participants were told that their GERA results would be classified as elevated or average . The study nurse explained that an elevated result did not guarantee disease but was only one potential risk factor for CRC , suggesting modestly increased risk compared with that of a similarly aged person . Conversely , the nurse stated that an average result did not ensure protection against CRC now or in the future but simply indicated the absence of this risk factor . The study nurse emphasized that GERA was a method to stratify CRC risk but was not intended to be a substitute for screening . Venipuncture was done to assess serum folate levels and MTHFR polymorphisms for participants r and omly assigned to GERA .  Serum folate levels were analyzed in a single commercial laboratory using a st and ard 125I RIA kit with controls . All genotyping was done at the Fox Chase Cancer Center Cancer Genomics Facility , Philadelphia , Pennsylvania . After DNA was extracted , separate polymerase chain reaction amplifications of exons 4 and 7 of the MTHFR gene were completed , followed by pyrosequencing specific for codons 677 and 1298 . The GERA-associated CRC risk was characterized by particular combinations of age-specific serum folate levels and MTHFR polymorphisms ( Appendix Table 1 ) ; MTHFR is an important regulator of cellular folate metabolism . Separately , MTHFR polymorphic variant or serum folate level is associated with variable susceptibility to CRC ( 5 , 6 , 9 , 20 , 21 ) . Most persons with compound genotype combinations have a modestly elevated CRC risk in the setting of low serum folate levels compared with carriers of these same genotypes with normal serum folate levels or persons with less common combinations ( TT/AA and CC/CC ) , regardless of serum folate levels ( 8 , 22 , 23 ) . Low serum folate level status was conventionally assigned to any person in the 25th percentile or below for age-based population normal values , according to data from NHANES ( National Health and Nutrition Examination Survey ) at study commencement ( 24 ) . Appendix Table 1 . Compound Genotype Frequencies Within 2 weeks of blood collection , GERA results were disclosed and explained to every participant , first by telephone and then by mail ( Supplement 2 ) . In the disclosure session , the same points about multiple potential risk factors ( GERA being only one ) were emphasized , as was the importance of screening regardless of GERA result . Supplement 2 . Results Mailing Usual Care ( Control ) Group Usual care recipients completed the same baseline question naire as GERA recipients ; however , they did not meet with a study nurse , discuss GERA , participate in decision counseling , or provide a blood sample . Regardless of study group or risk , all participants were encouraged to have screening . Outcomes and Follow-up Control and intervention recipients subsequently received a BACKGROUND The effectiveness of surgery versus observation for men with localized prostate cancer detected by means of prostate-specific antigen ( PSA ) testing is not known . METHODS From November 1994 through January 2002 , we r and omly assigned 731 men with localized prostate cancer ( mean age , 67 years ; median PSA value , 7.8 ng per milliliter ) to radical prostatectomy or observation  and followed them through January 2010 . The primary outcome was all-cause mortality ; the secondary outcome was prostate-cancer mortality . RESULTS During the median follow-up of 10.0 years , 171 of 364 men ( 47.0 % ) assigned to radical prostatectomy  died , as compared with 183 of 367 ( 49.9 % ) assigned to observation ( hazard ratio , 0.88 ; 95 % confidence interval [ CI ] , 0.71 to 1.08 ; P=0.22 ; absolute risk reduction , 2.9 percentage points ) . Among men assigned to radical prostatectomy , 21 ( 5.8 % ) died from prostate cancer or treatment , as compared with 31 men ( 8.4 % ) assigned to observation ( hazard ratio , 0.63 ; 95 % CI , 0.36 to 1.09 ; P=0.09 ; absolute risk reduction , 2.6 percentage points ) . The effect of treatment on all-cause and prostate-cancer mortality did not differ according to age , race , coexisting conditions , self-reported performance status , or histologic features of the tumor . Radical prostatectomy was associated with reduced all-cause mortality among men with a PSA value greater than 10 ng per milliliter ( P=0.04 for interaction ) and possibly among those with intermediate-risk or high-risk tumors ( P=0.07 for interaction ) . Adverse events within 30 days after surgery occurred in 21.4 % of men , including one death . CONCLUSIONS Among men with localized prostate cancer detected during the early era of PSA testing  , radical prostatectomy did not significantly reduce all-cause or prostate-cancer mortality , as compared with observation , through at least 12 years of follow-up . Absolute differences were less than 3 percentage points . ( Funded by the Department of Veterans Affairs Cooperative Studies Program and others ; PIVOT Clinical Trials.gov number , NCT00007644 . ) Purpose : Although prostate-specific antigen ( PSA ) is the best biomarker for predicting prostate cancer , its predictive performance needs to be improved . Results from the Prostate Cancer Prevention Trial revealed the overall performance measured by the areas under curve of the receiver operating characteristic at 0.68 . The goal of the present study is to assess the ability of genetic variants as a PSA-independent method to predict prostate cancer risk . Experimental Design : We systematic ally evaluated all prostate cancer risk variants that were identified from genome-wide association studies  during the past year in a large population -based prostate cancer case-control study population in Sweden , including 2,893 prostate cancer patients and 1,781 men without prostate cancer . Results : Twelve single nucleotide polymorphisms were independently associated with prostate cancer risk in this Swedish study population . Using a cutoff of any 11 risk alleles or family history , the sensitivity and specificity for predicting prostate cancer were 0.25 and 0.86 , respectively . The overall predictive performance of prostate cancer using genetic variants , family history , and age , measured by areas under curve was 0.65 ( 95 % confidence interval , 0.63 - 0.66 ) , significantly improved over that of family history and age ( 0.61 % ; 95 % confidence interval , 0.59 - 0.62 ; P = 2.3 × 10−10 ) . Conclusion : The predictive performance for prostate cancer using genetic variants and family history is similar to that of PSA . The utility of genetic testing , alone and in combination with PSA levels , should be evaluated in large studies such as the European R and omized Study for Prostate Cancer trial and Prostate Cancer Prevention Trial BACKGROUND In 2008 , we reported that radical prostatectomy , as compared with watchful waiting , reduces the rate of death from pro 
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Conclusion : The evidence on currently available SNP panels is insufficient to assess analytic validity , and at best the panels assessed would add a small and clinical ly unimportant improvement to factors such as age and family history in risk stratification ( clinical validity ) .