Germline Mutations in CIDEB and Protection against Liver Disease.

BACKGROUND: Exome sequencing in hundreds of thousands of persons may enable the identification of rare protein-coding genetic variants associated with protection from human diseases like liver cirrhosis, providing a strategy for the discovery of new therapeutic targets. METHODS: We performed a multistage exome sequencing and genetic association analysis to identify genes in which rare protein-coding variants were associated with liver phenotypes. We conducted in vitro experiments to further characterize associations. RESULTS: The multistage analysis involved 542,904 persons with available data on liver aminotransferase levels, 24,944 patients with various types of liver disease, and 490,636 controls without liver disease. We found that rare coding variants in APOB, ABCB4, SLC30A10, and TM6SF2 were associated with increased aminotransferase levels and an increased risk of liver disease. We also found that variants in CIDEB, which encodes a structural protein found in hepatic lipid droplets, had a protective effect. The burden of rare predicted loss-of-function variants plus missense variants in CIDEB (combined carrier frequency, 0.7%) was associated with decreased alanine aminotransferase levels (beta per allele, -1.24 U per liter; 95% confidence interval [CI], -1.66 to -0.83; P = 4.8×10-9) and with 33% lower odds of liver disease of any cause (odds ratio per allele, 0.67; 95% CI, 0.57 to 0.79; P = 9.9×10-7). Rare coding variants in CIDEB were associated with a decreased risk of liver disease across different underlying causes and different degrees of severity, including cirrhosis of any cause (odds ratio per allele, 0.50; 95% CI, 0.36 to 0.70). Among 3599 patients who had undergone bariatric surgery, rare coding variants in CIDEB were associated with a decreased nonalcoholic fatty liver disease activity score (beta per allele in score units, -0.98; 95% CI, -1.54 to -0.41 [scores range from 0 to 8, with higher scores indicating more severe disease]). In human hepatoma cell lines challenged with oleate, CIDEB small interfering RNA knockdown prevented the buildup of large lipid droplets. CONCLUSIONS: Rare germline mutations in CIDEB conferred substantial protection from liver disease. (Funded by Regeneron Pharmaceuticals.).

Hereditary Cancer Risk Using a Genetic Chatbot Before Routine Care Visits.

OBJECTIVE: To examine user uptake and experience with a clinical chatbot that automates hereditary cancer risk triage by collecting personal and family cancer history in routine women's health care settings. METHODS: We conducted a multicenter, retrospective observational study of patients who used a web-based chatbot before routine care appointments to assess their risk for hereditary breast and ovarian cancer, Lynch syndrome, and adenomatous polyposis syndromes. Outcome measures included uptake and completion of the risk-assessment and educational section of the chatbot interaction and identification of hereditary cancer risk as evaluated against National Comprehensive Cancer Network criteria. RESULTS: Of the 95,166 patients invited, 61,070 (64.2%) engaged with the clinical chatbot. The vast majority completed the cancer risk assessment (89.4%), and most completed the genetic testing education section (71.4%), indicating high acceptability among those who opted to engage. The mean duration of use was 15.4 minutes (SD 2 hours, 56.2 minutes) when gaps of inactivity longer than 5 minutes were excluded. A personal history of cancer was reported by 19.1% (10,849/56,656) and a family history of cancer was reported by 66.7% (36,469/54,652) of patients who provided the relevant information. One in four patients (14,850/54,547) screened with the chatbot before routine care appointments met National Comprehensive Cancer Network criteria for genetic testing. Among those who were tested, 5.6% (73/1,313) had a disease-causing pathogenic variant. CONCLUSION: A chatbot digital health tool can help identify patients at high risk for hereditary cancer syndromes before routine care appointments. This scalable intervention can effectively provide cancer risk assessment, engage patients with educational information, and facilitate a path toward preventive genetic testing. FUNDING SOURCE: Implementation of the chatbot in clinics was funded by industry support from commercial genetic testing laboratories Ambry, Invitae, and Progenity.

Protective Effects of Statin Therapy in Cirrhosis Are Limited by a Common SLCO1B1 Transporter Variant.

Complications of cirrhosis and portal hypertension (PH) can be reduced by statin therapy. The common loss-of-function variant p.V174A in the solute carrier organic anion transporter gene 1B1 (SLCO1B1) gene encoding the organic anion transporting polypeptide 1B1 results in decreased hepatic uptake of statins. Our specific aim was to assess the impact of this variant in patients with cirrhosis and statin treatment while controlling for the stage of cirrhosis and other potential confounders with propensity score matching (PSM), availing of a large cohort of genotyped study patients. In total, from 1,088 patients with cirrhosis in two German academic medical centers, PSM yielded 154 patients taking statins and 154 matched controls. The effect on PH was assessed by the liver stiffness-spleen size-to-platelet score (LSPS), and complications of cirrhosis were retrospectively recorded applying consensus criteria. As hypothesized, patients on statin treatment presented less frequently with signs of PH: Esophageal varices (41% vs. 62%; P < 0.001) were less common, and LSPS (4.8 ± 11.5 vs. 5.6 ± 6.4; P = 0.01) was reduced. Correspondingly, decompensation events were also reduced in patients on statins (odds ratio [OR] = 0.54, 95% confidence interval [CI] 0.32-0.90; P = 0.02). When the variant in SLCO1B1 was present in patients on statins, esophageal varices (OR = 2.68, 95% CI 1.24-5.81; P = 0.01) and bacterial infections (OR = 2.50, 95% CI 1.14-5.47; P = 0.02) were more common as compared with wild type carriers on statins. Conclusion: In this cohort, signs and complications of PH were reduced in patients with cirrhosis treated with statins. Notably, this effect was diminished by the common loss-of-function variant in SLCO1B1. Further prospective studies in independent cohorts are warranted to confirm these genotype-specific observations.

Healthful plant-based dietary patterns, genetic risk of obesity, and cardiovascular risk in the UK biobank study.

BACKGROUND & AIMS: People with a higher genetic risk for obesity are more likely to develop cardiovascular disease (CVD), and healthy plant-based dietary patterns may be associated with decreased risks of obesity and cardiovascular events. We investigated whether adherence to healthy plant-foods-rich dietary patterns might attenuate risks of obesity and related cardiovascular abnormalities for people at genetically higher risk of obesity. METHODS: This study included 121,799 middle-aged adults in UK Biobank who were initially free of metabolic diseases and cancer. We calculated a healthful plant-based diet index (hPDI) based on 17 major food groups as well as a genetic risk score (GRS) for obesity consisting of body mass index (BMI)-associated variants. The incidence of cardiovascular events (myocardial infarction, MI, or stroke) was prospectively followed during a mean (SD) 5.1 (0.9) years. RESULTS: We found significant interactions between GRS and hPDI on adiposity (Pinteraction <0.0001); adherence to hPDI was more strongly associated with lower levels of adiposity among participants with higher GRS than those with lower GRS. Further, we found a similar pattern of GRS-hPDI interactions on untreated hypertension (Pinteraction = 0.0036). When we tested GRS-hPDI interactions on cardiovascular events, adherence to hPDI was more strongly associated with a decreased risk of MI among people with high GRS (above median) than those with low GRS (Pinteraction = 0.006). Among participants with high GRS, high adherence to hPDI (the top tertile of hPDI) was associated with an HR 0.54 (95% CI: 0.39, 0.74) for MI, as compared to low adherence. CONCLUSIONS: Adherence to healthy plant-based dietary patterns significantly attenuated risks of cardiovascular abnormalities for people at genetically higher risk of obesity. Our results support the precision medicine strategies considering genetics and dietary habits to modify cardiovascular health for people at higher risk of genetically determined obesity.

Precision Nutrition for Alzheimer's Prevention in ApoE4 Carriers.

The ApoE4 allele is the most well-studied genetic risk factor for Alzheimer's disease, a condition that is increasing in prevalence and remains without a cure. Precision nutrition targeting metabolic pathways altered by ApoE4 provides a tool for the potential prevention of disease. However, no long-term human studies have been conducted to determine effective nutritional protocols for the prevention of Alzheimer's disease in ApoE4 carriers. This may be because relatively little is yet known about the precise mechanisms by which the genetic variant confers an increased risk of dementia. Fortunately, recent research is beginning to shine a spotlight on these mechanisms. These new data open up the opportunity for speculation as to how carriers might ameliorate risk through lifestyle and nutrition. Herein, we review recent discoveries about how ApoE4 differentially impacts microglia and inflammatory pathways, astrocytes and lipid metabolism, pericytes and blood-brain barrier integrity, and insulin resistance and glucose metabolism. We use these data as a basis to speculate a precision nutrition approach for ApoE4 carriers, including a low-glycemic index diet with a ketogenic option, specific Mediterranean-style food choices, and a panel of seven nutritional supplements. Where possible, we integrate basic scientific mechanisms with human observational studies to create a more complete and convincing rationale for this precision nutrition approach. Until recent research discoveries can be translated into long-term human studies, a mechanism-informed practical clinical approach may be useful for clinicians and patients with ApoE4 to adopt a lifestyle and nutrition plan geared towards Alzheimer's risk reduction.

Contralateral prophylactic mastectomy: A narrative review of the evidence and acceptability.

The uptake of contralateral prophylactic mastectomy (CPM) has increased steadily over the last twenty years in women of all age groups and breast cancer stages. Since contralateral breast cancer is relatively rare and the breast cancer guidelines only recommend CPM in a small subset of patients with breast cancer, the drivers of this trend are unknown. This review aims to evaluate the evidence for and acceptability of CPM, data on patient rationales for choosing CPM, and some of the factors that might impact patient preferences. Based on the evidence, future recommendations will be provided. First, data on contralateral breast cancer risk and CPM rates and trends are addressed. After that, the evidence is structured around four main patient rationales for CPM formulated as questions that patients might ask their surgeon: Will CPM reduce mortality risk? Will CPM reduce the risk of contralateral breast cancer? Can I avoid future screening with CPM? Will I have better breast symmetry after CPM? Also, three different guidelines regarding CPM will be reviewed. Studies indicate a large gap between patient preferences for radical risk reduction with CPM and the current approaches recommended by important guidelines. We suggest a strategy including shared decision-making to enhance surgeons' communication with patients about contralateral breast cancer and treatment options, to empower patients in order to optimize the use of CPM incorporating accurate risk assessment and individual patient preferences.

Finding the five-year window: A qualitative study examining young women's decision-making and experience of using tamoxifen to reduce BRCA1/2 breast cancer risk.

OBJECTIVE: Tamoxifen has been demonstrated to reduce breast cancer risk in high-risk, premenopausal women. Yet, very few young women with hereditary breast and ovarian cancer syndrome in Australia use tamoxifen, despite this being a less-invasive option compared to risk-reducing mastectomy. This study aims to examine young women's decision-making about and experience of taking tamoxifen to reduce their breast cancer risk. METHODS: Young women with a BRCA1/2 mutation participated in semi-structured qualitative interviews, recruited mainly from a metropolitan clinical genetics service. Data were analysed using an inductive, team-based approach to thematic analysis. RESULTS: Forty interviews with women aged 20-40 years with a BRCA1/2 mutation were conducted. Eleven women could not recall discussing tamoxifen with their healthcare provider or were too young to commence cancer risk management. Twenty-three women chose not to use tamoxifen because it is contraindicated for pregnancy or because it did not offer immediate and great enough risk reduction compared to bilateral risk-reducing mastectomy. Six women who were definite about not wanting to have children during the following 5-year period chose to use tamoxifen, and most experienced none or transient side effects. CONCLUSIONS: Decision-making about tamoxifen was nuanced and informed by considerations characteristic of young adulthood, especially childbearing. Therefore, clinical discussions about tamoxifen with young women with a BRCA1/2 mutation must include consideration of their reproductive plans.

Gestational high fat diet protects 3xTg offspring from memory impairments, synaptic dysfunction, and brain pathology.

Maternal history for sporadic Alzheimer's disease (AD) predisposes the offspring to the disease later in life. However, the mechanisms behind this phenomenon are still unknown. Lifestyle and nutrition can directly modulate susceptibility to AD. Herein we investigated whether gestational high fat diet influences the offspring susceptibility to AD later in life. Triple transgenic dams were administered high fat diet or regular chow throughout 3 weeks gestation. Offspring were fed regular chow throughout their life and tested for spatial learning and memory, brain amyloidosis, tau pathology, and synaptic function. Gestational high fat diet attenuated memory decline, synaptic dysfunction, amyloid-ß and tau neuropathology in the offspring by transcriptional regulation of BACE-1, CDK5, and tau gene expression via the upregulation of FOXP2 repressor. Gestational high fat diet protects offspring against the development of the AD phenotype. In utero dietary intervention could be implemented as preventative strategy against AD.

An Update on Screening and Prevention for Breast and Gynecological Cancers in Average and High Risk Individuals.

Breast and gynecological cancers affect almost 900,000 women and therefore most health care providers will be involved at some point in the management of women with cancer. As the prognosis of all cancers is much more favorable when diagnosed in early stages, it is imperative that all health care providers are familiar not only with current screening guidelines for the average population, but also with the identification of high risk individuals who may benefit from more intense screening as well as available interventions to prevent disease or decrease risk. The purpose of this review article is to provide relevant information to physicians and other health care providers to aid in identifying patients that are classified as "high risk" for developing breast or a gynecologic cancer, outlining what interventions exist for adequate screening and risk reduction strategies, and to provide an update on current screening guidelines for individuals at average and high risk.

Cribado en pacientes con riesgo incrementado de cáncer de mama (parte 1). Pros y contras del cribado con resonancia magnética / Screening in patients with increased risk of breast cancer (part 1): pros and cons of MRI screening

En mujeres con alto riesgo de padecer cáncer de mama, la detección precoz tiene un importante papel. Debido a la alta incidencia de cáncer mamario y a edades más tempranas que en la población general, se recomienda que el cribado comience en edad más joven, y existe amplia evidencia de que la resonancia magnética es la herramienta diagnóstica más sensible: las principales guías americanas y europeas coinciden en la recomendación de realizar resonancia magnética anual (con mamografía anual suplementaria) como modalidad óptima de cribado. No obstante, no hay un total consenso actual entre las guías sobre algunos subgrupos de pacientes a incluir en la recomendación de cribado con resonancia magnética. El objetivo de esta primera parte de nuestro trabajo es, mediante una revisión de la bibliografía, explicar y valorar las ventajas que este tipo de cribado con resonancia magnética proporciona respecto al cribado solo con mamografía, como son: mayor detección de cánceres de menor tamaño y con menor afectación ganglionar asociada y una reducción de los cánceres de intervalo, lo que puede tener repercusión en supervivencia y mortalidad, con efectos comparables a otras medidas de prevención. Pero, a su vez, también queremos reflejar los inconvenientes que el cribado con resonancia magnética conlleva, y que dificultan su aplicabilidad

Screening plays an important role in women with a high risk of breast cancer. Given this population's high incidence of breast cancer and younger age of onset compared to the general population, it is recommended that screening starts earlier. There is ample evidence that magnetic resonance imaging (MRI) is the most sensitive diagnostic tool, and American and the European guidelines both recommend annual MRI screening (with supplementary annual mammography) as the optimum screening modality. Nevertheless, the current guidelines do not totally agree about the recommendations for MRI screening in some subgroups of patients. The first part of this article on screening in women with increased risk of breast cancer reviews the literature to explain and evaluate the advantages of MRI screening compared to screening with mammography alone: increased detection of smaller cancers with less associated lymph node involvement and a reduction in the rate of interval cancers, which can have an impact on survival and mortality (with comparable effects to other preventative measures). At the same time, however, we would like to reflect on the drawbacks of MRI screening that affect its applicability

[Sudden death in the young: the importance of autopsy and DNA testing]. / Plotse dood bij jonge mensen.

When a young person suddenly dies, there is a real chance that this was caused by genetic heart disease. Autopsy plays an important role in determining the cause of death, but the autopsy rate in the Netherlands is relatively low. Practical problems and a lack of information on autopsy play a role. It is important to inform the family on the importance of autopsy and DNA testing. If the family refuses autopsy, consent can be given for removal of material for DNA testing. If no autopsy and no DNA test were done, cardiological screening of family members remains highly recommended. New guidelines and procedures for diagnostics after sudden death are very important. For that reason, we developed a step-by-step plan to support healthcare providers. Early detection of genetic heart disease may prevent sudden death of family members, for example, by using preventive medication or internal defibrillators (ICD).

"It wasn't just for me": Motivations and implications of genetic testing for women at a low risk of hereditary breast and ovarian cancer syndrome.

OBJECTIVE: Genetic testing for hereditary breast and ovarian cancer (HBOC) due to pathogenic variants in BRCA1 or BRCA2 is why most women present to familial cancer centers. Despite being assessed as low risk for HBOC, many women proceed with genetic testing. This study explored the genetic testing experiences of unaffected women at low risk of HBOC to clarify what motivates these women to have testing, and what are the implications of the results. METHODS: A qualitative approach was taken. Participants included women who had genetic testing for HBOC from 2016-2018 at the Parkville Familial Cancer Centre in Melbourne, Australia. In-depth, semi-structured interviews were conducted, and thematic analysis was undertaken on transcripts; transcripts were coded, codes were organized into a hierarchical system of categories/subcategories, and key themes were identified. RESULTS: Analysis of 19 transcripts identified five themes: family underpinned all motivators for HBOC genetic testing; health professionals were influential throughout the process; participants were planning for a positive result; results influenced screening-anxiety and frequency; and negative results gave participants relief in many different ways. The three participants with positive results reported feeling shocked at the results and empowered giving this information to family members. CONCLUSIONS: Women at low HBOC risk may be motivated to seek genetic testing, and access to this is increasingly offered through non-genetic health professionals. Professionals can support clients through genetic testing by recognizing familial experiences, providing accurate information, addressing risk perceptions, and understanding cancer anxiety felt by many women.

Evaluación de riesgo de cáncer en personas expuestas ocupacionalmente a solventes orgánicos / Cancer risk evaluation in individuals occupationally exposed to organic solvents

RESUMEN Objetivo Evaluar la frecuencia de micronúcleos (MN) e influencia de los polimorfismos en los genes del metabolismo GSTM1 y GSTT1 como biomarcadores de riesgo de cáncer en pintores de carros (n=152) con respecto a individuos no expuestos (n=152). Métodos Estudio Epidemiológico Molecular, tipo Corte Transversal analítico, interacción gen-ambiente. La evaluación de MNs y polimorfismos genéticos se determinó con pruebas moleculares en linfocitos de los individuos objeto de estudio. Resultados Se determinó que la frecuencia de MNs es 1.6 más alta en el grupo expuesto con relación al grupo referente (1.39±0.92 versus 0,87±0.78, p<0,0001). No se determinó un incremento en la frecuencia de MNs asociado a los polimorfismos en GSTM1 y GSTT1. Conclusiones El incremento de MNs en pintores de carros sirve para alertar al incremento de riesgo de cáncer en esta población expuesta a solventes orgánicos. Estos resultados pueden servir en Programas de Vigilancia Epidemiológica Ocupacional, como estrategia de prevención y en otros países con un amplio sector informal de individuos expuestos a estos químicos para reducir el riesgo de cáncer.(AU)

ABSTRACT Objective To evaluate the frequency of micronuclei (MNs) and influence of GSTM1 and GSTT1 gene polymorphisms as biomarkers of cancer risk in car painters (n=152) compared to unexposed individuals (n=152). Methods Molecular epidemiology study, cross-sectional analysis of gen and environment interaction. The evaluation of MN and genetic polymorphisms was determined by molecular tests in lymphocytes from subjects involved in the study. Results It was determined that the frequency of MNs is 1.6 higher in the exposed group compared to the reference group (1.39 ± 0.92 versus 0.87 ± 0.78, p<0.0001). There was no increase in the frequency of MNs associated with the polymorphisms in GSTM1 and GSTT1. Conclusions The increase of MNs in car painters serves to alert the increased risk of cancer in this population exposed to organic solvents. These results can be used in Occupational Epidemiological Surveillance Programs, as a prevention strategy and policies to regulate and control the use of solvents at a national level and in other countries with a large informal sector of individuals exposed to these chemicals to reduce the risk of cancer.(AU)

Breast cancer surveillance for BRCA1/2 mutation carriers - is "early detection" early enough?

BACKGROUND: Annual MRI screening is associated with a significant reduction in advanced-stage breast cancer diagnosis in BRCA1/2 mutation carriers. The impact that early detection has on subsequent oncological treatment is less frequently reported. In this study we compared disease stage and therapeutic approaches in BRCA1/2 mutation carriers who developed breast cancer while adhering to the recommended surveillance scheme ("known carriers"), with women who became aware of their BRCA mutation status after breast cancer diagnosis ("latent carriers"). METHODS: Data on tumor characteristics, disease stage, and therapeutic decisions were collected on BRCA1/2 mutation carriers treated for breast cancer at the Chaim Sheba Medical Center. RESULTS: Data were available for 298 BRCA1/2 carriers. Median follow-up was 77.4 months (range, 3.5-520). Age at diagnosis was not statistically different between known carriers (n = 96; median age at diagnosis 44.7 years) and latent carriers (n = 202; 43.7 years); p = 0.8284. Of known carriers, 19.8% were diagnosed with carcinoma in situ vs. 5% of latent carriers (p = 0.0012). Stage T1N0 disease was diagnosed in 54/96 (56.3%) of known carriers vs. 59/202 (29.2%) of latent carriers (p < 0.00001). Neoadjuvant or adjuvant chemotherapy was administered to 46/96 (47.9%) of known carriers compared with 162/202 (80.2%) of latent carriers (p < 0.00001). CONCLUSIONS: While early stage breast cancer was diagnosed frequently among known BRCA1/2 carriers under tight surveillance, almost half of these women were treated with chemotherapy. Healthy BRCA1/2 mutation carriers should be informed about these rates while discussing risk-reducing surgical options.

Prophylactic breast irradiation reduces background parenchymal enhancement (BPE) on MRI: A secondary analysis.

PURPOSE: We recently showed that prophylactic breast irradiation (PBI) reduces the risk of contralateral breast cancer in BRCA mutation carriers undergoing treatment for early breast cancer. It has been suggested that Background Parenchymal Enhancement (BPE) may be a biomarker for increased risk of breast cancer. METHODS: For participants in the trial we reviewed the MRI prior to enrollment and following radiation treatment and scored the contralateral breast for BPE and density. RESULTS: Significant reduction of BPE was more commonly noted following PBI (p = 0.011) compared to the control group. CONCLUSION: Reduction of BPE by PBI may contribute to its prophylactic effect.

Genetic Protection Modifications: Moving Beyond the Binary Distinction Between Therapy and Enhancement for Human Genome Editing.

The current debate and policy surrounding the use of genome editing in humans typically relies on a binary distinction between therapy and human enhancement. Here, we argue that this dichotomy fails to take into account perhaps the most significant potential uses of CRISPR-Cas9 genome editing in humans. We argue that genetic treatment of sporadic Alzheimer's disease, breast and ovarian cancer predisposing BRCA1/2 mutations, and the introduction of human immunodeficiency virus resistance in humans should be considered within a new category of genetic protection treatments. We suggest that if this category is not introduced, life-altering research might be unnecessarily limited by current or future policy. Otherwise ad hoc decisions might be made, which introduce a risk of unforeseen moral costs, and might overlook or fail to address some important opportunities.

Value-based genomic screening: exploring genomic screening for chronic diseases using triple value principles.

BACKGROUND: Genomic screening has unique challenges which makes it difficult to easily implement on a wide scale. If the costs, benefits and tradeoffs of investing in genomic screening are not evaluated properly, there is a risk of wasting finite healthcare resources and also causing avoidable harm. MAIN TEXT: If healthcare professionals - including policy makers, payers and providers - wish to incorporate genomic screening into healthcare while minimizing waste, maximizing benefits, and considering results that matter to patients, using the principles of triple value (allocative, technical, and personal value) could help them to evaluate tough decisions and tradeoffs. Allocative value focuses on the optimal distribution of limited healthcare resources to maximize the health benefits to the entire population while also accounting for all the costs of care delivery. Technical value ensures that for any given condition, the right intervention is chosen and delivered in the right way. Various methods (e.g. ACCE, HTA, and Wilson and Jungner screening criteria) exist that can help identify appropriate genomic applications. Personal value incorporates preference based informed decision making to ensure that patients are informed about the benefits and harms of the choices available to them and to ensure they make choices based on their values and preferences. CONCLUSIONS: Using triple value principles can help healthcare professionals make reasoned and tough judgements about benefits and tradeoffs when they are exploring the role genomic screening for chronic diseases could play in improving the health of their patients and populations.

Coordination of Genetic Care: More Important and Complicated Than it Seems.

Families with hereditary risk for developing malignancy benefit from organized, coordinated care by a genetics professional. This report presents a case illustrating the potential errors that can occur when genetic care is fragmented and not coordinated, including ordering too much or not enough genetic testing, failing to communicate with the family who is at potential genetic risk, failing to communicate what the results of testing mean, and failing to recommend appropriate care, which may lead to psychosocial distress and late-detected cancers. This case highlights the complexities of genetic care and why management by a genetics professional results in more fiscally responsible care, appropriate genetic testing, and comprehensive care for all family members at risk.

Environmental factors and awareness of colorectal cancer in people at familial risk. / Fatores ambientais e conscientização sobre o câncer colorretal em pessoas com risco familiar.

OBJECTIVE: to identify the association between environmental risk factors and awareness of colorectal cancer in people at familial risk. METHOD: cross-sectional correlational study, with a sample consisted of people who met at least one of the Revised Bethesda criteria, and 80 participants were included in this study. A sociodemographic data record, the AUDIT Test for alcohol use, the Fagerström Test for tobacco smoking, the Estimation and Frequency of Food Intake scale, and the Cancer Awareness Measure questionnaire to assess the colorectal cancer awareness were used. Body mass index was calculated, and descriptive statistics and the Pearson's Correlation Coefficient were used to estimate the association. RESULTS: female sex predominated, with an average age of 37.8 years, almost half of the participants were overweight, 45% showed symptoms of alcohol dependence, half of the sample showed an association between hereditary factors and the development of colorectal cancer, and less than half of them were aware of cancer prevention programs. CONCLUSION: there is little information on the main environmental risk factors, signs and symptoms of colorectal cancer, and no significant association was found between these and colorectal cancer awareness.