Melanoma Genetic Testing, Counseling, and Adherence to Skin Cancer Prevention and Detection Behaviors Effect of communicating genetic and phenotypic risk for type 2 diabetes in combination with lifestyle advice on objectively measured physical activity: protocol of a randomised controlled trial Trial Protocol: Communicating DNA-based risk assessments for Crohn's disease: a randomised controlled trial assessing impact upon stopping smoking Evaluation of a Brief Web-Based Genetic Feedback Intervention for Reducing Alcohol-Related Health Risks Associated with ALDH2 Outcome criteria in smoking cessation trials: proposal for a common standard. Genetic test feedback with weight control advice: study protocol for a randomized controlled trial Genetic and Environmental Risk Assessment and Colorectal Cancer Screening in an Average-Risk Population Personalized Genetic Risk Counseling to Motivate Diabetes Prevention Incorporating genetic susceptibility feedback into a smoking cessation program for African-American smokers with low income. Disclosure of Genetic Information and Change in Dietary Intake: A Randomized Controlled Trial Genetic Susceptibility Testing and Readiness to Control Weight: Results from a Randomized Controlled Trial Examining the impact of genetic testing for type 2 diabetes on health behaviors: study protocol for a randomized controlled trial A randomized trial of genetic and environmental risk assessment (GERA) for colorectal cancer risk in primary care: trial design and baseline findings. Explaining behavior change after genetic testing: the problem of collinearity between test results and risk estimates. Psychological impact of genetic testing for familial hypercholesterolemia within a previously aware population: A randomized controlled trial Impact of genetic testing on causal models of heart disease and arthritis: An analogue study Does Type 2 Diabetes Genetic Testing and Counseling Reduce Modifiable Risk Factors? A Randomized Controlled Trial of Veterans Efficacy of genotype notification to Japanese smokers on smoking cessation--an intervention study at workplace. GRADE guidelines: 3. Rating the quality of evidence. Health Behavior Changes After Genetic Risk Assessment for Alzheimer Disease: The REVEAL Study An intervention study of smoking cessation with feedback on genetic cancer susceptibility in Japan. Effect of communicating DNA based risk assessments for Crohn’s disease on smoking cessation: randomised controlled trial Psychological and Behavioural Impact of Genetic Testing Smokers for Lung Cancer Risk Application of aldehyde dehydrogenase 2 (ALDH2) genetic diagnosis in support of decreasing alcohol intake. Genetic susceptibility testing in smoking-cessation treatment: one-year outcomes of a randomized trial.
Background : Little is known about the impact of knowledge of CDKN2A and MC1R genotype on melanoma prevention behaviors like sun avoidance and skin examination in the context of familial melanoma . Methods : Seventy-three adults with a family history of melanoma were r and omly assigned to be offered individualized CDKN2A and MC1R genotyping results in the context of a genetic counseling session , or the st and ard practice of not being offered counseling or disclosure of genotyping results . Mixed effects or longitudinal logistic models were used to determine whether the intervention affected change in sun protection habits , skin examinations , and perception and beliefs related to melanoma risk , prevention , and genetic counseling . Results : All participants in the intervention group who attended genetic counseling sessions chose to receive their test results . From baseline to follow-up , participants in the intervention group reported an increase in the frequency of skin self-examinations compared with a slight decrease in the control group ( P = 0.002 ) . Participants in the intervention group reported a smaller decrease in frequency of wearing a shirt with long sleeves than did participants in the control group ( P = 0.047 ) . No effect of the intervention was noted for other outcomes . Conclusions : Feedback of CDKN2A and MC1R genotype among families without known pathogenic CDKN2A mutations does not seem to decrease sun protection behaviors . Impact : While disclosure of CDKN2A and MC1R genotype did not have negative effects on prevention , the benefits of communicating this information remain unclear . The small number of families who tested positive for CDKN2A mutations in this study is a limitation . Cancer Epidemiol Biomarkers Prev ; 22(4 ) ; 607–14 . © 2013 AACR Type 2 diabetes ( T2D ) is associated with increased risk of morbidity and premature mortality . Among those at high risk , incidence can be halved through healthy changes in behaviour . Information about genetic and phenotypic risk of T2D is now widely available . Whether such information motivates behaviour change is unknown . We aim to assess the effects of communicating genetic and phenotypic risk of T2D on risk-reducing health behaviours , anxiety , and other cognitive and emotional theory-based antecedents of behaviour change . In a parallel group , open r and omised controlled trial , approximately 580 adults born between 1950 and 1975 will be recruited from the on-going population -based , observational Fenl and Study ( Cambridgeshire , UK ) . Eligible participants will have undergone clinical , anthropometric , and psychosocial measurements , been genotyped for 23 single-nucleotide polymorphisms associated with T2D , and worn a combined heart rate monitor and accelerometer ( Actiheart ® ) continuously for six days and nights to assess physical activity .  Participants are r and omised to receive either st and ard lifestyle advice alone ( control group ) , or in combination with a genetic or a phenotypic risk estimate for T2D ( intervention groups ) . The primary outcome is objective ly measured physical activity . Secondary outcomes include self-reported diet , self-reported weight , intention to be physically active and to engage in a healthy diet , anxiety , diabetes-related worry , self-rated health , and other cognitive and emotional outcomes . Follow-up occurs eight weeks post-intervention . Values at follow-up , adjusted for baseline , will be compared between r and omised groups . This study will provide much needed evidence on the effects of providing information about the genetic and phenotypic risk of T2D . Importantly , it will be among the first to examine the impact of genetic risk information using a r and omised controlled trial design , a population -based sample , and an objective ly measured behavioural outcome . Results of this trial , along with recent evidence syntheses of similar studies , should inform policy concerning the availability and use of genetic risk information . Current Controlled Trials IS RCT Background Estimates of the risk of developing Crohn 's disease ( CD ) can be made using DNA testing for mutations in the NOD2 ( CARD15 ) gene , family history , and smoking status . Smoking doubles the risk of CD , a risk that is reduced by stopping . CD therefore serves as a timely and novel paradigm within which to assess the utility of predictive genetic testing to motivate behaviour change to reduce the risk of disease . The aim of the study is to describe the impact upon stopping smoking of communicating a risk of developing CD that incorporates DNA analysis . We will test the following main hypothesis : Smokers who are first degree relatives ( FDRs ) of CD prob and s are more likely to make smoking cessation attempts following communication of risk estimates of developing CD that incorporate DNA analysis , compared with an equivalent communication that does not incorporate DNA analysis . Methods / design A parallel groups r and omised controlled trial in which smokers who are FDRs of prob and s with CD are r and omly allocated in families to undergo one of two types of assessment of risk for developing CD based on either : i . DNA analysis , family history of CD and smoking status , orii . Family history of CD and smoking statusThe primary outcome is stopping smoking for 24 hours or longer in the six months following provision of risk information . The secondary outcomes are seven-day smoking abstinence at one week and six month follow-ups . R and omisation of 470 smoking FDRs of CD prob and s , with 400 followed up ( 85 % ) , provides 80 % power to detect a difference in the primary outcome of 14 % between r and omised arms , at the 5 % significance level . Discussion This trial provides one of the strongest tests to date of the impact of communicating DNA-based risk assessment on risk-reducing behaviour change . Specific issues regarding the choice of trial design are discussed . Trial Registration IS RCT N : IS RCT There is increasing interest in health interventions that incorporate genetic risk information . Although genetic feedback has been evaluated as an adjunct to smoking cessation interventions , its efficacy for reducing alcohol-related risks is unknown . The purpose of this study was to evaluate the feasibility , acceptability , and efficacy of a web-based alcohol intervention incorporating genetic feedback and risk information specific to ALDH2 genotype . The ALDH2 * 2 variant is associated with partial protection against alcohol dependence but confers significantly increased risk for alcohol-related cancers as a function of alcohol exposure . Two hundred Asian-American young adults were r and omly assigned to receive web-based personalized genetic feedback or attention-control feedback . Genetic feedback included health risk information specific to alcohol-related cancer or alcohol dependence , depending on genotype . Outcomes included postintervention drinking behavior and theoretical correlates of behavior change . Genetic feedback and risk information result ed in significant reductions in 30-day drinking frequency and quantity among participants with the ALDH2 * 1/*2 genotype . Genetic feedback was rated highly by participants and also showed some effects on theoretical correlates of behavior change . Results provide initial evidence of the feasibility , acceptability , and brief efficacy of web-based genetic feedback for reducing alcohol-related health risks associated with ALDH2 genotype Smoking  cessation treatment is now integrated into many health-care systems and a major research effort is under way to improve current success rates . Until now results from r and omized clinical trials have been reported in many different ways , leading to problems of interpretation . We propose six st and ard criteria comprising the ' Russell St and ard ' ( RS ) . These criteria are applicable to trials of cessation aids where participants have a defined target quit date and there is face-to-face contact with research ers or clinic staff , as follows . ( 1 ) Follow-up for 6 months ( RS6 ) or 12 months ( RS12 ) from the target quit date or the end of a predefined ' grace period ' ; ( 2 ) self-report of smoking abstinence over the whole follow-up period allowing up to five cigarettes in total ; ( 3 ) biochemical verification of abstinence at least at the 6-month or 12-month follow-up point ; ( 4 ) use of an ' intention-to-treat ' approach in which data from all r and omized smokers are included in the analysis unless they have died or moved to an untraceable address ( participants who are included in the analysis are counted as smokers if their smoking status at the final follow-up can not be determined ) ; ( 5 ) following-up ' protocol violators ' and using their true smoking status in the analysis ; and ( 6 ) collecting follow-up data blind to smokers ' allocation to trial group . We believe that these criteria provide the best compromise between practicability and surrogacy for long-term cessation and will enable meaningful comparison between studies . There may be good reasons why other outcome criteria would also be reported , and studies that involve interventions with special groups or where there is no design ated target quit date or face to face contact would need to adapt these criteria accordingly Background Genetic testing for risk of weight gain is already available over the internet despite uncertain benefits and concerns about adverse emotional or behavioral effects . Few studies have assessed the effect of adding genetic test feedback to weight control advice , even though one of the proposed applications of genetic testing is to stimulate preventive action . This study will investigate the motivational effect of adding genetic test feedback to simple weight control advice in a situation where weight gain is relatively common . Methods / design First-year university students ( n = 800 ) will be r and omized to receive either 1 ) their personal genetic test result for a gene ( FTO ) related to weight gain susceptibility in addition to a leaflet with simple weight control advice ( ‘ Feedback + Advice ’ group , FA ) , or 2 )  only the leaflet containing simple weight control advice ( ‘ Advice Only ’ group , AO).Motivation to avoid weight gain and active use of weight control strategies will be assessed one month after receipt of the leaflet with or without genetic test feedback .  Weight and body fat will be measured at baseline and eight months follow-up . We will also assess short-term psychological reactions to the genetic test result . In addition , we will explore interactions between feedback condition and gene test status . Discussion We hope to provide a first indication of the clinical utility of weight-related genetic test feedback in the prevention context .Trial registration Current controlled trials IS RCT 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 OBJECTIVE To examine whether diabetes genetic risk testing and counseling can improve diabetes prevention behaviors . RESEARCH DESIGN AND METHODS We conducted a r and omized trial of diabetes genetic risk counseling among overweight patients at increased phenotypic risk for type 2 diabetes . Participants were r and omly allocated to genetic testing versus no testing . Genetic risk was calculated by summing 36 single nucleotide polymorphisms associated with type 2 diabetes . Participants in the top and bottom score quartiles received individual genetic counseling before being enrolled with untested control participants in a 12-week , vali date d , diabetes prevention program . Middle-risk quartile participants were not studied further . We examined the effect of this genetic counseling intervention on patient self-reported attitudes , program attendance , and weight loss , separately comparing higher-risk and lower-risk result recipients with control participants . RESULTS The 108 participants enrolled in the diabetes prevention program included 42 participants at higher diabetes genetic risk , 32 at lower diabetes genetic risk , and 34 untested control subjects . Mean age was 57.9 ± 10.6 years , 61 % were men , and average BMI was 34.8 kg/m2 , with no differences among r and omization groups . Participants attended 6.8 ± 4.3 group sessions and lost 8.5 ± 10.1 pounds , with 33 of 108 ( 30.6 % ) losing ≥5 % body weight . There were few statistically significant differences in self-reported motivation , program attendance , or mean weight loss when higher-risk recipients and lower-risk recipients were compared with control subjects ( P > 0.05 for all but one comparison ) . CONCLUSIONS Diabetes genetic risk counseling with currently available variants does not significantly alter self-reported motivation or prevention program adherence for overweight individuals at risk for diabetes PURPOSE Markers of genetic susceptibility to tobacco-related cancers could personalize harms of smoking and motivate cessation . Our objective was to assess whether a multicomponent intervention that included feedback about genetic susceptibility to lung cancer increased risk perceptions and rates of smoking cessation compared with a st and ard cessation intervention . EXPERIMENTAL DESIGN Our design was a two-arm trial with eligible smokers r and omized in a 1:2 ratio to Enhanced Usual Care or Biomarker Feedback ( BF ) .  Surveys were conducted at baseline , 6 , and 12 months later . The setting was an inner city community health clinic . African-American patients who were current smokers ( n = 557 ) were identified by chart abstract ion and provider referral . All smokers received a self-help manual and , if appropriate , nicotine patches . Smokers in the BF arm also were offered a blood test for genotyping the GST(3 ) gene ( GSTM1 ) , sent a test result booklet , and called up to four times by a health educator . Prevalent abstinence was assessed by self-report of having smoked no cigarettes in the prior 7 days at the 6- and 12-month follow-ups and sustained abstinence , i.e. , not smoking at either follow-up or in-between . RESULTS Smoking cessation was greater for the BF arm than the Enhanced Usual Care arm ( 19 % versus 10 % , respectively ; P < 0.006 ) at 6 months but not at 12 months . CONCLUSIONS Smokers agreed to genetic feedback as part of a multicomponent cessation program . Although the program increased short-term cessation rates compared with st and ard intervention , genetic feedback of susceptibility may not benefit smokers with high baseline risk perceptions Background Proponents of consumer genetic tests cl aim that the information can positively impact health behaviors and aid in chronic disease prevention . However , the effects of disclosing genetic information on dietary intake behavior are not clear . Methods A double-blinded , parallel group , 2∶1 online r and omized controlled trial was conducted to determine the short- and long-term effects of disclosing nutrition-related genetic information for personalized nutrition on dietary intakes of caffeine , vitamin C , added sugars , and sodium . Participants were healthy men and women aged 20–35 years ( n = 138 ) . The intervention group ( n = 92 ) received personalized DNA-based dietary advice for 12-months and the control group ( n = 46 ) received general dietary recommendations with no genetic information for 12-months .  Food frequency question naires were collected at baseline and 3- and 12-months after the intervention to assess dietary intakes . General linear models were used to compare changes in intakes between those receiving general dietary advice and those receiving DNA-based dietary advice . Results Compared to the control group , no significant changes to dietary intakes of the nutrients were observed at 3-months . At 12-months , participants in the intervention group who possessed a risk version of the ACE gene , and were advised to limit their sodium intake , significantly reduced their sodium intake ( mg/day ) compared to the control group ( −287.3±114.1 vs. 129.8±118.2 , p = 0.008 ) . Those who had the non-risk version of ACE did not significantly change their sodium intake compared to the control group ( 12-months : −244.2±150.2 , p = 0.11 ) . Among those with the risk version of the ACE gene , the proportion who met the targeted recommendation of 1500 mg/day increased from 19 % at baseline to 34 % after 12 months ( p = 0.06 ) . Conclusions These findings demonstrate that disclosing genetic information for personalized nutrition results in greater changes in intake for some dietary components compared to general population -based dietary advice . Trial Registration Clinical Trials.gov Objective To test the hypothesis that adding obesity gene feedback ( FTO ) to simple weight control advice at a life stage with raised risk of weight gain ( university ) increases readiness to control weight . Methods Individually r and omized controlled trial comparing the effect of : ( i ) simple weight control advice plus FTO feedback ( FA ) and ( ii ) simple weight control advice only ( AO ) on readiness to engage with weight control . Differences in stage of change by genotype and differential weight control behaviors were secondary outcomes . Results Of 1,016 participants r and omized , only 279 completed follow-up , yielding 90 % power to detect a small effect for readiness to control weight . As predicted , FA participants were more likely to be in the contemplation stage than AO participants ( P = 0.023 ) . Participants receiving higher-risk genetic results were at a higher stage of change than controls ( P = 0.003 ) , with a trend toward a higher stage of change than those getting lower-risk results ( P = 0.051 ) . Lower-risk results did not decrease weight control intentions compared with controls ( P = 0.55 ) . There were no group differences in adherence to recommended weight control behaviors ( P = 0.87 ) . Conclusions Adding FTO feedback to weight control advice enhanced readiness to control weight , without evidence for genetic determinism , but had no more effect on behavior than weight control advice alone Background We describe the study design , procedures , and development of the risk counseling protocol used in a r and omized controlled trial to evaluate the impact of genetic testing for diabetes mellitus ( DM ) on psychological , health behavior , and clinical outcomes . Methods / Design Eligible patients are aged 21 to 65 years with body mass index ( BMI ) ≥27 kg/m2 and no prior diagnosis of DM . At baseline , conventional DM risk factors are assessed , and blood is drawn for possible genetic testing . Participants are r and omized to receive conventional risk counseling for DM with eye disease counseling or with genetic test results . The counseling protocol was pilot tested to identify an acceptable graphical format for conveying risk estimates and match the length of the eye disease to genetic counseling . Risk estimates are presented with a vertical bar graph denoting risk level with colors and descriptors . After receiving either genetic counseling regarding risk for DM or control counseling on eye disease , brief lifestyle counseling for prevention of DM is provided to all participants . Discussion A st and ardized risk counseling protocol is being used in a r and omized trial of 600 participants . Results of this trial will inform policy about whether risk counseling should include genetic counseling . Trial registration Clinical Trials.gov Identifier PURPOSE This paper describes an ongoing r and omized controlled trial design ed to assess the impact of genetic and environmental risk assessment ( GERA ) on colorectal cancer ( CRC ) screening . METHODS The trial includes asymptomatic patients who are 50 - 79years and are not up-to- date with CRC screening guidelines . Patients who responded to a baseline telephone survey are r and omized to a GERA or Control group .  GERA group participants meet with a nurse , decide whether to have a GERA blood test ( a combination of genetic polymorphism and folate ) , and , if tested , receive GERA feedback . Follow-up telephone surveys are conducted at 1 and 6months . A chart audit is performed at 6months . RESULTS Of 2,223 eligible patients , 562 ( 25 % ) have enrolled . Patients who enrolled in the study were significantly younger than those who did not ( p<0.001 ) . Participants tended to be 50 - 59years ( 64 % ) , female ( 58 % ) , white ( 52 % ) , married ( 51 % ) , and have more than a high school education ( 67 % ) . At baseline , most participants had some knowledge of CRC screening and  GERA , viewed CRC screening favorably , and reported that they had decided to do screening . Almost half had worries and concerns about CRC . CONCLUSIONS One in four eligible primary care patients enrolled in the study . Age was negatively associated with enrollment . Prospect i ve analyses using data for all participants will provide more definitive information on GERA uptake and the impact of GERA feedback This paper explores whether and how the behavioral impact of genotype disclosure can be disentangled from the impact of numerical risk estimates generated by genetic tests . Secondary data analyses are presented from a r and omized controlled trial of 162 first-degree relatives of Alzheimer 's disease ( AD ) patients . Each participant received a lifetime risk estimate of AD . Control group estimates were based on age , gender , family history , and assumed epsilon4-negative apolipoprotein E ( APOE ) genotype ; intervention group estimates were based upon the first three variables plus true APOE genotype , which was also disclosed . AD-specific self-reported behavior change ( diet , exercise , and medication use ) was assessed at 12 months . Behavior change was significantly more likely with increasing risk estimates , and also more likely , but not significantly so , in epsilon4-positive intervention group participants ( 53 % changed behavior ) than in control group participants ( 31 % ) . Intervention group participants receiving epsilon4-negative genotype feedback ( 24 % changed behavior ) and control group participants had similar rates of behavior change and risk estimates , the latter allowing assessment of the independent effects of genotype disclosure . However , collinearity between risk estimates and epsilon4-positive genotypes , which engender high-risk estimates , prevented assessment of the independent effect of the disclosure of an epsilon4 genotype . Novel study design s are proposed to determine whether genotype disclosure has an impact upon behavior beyond that of numerical risk estimates This trial tests the hypothesis that confirming a clinical diagnosis of familial hypercholesterolemia ( FH ) by finding a genetic mutation reduces patients ' perceptions of control over the disease and adherence to risk‐reducing behaviors . Three hundred forty‐one families , comprising 341 hypercholesterolemia prob and s and 128 adult relatives , were r and omized to one of two groups : ( a ) routine clinical diagnosis ; ( b ) routine clinical diagnosis plus genetic testing ( mutation search ing in prob and s and direct gene testing in relatives ) . The main outcome measures were perceptions of control over hypercholesterolemia , adherence to cholesterol‐lowering medication , diet , physical activity , and smoking .  There was no support for the main hypothesis : finding a mutation had no impact on perceived control or adherence to risk‐reducing behavior ( all P‐values > 0.10 ) . While all groups believed that lowering cholesterol was an effective way of reducing the risk of a heart attack , participants in whom a mutation was found believed less strongly in the efficacy of diet in reducing their cholesterol level ( P = 0.02 at 6 months ) and showed a trend in believing more strongly in the efficacy of cholesterol‐lowering medication ( P = 0.06 at 6 months ) . In conclusion , finding a mutation to confirm a clinical diagnosis of FH in a previously aware population does not reduce perceptions of control or adherence to risk‐reducing behaviors . The pattern of findings leads to the new hypothesis that genetic testing does not affect the extent to which people feel they have control over a condition , but does affect their perceptions of how control is most effectively achieved . Further work is needed to determine whether similar results will be obtained in population s with little previous awareness of their risks . © 2004 Wiley‐Liss , Abstract An analogue study investigated the impact of genetic testing on perceptions of disease . Using a 2 × 2 design , participants ( n = 212 ) imagined receiving the information that they were at increased risk for either heart disease or arthritis . The type of risk information was either genetic or unspecified . Presentation of genetic risk information result ed in the condition being perceived as less preventable . Causal models of disease where investigated using principal components analysis . When hem disease was the stimulus condition , attributions to genes and chance were positively associated following unspecified risk information , and negatively associated following genetic risk information . When arthritis was the stimulus condition , presentation of genetic risk information was associated with attributions to genes becoming separated from the other attributions . One explanation for this is that providing genetic risk information  may decrease perceptions of a sense of r and omness or uncertainty in disease causation . The extent to which these effects occur in clinical population s. and their behavioural consequences . needs to be established Objective We examined the clinical utility of supplementing  type 2 diabetes mellitus ( DM )  risk counseling with DM genetic test results and counseling . Research Design and Methods In this r and omized controlled trial , non-diabetic overweight/obese veteran out patients aged 21 to 65 years received DM risk estimates for lifetime risk , family history , and fasting plasma glucose , followed by either genetic test results ( CR+G ; N = 303 ) or control eye disease counseling ( CR+EYE ; N = 298 ) . All participants received brief lifestyle counseling encouraging weight loss to reduce the risk of DM . Results The mean age was 54 years , 53 % of participants were black , and 80 % were men . There was no difference between arms in weight ( estimated mean difference between CR+G vs. CR+EYE at 3 months = 0.2 kg , 95 % CI : −0.3 to 0.7 ; at 6 months = 0.4 kg , 95 % CI : −0.3 to 1.1 ) , insulin resistance , perceived risk , or physical activity at 3 or 6 months . Calorie and fat intake were lower in the CR+G arm at 3 months ( p ’s ≤ 0.05 ) but not at 6 months ( p ’s > 0.20 ) . Conclusions Providing patients with genetic test results was not more effective in changing patient behavior to reduce the risk of DM compared to conventional risk counseling . Trial registration : Clinical Trials.gov NCT01060540 http:// clinical OBJECTIVES It is well-known that smoking causes many diseases including cancers . Informing smokers of their genotypes associated with the vulnerability to the harms of smoking may be effective measures for smoking cessation . The present study examined the effects of genotype notification of an oncogene ( L-myc ) genotype to smokers on their behavior to quit smoking . METHODS Subjects were 562 employees of a bank who answered to be a smoker for a question naire used at annual health checkup at workplace from July to December 2002 . Those enrolled on August , October , and December were allocated into the genotype notification group ( intervention group ) , and the rest into the controls .  Among 286 smokers allocated into the intervention group , 257 participants ( 89.9 % ) agreed to genotype testing . One year after the enrollment , a follow-up question naire survey was conducted for all smokers including controls . RESULTS Those who stated to have quitted smoking were 22 ( 8.0 % ) among the 276 controls and 15 ( 5.8 % ) among the 257 genotype notified participants , providing that the odds ratio ( OR ) of cessation for the intervention was 0.64 ( 95 % confidence interval , 0.32 - 1.28 ) . No psychological problems associated with genotype notification were observed . CONCLUSION The present study did not show positive effects of genotype notification on smoking cessation rate . To elevate the cessation rate , methods to explain and notify genotypes should be improved This article introduces the approach of GRADE to rating  quality of evidence .  GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence Risk information for Alzheimer disease ( AD ) may be communicated through susceptibility gene disclosure , even though this is not currently in clinical use . The REVEAL Study is the first r and omized clinical trial of risk assessment for AD with apolipoprotein E ( APOE ) genotype and numerical risk estimate disclosure . We examined whether APOE genotype and numerical risk disclosure to asymptomatic individuals at high risk for AD alters health behaviors . One hundred sixty-two participants were r and omized to either intervention ( APOE disclosure ) or control ( no genotype disclosure ) groups . Subjects in both groups received numerical lifetime risk estimates of future AD development based on sex and family history of AD . The intervention group received their APOE genotype . Subjects were informed that no proven preventive measures for AD existed and given an information sheet on preventative therapies under investigation . Participants who learned they were ϵ4 positive were significantly more likely than ϵ4 negative participants to report AD-specific health behavior change 1 year after disclosure ( adjusted odds ratio : 2.73 ; 95 % confidence interval : 1.14 , 6.54 ; P=0.02 ) . Post hoc analyses revealed similar significant associations between numerical lifetime risk estimates and self-report of AD-specific health behavior change . Despite lack of preventive measures for AD , knowledge of APOE genotype , numerical lifetime risk , or both , influences health behavior BACKGROUND To evaluate whether feedback of genetic information regarding an L-myc polymorphism , identified as impacting on tobacco-related cancer risk , has an influence on smoking cessation , an intervention study was conducted . METHODS We recruited smokers from first-visit out patients at Aichi Cancer Center Hospital . Six hundred and seventeen participated and were allocated into two groups : the biomarker feedback group ( BF ) and the follow-up smoking status group ( FS ) . The subjects were asked for their smoking status at enrolment and at 3- and 9-month follow-ups . BF subjects were notified about their L-myc genotype . RESULTS The smoking cessation rate at 9-month follow-up was essentially the same for both BF and FS cases , at 18.8 % and 17.0 % , respectively ( P = 0.798 ) . However , a difference in the rate was evident with non-cancer subjects ( 12.7 % and 8.4 % , respectively , P = 0.237 ) , especially in females ( 15.0 % and 4.2 % , respectively , P = 0.024 ) . The non-cancer subjects informed of their genotype were more likely to quit smoking than the FS patients ; particularly in those having a risky genotype , this was significant ( odds ratio : 2.87 , P = 0.003 ) . Again it was most prominent in females . CONCLUSION Feedback regarding an L-myc polymorphism did not impact on smoking cessation overall but appeared to benefit smokers without cancer . In addition , gender could affect the response to the feedback Objective To test the hypothesis that communicating risk of developing Crohn ’s disease based on genotype and that stopping smoking can reduce this risk , motivates behaviour change among smokers at familial risk . Design Parallel group , cluster r and omised controlled trial . Setting Families with Crohn ’s disease in the United Kingdom . Participants 497 smokers ( mean age 42.6 ( SD 14.4 ) years ) who were first degree relatives of prob and s with Crohn ’s disease , with outcomes assessed on 209/251 ( based on DNA analysis ) and 217/246 ( st and ard risk assessment ) . Intervention Communication of risk assessment for Crohn ’s disease by postal booklet based on family history of the disease and smoking status alone , or with additional DNA analysis for the NOD2 genotype . Participants were then telephoned by a National Health Service Stop Smoking counsellor to review the booklet and deliver brief st and ard smoking cessation intervention . Calls were tape recorded and a r and om sub sample selected to assess fidelity to the clinical protocol . Main outcome measure The primary outcome was smoking cessation for 24 hours or longer , assessed at six months . Results The proportion of participants stopping smoking for 24 hours or longer did not differ between arms : 35 % ( 73/209 ) in the DNA arm versus 36 % ( 78/217 ) in the non-DNA arm ( difference −1 % , 95 % confidence interval −10 % to 8 % , P=0.83 ) . The proportion making a quit attempt within the DNA arm did not differ between those who were told they had mutations putting them at increased risk ( 36 % ) , those told they had none ( 35 % ) , and those in the non-DNA arm ( 36 % ) . Conclusion Among relatives of patients with Crohn ’s disease , feedback of DNA based risk assessment s does not motivate behaviour change to reduce risk any more or less than st and ard risk assessment . These findings accord with those across a range of population s and behaviours . They do not support the promulgation of commercial DNA based tests nor the search for gene variants that confer increased risk of common complex diseases on the basis that they effectively motivate health related behaviour change . Trial registration Current Controlled Trials IS RCT N21633644 The behavioural and psychological impact of genetic testing for lung cancer susceptibility was examined among smokers ( N = 61 ) who were r and omly allocated to a GSTM1 genetic testing group ( with GSTM1-missing or GSTM1-present result ) or no-test control group . The GSTM1-missing ( higher risk ) group reported greater motivation to quit smoking , and both genetic testing groups reported lower depression than the control group at one-week follow-up ( p < .05 for all ) . Differences were not significant at two months follow-up . This study indicates the feasibility of much-needed research into the risks and benefits for individuals of emerging lifestyle-related genetic susceptibility tests Encouraging behavioral changes to decrease alcohol intake is not easy from the st and point of health support . This study was conducted to examine whether the genetic diagnosis of ALDH2 polymorphism is useful in supporting those who want to decrease their alcohol intake . The participants in this study were 329 male employees who wanted to know the result of their ALDH2 genotype . We divided the 329 participants r and omly into two groups . One was the " notified group " ( n=157 ) , and the other was the " non-notified group " ( n=172 ) . The subjects belonging to the " notified group " were informed of the results of the ALDH2 genotype diagnosis in April , 2003 . Drinking habits and laboratory data were obtained before and after notification of the ALDH2 genotype . Among those with genotype ALDH2 * 1/*1 , there was no significant change in drinking frequencies , nor was there any significant decline in liver function laboratory data in either of the groups before and after notification of the genotype . However , weekly alcohol intake tended to increase compared to that before notification . On the other h and , with regard to those with genotype ALDH2 * 1/*2 , no significant changes in drinking frequencies or liver function laboratory data were evident in either group before and after notification of the genotype . However , the weekly alcohol intake tended to increase in the non-notified group , whereas it tended to decrease in the notified group . Although the result was not significant , it is suggested that , with further study and an increased sample size , the genetic diagnosis may be found to be useful This study evaluated the long-term impact of genetic susceptibility biomarker feedback on smoking behavior change and symptoms of depression in 426 male and female smokers . Smokers were r and omized to one of three smoking-cessation interventions : minimal contact quit-smoking counseling ( QSC ) , QSC + exposure biomarker feedback ( EBF ) , and QSC + EBF + biomarker feedback about genetic susceptibility to lung cancer ( SBF ) . The logistic regression model for quit attempt revealed a significant main effect for treatment such that participants in the SBF group were more than two times more likely to make a quit attempt than participants in the QSC group . There was not a significant difference between EBF and QSC participants . The results also revealed a significant effect for baseline stage of change . Those smokers in the preparation stage at baseline were more than three times more likely to make a quit attempt over the 12 months following treatment . The models for 30-day cessation and follow-up smoking rate revealed no significant main or interacting effects for treatment . A repeated measures analysis of variance revealed a significant main effect for time , indicating that an initial increase in depression in the genetic susceptibility group was not maintained over time . Genetic susceptibility feedback has the intended effects on motivation to quit , but it may need to be delivered within a more intensive smoking-cessation treatment for the heightened motivation to translate into smoking cessation
OBJECTIVE To assess the impact of communicating DNA based  disease risk  estimates on risk-reducing health behaviours and motivation to engage in such behaviours .