Supplementary Table 1 and 2. Supplementary table 1. Comparison of characteristics of patients included and excluded from the analysis sample. Supplementary table 2. Factors associated with diagnosis with stage III/IV disease (sensitivity analysis for alternative parameterization of stage at diagnosis.)

Introduction/Background Ashkenazi-Jewish (AJ) population-based BRCA-testing is acceptable, does not detrimentally impact psychological well-being or quality of life, is cost-effective and amplifies primary prevention for breast cancer (BC) ovarian cancer (OC). However, prospective data describing lifestyle impact are lacking. We report long-term results of a population-based BRCA-testing randomised controlled trial (RCT) on lifestyle behaviour and cancer-risk perception. Methodology We designed a two-arm RCT (ISRCTN-73338115, GCaPPS): (a)Population-Screening (PS) arm; (b) family-history (FH)/Clinical-criteria testing arm. Women and men >18-years in the North-London AJ-population were offered informed pre-test genetic counselling and BRCA testing. Participants were recruited through self-referral. Exclusions included: prior BRCA-testing or first-degree relatives of BRCA-carriers. The intervention included genetic-testing for three AJ BRCA-mutations: 185delAG(c.68_69delAG), 5382insC(c.5266dupC) and 6174delT(c.5946delT). This was undertaken for all participants in the PS-arm; and participants fulfilling FH/clinical-criteria in the FH-arm. Patients filled customised/validated questionnaires at baseline/1-year/2-years/3-years follow-up. Outcome measures included lifestyle/behavioural outcomes. Generalized linear-mixed models adjusted for covariates and appropriate contrast-tests were used for between-group and within-group analysis of lifestyle and behavioural outcomes along-with evaluating factors associated with these outcomes. Outcomes are adjusted for multiple testing (Bonferoni method), with p<0.0039 considered significant. Results 1034 participants were randomized to PS (n=530) or FH (n=504) arms. No significant difference was identified between PS and FH-based BRCA-testing approaches for dietary fruit/vegetable/meat consumption, vitamin intake, alcohol quantity/frequency, smoking behaviour (frequency/cessation), physical activity/exercise or routine breast mammogram screening behaviour, with outcomes not affected by BRCA test result. Cancer-risk perception decreased with time following BRCA-testing with no difference between FH/PS approaches. The risk was found to be lowest in BRCA-negative participants. Men consume fewer fruits, vegetables and vitamins but more meat and alcohol than women (p<0.001). Conclusion Population-based and FH-based AJ BRCA-testing have similar long-term life-style impacts for smoking, alcohol, dietary fruit/vegetable/meat/vitamin, exercise, breast screening participation and reduced cancer-risk perception.

Ashkenazi‐Jewish (AJ) population‐based BRCA testing is acceptable, cost‐effective and amplifies primary prevention for breast & ovarian cancer. However, data describing lifestyle impact are lacking. We report long‐term results of population‐based BRCA testing on lifestyle behaviour and cancer risk perception.

Background: Primary care is the 'first port of call' for weight control advice, creating a need for simple, effective interventions that can be delivered without specialist skills. Ten Top Tips (10TT) is a leaflet based on habit-formation theory that could fill this gap. The aim of the current study was to test the hypothesis that 10TT can achieve significantly greater weight loss over 3 months than ‘usual care’. Methods: A two-arm, individually randomised, controlled trial in primary care. Adults with obesity were identified from 14 primary care providers across England. Patients were randomised to either 10TT or 'usual care' and followed up at 3, 6, 12, 18 and 24 months. The primary outcome was weight loss at 3 months, assessed by a health professional blinded to group allocation. Difference between arms was assessed using a mixed-effect linear model taking into account the health professionals delivering 10TT, and adjusted for baseline weight. Secondary outcomes included body mass index, waist circumference, the number achieving a 5% weight reduction, clinical markers for potential comorbidities, weight loss over 24 months and basic costs. Results: Five-hundred and thirty-seven participants were randomised to 10TT ( n =267) or to ‘usual care' ( n =270). Data were available for 389 (72%) participants at 3 months and for 312 (58%) at 24 months. Participants receiving 10TT lost significantly more weight over 3 months than those receiving usual care (mean difference =−0.87kg; 95% confidence interval: −1.47 to −0.27; P =0.004). At 24 months, the 10TT group had maintained their weight loss, but the ‘usual care’ group had lost a similar amount. The basic cost of 10TT was low, that is, around £23 ($32) per participant. Conclusions: The 10TT leaflet delivered through primary care is effective in the short-term and a low-cost option over the longer term. It is the first habit-based intervention to be used in a health service setting and offers a low-intensity alternative to ‘usual care’.

Rationale: Low uptake of low-dose computed tomography (LDCT) lung cancer screening, particularly by current smokers of a low socioeconomic position, compromises effectiveness and equity. Objectives: To compare the effect of a targeted, low-burden, and stepped invitation strategy versus control on uptake of hospital-based Lung Health Check appointments offering LDCT screening. Methods: In a two-arm, blinded, between-subjects, randomized controlled trial, 2,012 participants were selected from 16 primary care practices using these criteria: 1) aged 60 to 75 years, 2) recorded as a current smoker within the last 7 years, and 3) no prespecified exclusion criteria contraindicating LDCT screening. Both groups received a stepped sequence of preinvitation, invitation, and reminder letters from their primary care practitioner offering prescheduled appointments. The key manipulation was the accompanying leaflet. The intervention group's leaflet targeted psychological barriers and provided low-burden information, mimicking the concept of the U.K. Ministry of Transport's annual vehicle test ("M.O.T. For Your Lungs"). Measurements and Main Results: Uptake was 52.6%, with no difference between intervention (52.3%) and control (52.9%) groups in unadjusted (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.82-1.16) or adjusted (OR, 0.98; 95% CI, 0.82-1.17) analyses. Current smokers were less likely to attend (adjusted OR, 0.70; 95% CI, 0.56-0.86) than former smokers. Socioeconomic deprivation was significantly associated with lower uptake for the control group only (P <0.01). Conclusions: The intervention did not improve uptake. Regardless of trial arm, uptake was considerably higher than previous clinical and real-world studies, particularly given that the samples were predominantly lower socioeconomic position smokers. Strategies common to both groups, including a Lung Health Check approach, could represent a minimum standard.

Introduction/Background Unselected population-based BRCA-testing enables application of genomics on a population-scale to maximise primary-prevention for breast-&-ovarian cancer. We present factors affecting uptake and long-term follow-up results of the GCaPPS-trial comparing population-based and Family-History (FH)/Clinical-criteria based BRCA-testing. Methodology Design: Randomised-Controlled-Trial (ISRCTN73338115) GCaPPS, with two-arms: (a)Population-Screening (PS); (b)FH/Clinical-criteria based testing. Setting: North-London Ashkenazi-Jewish(AJ) population. Population-based RCT (1:1). Participants recruited through self-referral, from North-London AJ-population. Inclusion-criteria: AJ women/men >18years. Exclusion-criteria: prior BRCA-testing or first-degree-relatives of BRCA-carriers. Interventions: Pre-test counselling for BRCA-testing through recruitment-clinics (clusters). Genetic-testing for Jewish BRCA founder-mutations: 185delAG(c.68_69delAG), 5382insC(c.5266dupC) and 6174delT(c.5946delT), for (a)all participants in PS-arm; (b)those fulfilling FH/clinical-criteria in FH-arm. Validated questionnaires (HADS/MICRA/HAI/SF12) analysed psychological well-being/quality-of-life outcomes at baseline, 1-year, 2-years and 3-years follow-up. Linear mixed-models and appropriate contrast-tests analysed the impact of BRCA-testing on psychological and quality-of-life outcomes over 3-years. Socio-demographic/family-history/knowledge/psychological well-being data along-with benefits/risks/cultural-influences (18-item-questionnaire measuring 'attitude') were collected. Logistic-regression models evaluated factors affecting uptake/interest/intention-to undergo BRCA-testing. Results 1034 (women=691/men=343) participants randomized to PS (n=530) or FH (n=504) arms. There was a statistically significant decrease in anxiety(p=0.046) and total anxiety-&-depression scores(p=0.0.012) in the PS-arm compared to FH-arm over 3years. No significant difference was observed between FH/PS arms for depression, health-anxiety, distress, uncertainty, quality-of-life or experience scores associated with BRCA-testing. 18/30(60%) BRCA-carriers identified did not fulfil BRCA-testing clinical-criteria. The total BRCA-prevalence= 2.9%(CI:1.97%,4.12%) (BRCA1=1.55%(CI:0.89%,2.5%); BRCA2=1.35%(CI:0.74%,2.26%)). The BRCA-testing uptake was 88%. Being married/cohabiting had four-fold higher-odds for BRCA-testing uptake(p=0.009). Reduced uncertainty/reassurance were the most important factors affecting decision-making. Increased importance/concern towards risks/limitations (confidentiality/insurance/emotional-impact/inability to prevent cancer/marriage-ability/ethnic-focus/stigmatization) were significantly associated with lower-odds of undergoing BRCA-testing, discriminating between acceptors and decliners. Conclusion Population-based AJ BRCA-testing has high acceptability, doesn't adversely affect long-term psychological well-being or quality-of-life, decreases anxiety and could identify up-to 150% additional BRCA-carriers. Pre-test counselling increases awareness of disadvantages/limitations of BRCA-testing, influencing final cost-benefit perception and decision-making on undergoing testing. Disclosure IJ and UM have a financial interest in Abcodia, Ltd., a company formed to develop academic and commercial development of biomarkers for screening and risk prediction. IJ is a member of the board of Abcodia Ltd, a Director of Women's Health Specialists Ltd and received consultancy from Beckton Dickinson. RM declares research funding from The Eve Appeal and Cancer Research UK into population testing and from Barts & the London Charity and Rose Trees Trust outside this work, an honorarium for grant review from Israel National Institute for Health Policy Research and honorarium for advisory board membership from Astrazeneca/MSD. RM is supported by an NHS Innovation Accelerator (NIA) Fellowship for population testing. The other authors declare no conflict of interest.

Objective To evaluate factors affecting unselected population‐based BRCA testing in Ashkenazi Jews ( AJ ). Design Cohort‐study set within recruitment to the GCaPPS trial (ISRCTN73338115). Setting North London AJ population. Population or sample Ashkenazi Jews women/men >18 years, recruited through self‐referral. Methods Ashkenazi Jews women/men underwent pre‐test counselling for BRCA testing through recruitment clinics (clusters). Consenting individuals provided blood samples for BRCA testing. Data were collected on socio‐demographic/family history/knowledge/psychological well‐being along with benefits/risks/cultural influences (18‐item questionnaire measuring ‘attitude’). Four‐item Likert‐scales analysed initial ‘interest’ and ‘intention‐to‐test’ pre‐counselling. Uni‐ and multivariable logistic regression models evaluated factors affecting uptake/interest/intention to undergo BRCA testing. Statistical inference was based on cluster robust standard errors and joint Wald tests for significance. Item‐Response Theory and graded‐response models modelled responses to 18‐item questionnaire. Main outcome measures Interest, intention, uptake, attitude towards BRCA testing. Results A total of 935 individuals (women = 67%/men = 33%; mean age = 53.8 ( SD = 15.02) years) underwent pre‐test genetic‐counselling. During the pre‐counselling, 96% expressed interest in and 60% indicated a clear intention to undergo BRCA testing. Subsequently, 88% opted for BRCA testing. BRCA ‐related knowledge ( P = 0.013) and degree‐level education ( P = 0.01) were positively and negatively (respectively) associated with intention‐to‐test. Being married/cohabiting had four‐fold higher odds for BRCA testing uptake ( P = 0.009). Perceived benefits were associated with higher pre‐counselling odds for interest in and intention to undergo BRCA testing. Reduced uncertainty/reassurance were the most important factors contributing to decision‐making. Increased importance/concern towards risks/limitations (confidentiality/insurance/emotional impact/inability to prevent cancer/marriage ability/ethnic focus/stigmatisation) were significantly associated with lower odds of uptake of BRCA testing, and discriminated between acceptors and decliners. Male gender/degree‐level education ( P = 0.001) had weaker correlations, whereas having children showed stronger ( P = 0.005) associations with attitudes towards BRCA testing. Conclusions BRCA testing in the AJ population has high acceptability. Pre‐test counselling increases awareness of disadvantages/limitations of BRCA testing, influencing final cost‐benefit perception and decision‐making on undergoing testing. Tweetable abstract BRCA testing in Ashkenazi Jews has high acceptability and uptake. Pre‐test counselling facilitates informed decision‐making.

Objectives In examining informed choice in cancer screening, we investigated public awareness that some screening programmes aim to prevent cancer, while others seek to detect cancer at an early stage. Methods A population-based survey of adults aged 50–70 in England (n = 1433), including data on demographic characteristics and screening experience. Participants were asked to select the main purpose of cervical, breast, and colorectal cancer screening (both faecal occult blood testing and flexible sigmoidoscopy). Results Across all four screening programmes, most people thought the main aim was to catch cancer early (71–78%). Only 18 and 14% knew that cervical screening and flexible sigmoidoscopy, respectively, are primarily preventive. Knowledge of the preventive aspect of these two programmes was low across the board, with few demographic patterns. By contrast, 78 and 73% of the sample were aware that breast screening and the faecal occult blood test, respectively, predominantly aim to detect cancer early. For these programmes, accurate knowledge was socially graded, lower in ethnic minority groups, and positively associated with previous participation in the programmes. Conclusions Our findings suggest that although awareness of the purpose of early detection screening is high, awareness that screening can prevent cancer is low across all demographic groups. Understanding the purpose of screening is a key aspect of informed choice but despite current communication strategies highlighting these differences, people do not seem to have a nuanced understanding of these differing aims. Our findings may be indicative of a broader public scepticism about the preventability of cancer.

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Background Genetic risk assessment for breast cancer and ovarian cancer (BCOC) is expected to make major inroads into mainstream clinical practice. It is important to evaluate the potential impact on women ahead of its implementation in order to maximise health benefits, as predictive genetic testing without adequate support could lead to adverse psychological and behavioural responses to risk disclosure. Objective To examine anticipated health behaviour changes and perceived control to disclosure of genetic risk for BCOC and establish demographic and person-specific correlates of adverse anticipated responses in a population-based sample of women. Design Cross-sectional quantitative survey study carried out by the UK Office for National Statistics in January and March 2014. Setting Face-to-face computer-assisted interviews conducted by trained researchers in participants’ homes. Participants 837 women randomly chosen from households across the UK identified from the Royal Mail’s Postcode Address File. Outcome measures Anticipated health behaviour change and perceived control to disclosure of BCOC risk. Results In response to a genetic test result, most women (72%) indicated ‘I would try harder to have a healthy lifestyle’, and over half (55%) felt ‘it would give me more control over my life’. These associations were independent of demographic factors or perceived risk of BCOC in Bonferroni-corrected multivariate analyses. However, a minority of women (14%) felt ‘it isn’t worth making lifestyle changes’ and that ‘I would feel less free to make choices in my life’ (16%) in response to BCOC risk disclosure. The former belief was more likely to be held by women who were educated below university degree level (P<0.001) after adjusting for other demographic and person-specific correlates. Conclusion These findings indicate that women in the UK largely anticipate that they would engage in positive health behaviour changes in response to BCOC risk disclosure.

BACKGROUND:Presenting to primary care with potential cancer symptoms is contingent on one's ability to recognize potentially serious symptoms. We investigated differences between smokers and non-smokers in symptoms experienced, awareness and consulting of potential respiratory, head and neck cancer symptoms. METHODS:Smokers and non-smokers aged over 50 from Yorkshire general practice lists were sent a postal questionnaire asking about symptoms, consulting and awareness of cancer symptoms. Data were analysed using STATA14. RESULTS:Response rate after one reminder was 30.5% (1205/3954). Smoking status was associated with experience of cough (p<0.001), breathlessness (p = 0.002) and tiredness (p = 0.004) with smokers (25.8% of population) more likely than never-smokers (53.6% of population) to experience all three symptoms (cough OR = 2.56;95%CI[1.75-3.75], breathlessness OR = 2.39;95%CI[1.43-4.00], tiredness OR = 1.57;95%CI[1.12-2.19]). Smoking status was associated with awareness of breathlessness as a potential cancer symptom (p = 0.035) and consulting for cough (p = 0.011) with smokers less likely to consult than never-smokers (OR = 0.37;95% CI[0.17-0.80]). CONCLUSION:Our findings suggest that current smokers are more likely to experience cough, breathlessness and tiredness, but are less likely to consult for cough than never-smokers. To increase cancer awareness and promote consulting among smokers, innovative interventions improving symptom recognition and empowering smokers to seek help are required.

Cancer screening is a behavior that represents investment in future health. Such investment may depend on how much ‘future’ a person expects.

BackgroundBowel cancer screening reduces cancer-specific mortality. There is a socioeconomic gradient in the uptake of the English NHS Bowel Cancer Screening Programme (BCSP), which may lead to inequalities in cancer outcomes.ObjectiveTo reduce socioeconomic inequalities in uptake of the NHS BCSP’s guaiac faecal occult blood test (gFOBt) without compromising uptake in any socioeconomic group.DesignWorkstream 1 explored psychosocial determinants of non-uptake of gFOBt in focus groups and interviews. Workstream 2 developed and tested four theoretically based interventions: (1) ‘gist’ information, (2) a ‘narrative’ leaflet, (3) ‘general practice endorsement’ (GPE) and (4) an ‘enhanced reminder’ (ER). Workstream 3 comprised four national cluster randomised controlled trials (RCTs) of the cost-effectiveness of each intervention.MethodsInterventions were co-designed with user panels, user tested using interviews and focus groups, and piloted with postal questionnaires. RCTs compared ‘usual care’ (existing NHS BCSP invitations) with usual care plus each intervention. The four trials tested: (1) ‘gist’ leaflet (n = 163,525), (2) ‘narrative’ leaflet (n = 150,417), (3) GPE on the invitation letter (n = 265,434) and (4) ER (n = 168,480). Randomisation was based on day of mailing of the screening invitation. The Index of Multiple Deprivation (IMD) score associated with each individual’s home address was used as the marker of socioeconomic circumstances (SECs). Change in the socioeconomic gradient in uptake (interaction between treatment group and IMD quintile) was the primary outcome. Screening uptake was defined as the return of a gFOBt kit within 18 weeks of the invitation that led to a ‘definitive’ test result of either ‘normal’ (i.e. no further investigation required) or ‘abnormal’ (i.e. requiring referral for further testing). Difference in overall uptake was the secondary outcome.ResultsThe gist and narrative trials showed no effect on the SECs gradient or overall uptake (57.6% and 56.7%, respectively, compared with 57.3% and 58.5%, respectively, for usual care; allp-values > 0.05). GPE showed no effect on the gradient (p = 0.5) but increased overall uptake [58.2% vs. 57.5% in usual care, odds ratio (OR) = 1.07, 95% confidence interval (CI) 1.04 to 1.10;p < 0.0001]. ER showed a significant interaction with SECs (p = 0.005), with a stronger effect in the most deprived IMD quintile (14.1% vs. 13.3% in usual care, OR = 1.11, 95% CI 1.04 to 1.20;p = 0.003) than the least deprived (34.7% vs. 34.9% in usual care OR = 1.00, 95% CI 0.94 to 1.06;p = 0.98), and higher overall uptake (25.8% vs. 25.1% in usual care, OR = 1.07, 95% CI 1.03 to 1.11;p = 0.001). All interventions were inexpensive to provide.LimitationsIn line with NHS policy, the gist and narrative leaflets supplemented rather than replaced existing NHS BCSP information. This may have undermined their effect.ConclusionsEnhanced reminder reduced the gradient and modestly increased overall uptake, whereas GPE increased overall uptake but did not reduce the gradient. Therefore, given their effectiveness and very low cost, the findings suggest that implementation of both by the NHS BCSP would be beneficial. The gist and narrative results highlight the challenge of achieving equitable delivery of the screening offer when all communication is written; the format is universal and informed decision-making mandates extensive medical information.Future workSocioculturally tailored research to promote communication about screening with family and friends should be developed and evaluated.Trial registrationCurrent Controlled Trials ISRCTN74121020.FundingThis project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full inProgramme Grants for Applied Research; Vol. 5, No. 8. See the NIHR Journals Library website for further project information.

Background: There is evidence that birthweight is positively associated with body mass index (BMI) in later life, but it remains unclear whether this is explained by genetic factors or the intrauterine environment. We analysed the association between birthweight and BMI from infancy to adulthood within twin pairs, which provides insights into the role of genetic and environmental individual-specific factors.Methods: This study is based on the data from 27 twin cohorts in 17 countries. The pooled data included 78 642 twin individuals (20 635 monozygotic and 18 686 same-sex dizygotic twin pairs) with information on birthweight and a total of 214 930 BMI measurements at ages ranging from 1 to 49 years. The association between birthweight and BMI was analysed at both the individual and within-pair levels using linear regression analyses.Results: At the individual level, a 1-kg increase in birthweight was linearly associated with up to 0.9 kg/m(2) higher BMI (P < 0.001). Within twin pairs, regression coefficients were generally greater (up to 1.2 kg/m(2) per kg birthweight, P < 0.001) than those from the individual-level analyses. Intra-pair associations between birthweight and later BMI were similar in both zygosity groups and sexes and were lower in adulthood.Conclusions: These findings indicate that environmental factors unique to each individual have an important role in the positive association between birthweight and later BMI, at least until young adulthood.

Uptake of colorectal cancer screening is low in the English NHS Bowel Cancer Screening Programme (BCSP). Participation in screening is strongly associated with socioeconomic status. The aim of this study was to determine whether a supplementary leaflet providing the ‘gist’ of guaiac-based Faecal Occult Blood test (gFOBt) screening for colorectal cancer could reduce the socioeconomic status (SES) gradient in uptake in the English NHS BCSP.