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1.
J Med Genet ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31719169

RESUMO

BACKGROUND: Germline TP53 gene pathogenic variants (pv) cause a very high lifetime risk of developing cancer, almost 100% for women and 75% for men. In the UK, annual MRI breast screening is recommended for female TP53 pv carriers. The SIGNIFY study (Magnetic Resonance Imaging screening in Li Fraumeni syndrome: An exploratory whole body MRI) study reported outcomes of whole-body MRI (WB-MRI) in a cohort of 44 TP53 pv carriers and 44 matched population controls. The results supported the use of a baseline WB-MRI screen in all adult TP53 pv carriers. Here we report the acceptability of WB-MRI screening and effects on psychosocial functioning and health-related quality of life in the short and medium terms. METHODS: Psychosocial and other assessments were carried out at study enrolment, immediately before MRI, before and after MRI results, and at 12, 26 and 52 weeks' follow-up. RESULTS: WB-MRI was found to be acceptable with high levels of satisfaction and low levels of psychological morbidity throughout. Although their mean levels of cancer worry were not high, carriers had significantly more cancer worry at most time-points than controls. They also reported significantly more clinically significant intrusive and avoidant thoughts about cancer than controls at all time-points. There were no clinically significant adverse psychosocial outcomes in either carriers with a history of cancer or in those requiring further investigations. CONCLUSION: WB-MRI screening can be implemented in TP53 pv carriers without adverse psychosocial outcomes in the short and medium terms. A previous cancer diagnosis may predict a better psychosocial outcome. Some carriers seriously underestimate their risk of cancer. Carriers of pv should have access to a clinician to help them develop adaptive strategies to cope with cancer-related concerns and respond to clinically significant depression and/or anxiety.

2.
Br J Gen Pract ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31636127

RESUMO

BACKGROUND: In Australia, evidence-based guidelines recommend that women consider taking selective oestrogen receptor modulators (SERMs) to reduce their risk of breast cancer. In practice, this requires effective methods for communicating the harms and benefits of taking SERMs so women can make an informed choice. AIM: To evaluate how different risk presentations influence women's decisions to consider taking SERMs. DESIGN AND SETTING: Cross-sectional, correlational study of Australian women in general practice. METHOD: Three risk communication formats were developed that included graphics, numbers, and text to explain the reduction in breast cancer risk and risk of side effects for women taking SERMs (raloxifene or tamoxifen). Women aged 40-74 years in two general practices were shown the risk formats using vignettes of hypothetical women at moderate or high risk of breast cancer and asked to choose 'If this was you, would you consider taking a SERM?' Descriptive statistics and predictors (risk format, level of risk, and type of SERM) of choosing SERMs were determined by logistic regression. RESULTS: A total of 288 women were recruited (an 88% response rate) between March and May 2017. The risk formats that showed a government statement and an icon array were associated with a greater likelihood of considering SERMs relative to one that showed a novel expected frequency tree. Risk formats for raloxifene and for the high-risk vignettes were also more strongly associated with choosing to consider SERMs. No associations were found with any patient demographics. CONCLUSION: Specific risk formats may lead to more women considering taking SERMs to reduce breast cancer risk, especially if they are at high risk of the condition. Raloxifene may be a more acceptable SERM to patients.

3.
Fam Cancer ; 18(4): 389-397, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31209717

RESUMO

Before SNP-based risk can be incorporated in colorectal cancer (CRC) screening, the ability of these SNPs to estimate CRC risk for persons with and without a family history of CRC, and the screening implications need to be determined. We estimated the association with CRC of a 45 SNP-based risk using 1181 cases and 999 controls, and its correlation with CRC risk predicted from detailed family history. We estimated the predicted change in the distribution across predefined risk categories, and implications for recommended screening commencement age, from adding SNP-based risk to family history. The inter-quintile risk ratio for colorectal cancer risk of the SNP-based risk was 3.28 (95% CI 2.54-4.22). SNP-based and family history-based risks were not correlated (r = 0.02). For persons with no first-degree relatives with CRC, screening could commence 4 years earlier for women (5 years for men) in the highest quintile of SNP-based risk. For persons with two first-degree relatives with CRC, screening could commence 16 years earlier for men and women in the highest quintile, and 7 years earlier for the lowest quintile. This 45 SNP panel in conjunction with family history, can identify people who could benefit from earlier screening. Risk reclassification by 45 SNPs could inform targeted screening for CRC prevention, particularly in clinical genetics settings when mutations in high-risk genes cannot be identified. Yet to be determined is cost-effectiveness, resources requirements, community, patient and clinician acceptance, and feasibility with potentially ethical, legal and insurance implications.

4.
Trials ; 19(1): 397, 2018 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-30045764

RESUMO

BACKGROUND: Australia and New Zealand have the highest incidence rates of colorectal cancer worldwide. In Australia there is significant unwarranted variation in colorectal cancer screening due to low uptake of the immunochemical faecal occult blood test, poor identification of individuals at increased risk of colorectal cancer, and over-referral of individuals at average risk for colonoscopy. Our pre-trial research has developed a novel Colorectal cancer RISk Prediction (CRISP) tool, which could be used to implement precision screening in primary care. This paper describes the protocol for a phase II multi-site individually randomised controlled trial of the CRISP tool in primary care. METHODS: This trial aims to test whether a standardised consultation using the CRISP tool in general practice (the CRISP intervention) increases risk-appropriate colorectal cancer screening compared to control participants who receive standardised information on cancer prevention. Patients between 50 and 74 years old, attending an appointment with their general practitioner for any reason, will be invited into the trial. A total of 732 participants will be randomised to intervention or control arms using a computer-generated allocation sequence stratified by general practice. The primary outcome (risk-appropriate screening at 12 months) will be measured using baseline data for colorectal cancer risk and objective health service data to measure screening behaviour. Secondary outcomes will include participant cancer risk perception, anxiety, cancer worry, screening intentions and health service utilisation measured at 1, 6 and 12 months post randomisation. DISCUSSION: This trial tests a systematic approach to implementing risk-stratified colorectal cancer screening in primary care, based on an individual's absolute risk, using a state-of-the-art risk assessment tool. Trial results will be reported in 2020. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry, ACTRN12616001573448p . Registered on 14 November 2016.

5.
BJU Int ; 2018 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-29802810

RESUMO

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening.

7.
Br J Cancer ; 118(2): 266-276, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29301143

RESUMO

BACKGROUND: Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort. METHODS: PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV. RESULTS: 1634 participants had ⩾3 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml-l, PSAV was not significantly associated with presence of cancer or high-grade disease. PSAV did not add to PSA for predicting time to an elevated PSA. When comparing BRCA1/2 carriers to non-carriers, we found a significant interaction between BRCA status and last PSA before biopsy (P=0.031) and BRCA2 status and PSAV (P=0.024). However, PSAV was not predictive of biopsy outcome in BRCA2 carriers. CONCLUSIONS: PSA is more strongly predictive of PrCa in BRCA carriers than non-carriers. We did not find evidence that PSAV aids decision-making for BRCA carriers over absolute PSA value alone.

8.
Fam Cancer ; 16(3): 433-440, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28091804

RESUMO

In the United Kingdom, current screening guidelines for TP53 germline mutation carriers solely recommends annual breast MRI, despite the wide spectrum of malignancies typically seen in this group. This study sought to investigate the role of one-off non-contrast whole-body MRI (WB MRI) in the screening of asymptomatic TP53 mutation carriers. 44 TP53 mutation carriers and 44 population controls were recruited. Scans were read by radiologists blinded to participant carrier status. The incidence of malignancies diagnosed in TP53 mutation carriers against general population controls was calculated. The incidences of non-malignant relevant disease and irrelevant disease were measured, as well as the number of investigations required to determine relevance of findings. In TP53 mutation carriers, 6 of 44 (13.6, 95% CI 5.2-27.4%) participants were diagnosed with cancer during the study, all of which would be considered life threatening if untreated. Two were found to have two primary cancers. Two participants with cancer had abnormalities on the MRI which were initially thought to be benign (a pericardial cyst and a uterine fibroid) but transpired to be sarcomas. No controls were diagnosed with cancer. Fifteen carriers (34.1, 95% CI 20.5-49.9%) and seven controls (15.9, 95% CI 6.7-30.1%) underwent further investigations following the WB MRI for abnormalities that transpired to be benign (p = 0.049). The cancer detection rate in this group justifies a minimum baseline non-contrast WB MRI in germline TP53 mutation carriers. This should be adopted into national guidelines for management of adult TP53 mutation carriers in addition to the current practice of contrast enhanced breast MRI imaging.


Assuntos
Detecção Precoce de Câncer/métodos , Neoplasias/diagnóstico , Neoplasias/genética , Proteína Supressora de Tumor p53/genética , Adulto , Feminino , Predisposição Genética para Doença/genética , Heterozigoto , Humanos , Incidência , Imagem por Ressonância Magnética , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Mutação , Neoplasias/epidemiologia , Reino Unido , Imagem Corporal Total/métodos , Adulto Jovem
9.
Oncologist ; 21(6): 716-22, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27151655

RESUMO

BACKGROUND: A better assessment of individualized prostate cancer (PrCa) risk is needed to improve screening. The use of the prostate-specific antigen (PSA) level for screening in the general population has limitations and is not currently advocated. Approximately 100 common single nucleotide polymorphisms (SNPs) have been identified that are associated with the risk of developing PrCa. The PROFILE pilot study explored the feasibility of using SNP profiling in men with a family history (FH) of PrCa to investigate the probability of detecting PrCa at prostate biopsy (PB). The primary aim of this pilot study was to determine the safety and feasibility of PrCa screening using transrectal ultrasound-guided PB with or without diffusion-weighted magnetic resonance imaging (DW-MRI) in men with a FH. A secondary aim was to evaluate the potential use of SNP profiling as a screening tool in this population. PATIENTS AND METHODS: A total of 100 men aged 40-69 years with a FH of PrCa underwent PB, regardless of their baseline PSA level. Polygenic risk scores (PRSs) were calculated for each participant using 71 common PrCa susceptibility alleles. We treated the disease outcome at PB as the outcome variable and evaluated its associations with the PRS, PSA level, and DW-MRI findings using univariate logistic regression. RESULTS: Of the 100 men, 25 were diagnosed with PrCa, of whom 12 (48%) had clinically significant disease. Four adverse events occurred and no deaths. The PSA level and age at study entry were associated with PrCa at PB (p = .00037 and p = .00004, respectively). CONCLUSION: The results of the present pilot study have demonstrated that PB is a feasible and safe method of PrCa screening in men with a FH, with a high proportion of PrCa identified requiring radical treatment. It is feasible to collect data on PrCa-risk SNPs to evaluate their combined effect as a potential screening tool. A larger prospective study powered to detect statistical associations is in progress. IMPLICATIONS FOR PRACTICE: Prostate biopsy is a feasible and safe approach to prostate cancer screening in men with a family history and detects a high proportion of prostate cancer that needs radical treatment. Calculating a polygenic risk score using prostate cancer risk single nucleotide polymorphisms could be a potential future screening tool for prostate cancer.


Assuntos
Biópsia , Detecção Precoce de Câncer , Polimorfismo de Nucleotídeo Único , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Adulto , Idoso , Estudos Transversais , Imagem de Difusão por Ressonância Magnética , Estudos de Viabilidade , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Antígeno Prostático Específico/análise , Neoplasias da Próstata/diagnóstico por imagem
10.
Epilepsia ; 56(10): 1534-41, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26332423

RESUMO

OBJECTIVE: Up to half of patients assessed for suspected new-onset epileptic seizures report previous undiagnosed events. This suggests that delay to timely and expert assessment is a major issue. Very little is known about the degree of delay or nature of the undiagnosed events, impacting on our understanding of new-onset epilepsy. In this study we aimed to examine events that occur before presentation, as well as the extent and risk factors for delay to assessment. METHOD: Included in this retrospective study were 220 patients diagnosed at the First Seizure Clinic (Austin Health, Australia) between 2003 and 2006 with an epileptic index seizure. Patients with a prior diagnosis of epileptic seizures were excluded. Chart review was undertaken, including detailed interviews conducted by an epileptologist at first assessment. Logistic regression assessed risk factors for delay from first event to presentation, including event characteristics, socioeconomic disadvantage, employment, and distance to medical facility. RESULTS: Forty-one percent (n = 90) of patients had one or more event before their index seizure. Of these, 50% had multiple or more than five prior events and 28% experienced one or more convulsive event before the index seizure. Of the total 220 patients, 36% had delayed presentation >4 weeks, 21% delayed >6 months, and 14% delayed >2 years. First events without convulsions or features likely to disrupt behaviour were strongly associated with delay (p = <0.001). Relative socioeconomic disadvantage was also associated with delay to presentation (p = 0.04). SIGNIFICANCE: Our findings suggest a gap in early diagnosis and care in a sizable proportion of new-onset cases, despite a "first world" urban environment and the availability of free basic medical care. Delay appears particularly likely when events are nonconvulsive or low-impact, suggesting that these seizure types may be underrepresented in studies of new-onset epilepsy. This has implications for our understanding of the incidence, evolution, impact, and treatment response of new-onset epilepsy.


Assuntos
Epilepsia/diagnóstico , Epilepsia/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Epilepsia/fisiopatologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Convulsões/etiologia , Adulto Jovem
11.
Fam Cancer ; 13(2): 197-203, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24389956

RESUMO

The aim of this study was to determine whether BRCA1 and BRCA2 mutation carriers have different baseline CA125 levels compared with non-carriers, and whether a significant difference in pre- and post-operative CA125 levels exists in BRCA mutation carriers undergoing risk-reducing bilateral salpingo-oophorectomy (RRBSO). The study also considered whether CA125 measurements should continue in unaffected BRCA mutation carriers after RRBSO. 383 Eligible women were identified through retrospective review of the BRCA Carrier Clinic at The Royal Marsden NHS Foundation Trust, London, UK. These women all had CA125 levels measured as they were either a carrier or at risk of a BRCA1 or BRCA2 mutation. Of these, 76 went on to have a negative predictive test for their familial mutation and so are classed as 'non-carriers'. 133 BRCA1 and 87 BRCA2 carriers had RRBSO, with a further 26 BRCA1 carriers, 28 BRCA2 carriers and one non-carrier developing ovarian cancer. The remaining 21 BRCA1 and 28 BRCA2 carriers did not have RRBSO or develop ovarian cancer in the time of study follow-up. CA125 levels were measured as surveillance or as part of pre-RRBSO care. CA125 measurement post-RRBSO was continued in 48 BRCA1 and 40 BRCA2 carriers. In 154 BRCA1 mutation carriers, the median baseline (i.e. before RRBSO and with no clinical signs of ovarian cancer) CA125 level was 9.0 U/ml (range 2-78) and was 10.0 U/ml (range 1-43) in 115 BRCA2 mutation carriers. When compared with the 75 non-carriers (median baseline CA125 10.0 U/ml; range 2-52), there was no significant difference between the BRCA1, BRCA2 and non-carrier groups. There was a significant reduction in CA125 from pre- to post-RRBSO in 48 BRCA1 carriers (p = 0.04) but no significant difference in 40 BRCA2 mutation carriers (p = 0.5). Out of a total of 220 mutation carriers who underwent RRBSO, two had an incidental ovarian cancer found on histopathology and another developed primary peritoneal cancer during the follow-up period. Our study is the first to compare initial serum CA125 levels in BRCA1 and BRCA2 mutation carriers with those of non-carriers. Our study found no significant difference between the three groups. A drop in CA125 levels after RRBSO in BRCA1 carriers supports the finding of earlier studies, but differed in that the fall was not seen in BRCA2 carriers. The finding of only one case of post-operative peritoneal cancer in 220 carriers undergoing RRBSO supports the discontinuation of post-RRBSO serum CA125 monitoring in BRCA mutation carriers.


Assuntos
Antígeno Ca-125/sangue , Neoplasias das Tubas Uterinas/sangue , Genes BRCA1 , Genes BRCA2 , Neoplasias Ovarianas/sangue , Adulto , Idoso , Neoplasias das Tubas Uterinas/genética , Neoplasias das Tubas Uterinas/prevenção & controle , Neoplasias das Tubas Uterinas/cirurgia , Feminino , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Mutação , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/prevenção & controle , Neoplasias Ovarianas/cirurgia , Ovariectomia , Vigilância da População , Estudos Retrospectivos , Salpingectomia , Adulto Jovem
12.
Am J Med Genet A ; 158A(3): 559-66, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22315203

RESUMO

We examined factors and experiences associated with parents' use or non-use of genetic counseling services within 5 years of the diagnosis of a birth defect in their child. Eligible parents were identified using birth defects data for births in 2004 in Victoria, Australia, and invited to complete a written questionnaire and optional telephone interview. Participants were asked about sources of genetic information, experiences and satisfaction with obtaining this information, and impressions of genetic services. Reasons given for not attending genetic counseling services included not knowing the service was available, or not feeling a need to attend. Non-users commonly stated they would not consider termination of pregnancy for the type of birth defect experienced or that they obtained information from other sources, such as pediatricians. This study indicates that parents, whose child has been diagnosed with a birth defect, could benefit from being informed about available genetic counseling services. The results show that some non-users of genetics services may have misconceptions about the purpose of genetic counseling and correcting these may increase utilization. This is important in order to ensure all parents receive sufficient information and support after diagnosis of a birth defect in their child.


Assuntos
Anormalidades Congênitas/diagnóstico , Aconselhamento Genético/estatística & dados numéricos , Anormalidades Congênitas/genética , Humanos , Satisfação do Paciente , Encaminhamento e Consulta , Inquéritos e Questionários , Vitória
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