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Research shows genetic counselors generally have pro-White implicit biases-both prejudice and stereotyping. Cultural competency training aims to foster equitable beliefs, behaviors, and attitudes in cross-cultural genetic counseling sessions, including those that are racially discordant (genetic counselors and patients are from different racial backgrounds). Therefore, cultural competency training has the potential to mitigate bias and reduce disparities. Here, we report the prevalence of cultural competency training among genetic counselors and associations between recency of training and counselors' racial biases. We conducted an online survey of genetic counselors and trainees in fall 2021. The survey assessed four types of bias (implicit/explicit prejudice and implicit/explicit stereotyping), time since last cultural competency training, time since last communication skills training, and frequency of clinic sessions with Black patients. Multiple linear regressions modeled associations between cultural competency training and different types of bias, adjusting for communication skills training, frequency of encounters with Black patients, and counselor race (White vs. non-White). Two hundred fifteen participants (107 genetic counselors and 108 trainees) responded, and 205 reported whether they had prior cultural competency training. Of these, 187 (91%) reported ever having cultural competency training, most (53%) of participants who had training had it within 6 months prior to survey completion. We found no clear pattern of associations between cultural competency training and racial biases (implicit or explicit) in adjusted analyses. Participants who had cultural competency training four or more years prior demonstrated less negative implicit stereotyping toward Black individuals compared with those having more recent training; but no statistically significant effect was found for participants who reported never having cultural competency training, compared with those having training more recently than 4 years prior. Overall, our findings do not support that cultural competency training is negatively associated with, or mitigates, Black/White racial prejudices and stereotypes against Black patients. These findings suggest more effective interventions are needed to reduce racial biases.
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To help advance research critical to the achievement of the National Society of Genetic Counselors' (NSGC) strategic objectives, coordination and prioritization of society resources are needed. NSGC convened a task force to advance research necessary for the achievement of our strategic objectives by reviewing existing society-supported research efforts identifying gaps in current research, and coordinating society resources, the task force was formed in order to coordinate and prioritize society resources to advance research critical to the achievement of our strategic objectives. The task force developed a research agenda outlining high-priority research questions for the next 5 years. The questions are organized into four domains: (a) Genetic Counseling Clients; (b) Genetic Counseling Process and Outcomes; (c) Value of Genetic Counseling Services; and (d) Access to Genetic Counseling Services. This framework can be used to advocate for research and funding priorities within NSGC and with other key research entities to stimulate the growth and advancement of the genetic counseling profession.
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Comités Consultivos , Consejeros , Asesoramiento Genético , Sociedades Médicas/organización & administración , Humanos , Informe de InvestigaciónRESUMEN
Even at the end of life, testing cancer patients for inherited susceptibility may provide life-saving information to their relatives. Prior research suggests palliative care inpatients have suboptimal understanding of genetic importance, and testing may be underutilized in this clinical setting. These conclusions are based on limited research. This study aimed to estimate genetic testing prevalence among high-risk palliative care patients in a National Cancer Institute-designated comprehensive cancer center. We also aimed to understand these patients' understanding of, and attitudes toward, hereditary cancer testing and DNA banking. Palliative care in-patients with cancer completed structured interviews, and their medical records were reviewed. Among patients at high risk for hereditary cancer, we assessed history of genetic testing/DNA banking; and related knowledge and attitudes. Among 24 high-risk patients, 14 (58.3%) said they/their relatives had genetic testing or they had been referred for a genetics consultation. Of the remaining 10 patients, seven (70%) said they would "probably" or "definitely" get tested. Patients who had not had testing were least concerned about the impact of future testing on their family relationships; two (20%) said they were "extremely concerned" about privacy related to genetic testing. Of patients without prior testing, five (50%) said they had heard or read "a fair amount" about genetic testing. No high-risk patients had banked DNA. Overall, 23 (95.8%) said they had heard or read "almost nothing" or "relatively little" about DNA banking. Written materials and clinician discussion were most preferred ways to learn about genetic testing and DNA banking. Overall, this study demonstrates underutilization of genetics services at the end of life continues to be problematic, despite high patient interest.
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Predisposición Genética a la Enfermedad , Conocimientos, Actitudes y Práctica en Salud , Neoplasias/genética , Cuidados Paliativos , Adulto , Proteína BRCA1/genética , Proteína BRCA2/genética , Femenino , Pruebas Genéticas/métodos , Humanos , Persona de Mediana EdadRESUMEN
Hereditary cancer genetic counseling often focuses on medically intensive risk-reduction strategies, like imaging and risk-reducing surgeries. Lifestyle factors also influence cancer risk, but health behavior counseling is not common in genetic counseling. Information about typical lifestyle risk factors among patients seeking hereditary cancer risk is sparse. The current study describes cancer risk-relevant lifestyle factors for people who have had cancer genetic testing. Data came from the Health Information National Trends Survey (HINTS 4) collected in 2013. Analytic variables represented American Cancer Society nutrition and physical activity guidelines. Lifestyle factors were assessed for people who had undergone testing for BRCA1, BRCA2, or Lynch Syndrome genes. Among 3016 HINTS respondents, 135 had cancer genetic testing. Of these, 58 % were overweight or obese. Eighteen percent reported no moderate-intensity physical activity. Average sedentary screen-time was 3.4 h (SE = 0.472) daily. Sixty-three percent drank non-diet soda, and 23 % of these people drank soda every day. Between 18 and 36 % consumed less than 2 ½ cups fruits/vegetables daily. Twenty-four percent were current smokers. Lifestyle risk factors were not different between people who had genetic testing and those who had not. In conclusion, most people who had genetic testing for cancer susceptibility have at least one modifiable risk factor. Genetic counselors have opportunities to impact a counselee's cancer risk not only through risk-tailored medical procedures, but also through lifestyle modification recommendations. Results of the current study may foster a broader discussion of genetic counselors' roles in healthy lifestyle education.
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Ejercicio Físico , Pruebas Genéticas , Conductas Relacionadas con la Salud , Estilo de Vida , Síndromes Neoplásicos Hereditarios/psicología , Adulto , Reparación de la Incompatibilidad de ADN , Femenino , Genes BRCA1 , Genes BRCA2 , Asesoramiento Genético , Humanos , Masculino , Persona de Mediana Edad , Mutación , Síndromes Neoplásicos Hereditarios/diagnóstico , Síndromes Neoplásicos Hereditarios/genética , Conducta de Reducción del Riesgo , Encuestas y CuestionariosRESUMEN
Family health history about cancer is an important prevention and health promotion tool. Yet few studies have identified family context factors that promote such discussions. We explored relations among family context (cohesion, flexibility, and openness), self-efficacy, and cancer communication (gathering family history, sharing cancer risk information, and frequency) in a diverse group of women enrolled in a randomized control trial. Baseline survey data for 472 women were analyzed. The women's average age was 34 years, 59% identified as Black, 31% had graduated high school, and 75% reported a family history of any cancer. Results showed that greater family cohesion and flexibility were related to higher communication frequency and sharing cancer information. Women who reported greater self-efficacy were more likely to have gathered family history, shared cancer risk information, and communicated more frequently with relatives. Openness was not associated with communication but was related to greater family cohesion and flexibility. Adjusting for demographic variables, self-efficacy, and family cohesion significantly predicted communication frequency. Women with higher self-efficacy were also more likely to have gathered family health history about cancer and shared cancer risk information. Future research may benefit from considering family organization and self-efficacy when developing psychosocial theories that in turn inform cancer prevention interventions.
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Comunicación , Salud de la Familia , Familia/psicología , Neoplasias/genética , Adulto , Relaciones Familiares , Femenino , Predisposición Genética a la Enfermedad , Humanos , Análisis Multivariante , AutoeficaciaRESUMEN
Women hold diverse beliefs about cancer etiology, potentially affecting their use of cancer preventive behaviors. Research has primarily focused on cancer causal attributions survivors and participants from non-diverse backgrounds hold. Less is known about attributions held by women with and without a family history of cancer from a diverse community sample. Participants reported factors they believed cause cancer. Open-ended responses were coded and relations between the top causal attributions and key factors were explored. Findings suggest certain socio-cultural factors play a role in the causal attributions women make about cancer, which can, in turn, inform cancer awareness and prevention messages.
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Conocimientos, Actitudes y Práctica en Salud , Neoplasias/psicología , Mujeres/psicología , Adulto , Características Culturales , Femenino , Humanos , Neoplasias/genética , Factores Sociológicos , Estados UnidosRESUMEN
This study explored relationships between worry, perceived risk for breast cancer, consulting a genetic counselor, having genetic testing, and genetic risk for women whose mothers had breast cancer. Analyses involved data from a community-based phone survey of women whose mothers had breast cancer. Participants were categorized as having low, intermediate, or high genetic risk based on their reported family history, in accordance with an accepted classification scheme. The Lerman Breast Cancer Worry Scale measured worry, and participants reported their perceived lifetime likelihood of breast cancer, risk compared to others, and chance from 1 to 100. ANOVA, chi-square, and multiple regression analyses were conducted as appropriate. One hundred-fifty women participated. Mean age was 38 years, and 81% were Caucasian. Fifty-two women had low, 74 had intermediate, and 24 had high genetic risk for breast cancer. There were no significant differences in worry or perceived risk by hereditary risk category. Most high-risk women (91%) had not spoken with a genetic counselor, and no one had previous genetic testing. These findings suggest perceived risk, worry about breast cancer, and use of expert consultation do not match the genetic contribution to risk. There is a need for effectively stratifying and communicating risk in the community and providing tailored reassurance or referral for high-risk assessment.
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Ansiedad , Neoplasias de la Mama/genética , Neoplasias de la Mama/psicología , Predisposición Genética a la Enfermedad , Adulto , Femenino , Asesoramiento Genético , Pruebas Genéticas , HumanosRESUMEN
OBJECTIVES: Universal screening of upper tract urothelial carcinoma (UTUC) for Lynch syndrome by mismatch repair (MMR) protein immunohistochemistry (IHC) has been recommended by some investigators. Herein, we assess this recommendation retrospectively by simulating its performance on a retrospective, unselected cohort of UTUCs, with comparison to the established setting of colorectal and endometrial adenocarcinoma. METHODS: We assessed for complete loss of MMR protein (MLH1, MSH2, MSH6, and PMS2) IHC in 74 consecutive cases of UTUC and then tabulated clinical and pathologic factors. MMR findings from same-institution colorectal and endometrial adenocarcinomas were tabulated for comparison. RESULTS: We observed loss of at least one MMR protein in 12% in our UTUC cohort (three MSH2/MSH6, three MSH6 only, one MLH1/PMS2, and two PMS2 only). Of these nine cases (seven males, two females, median age 67 years, five associated with colorectal adenocarcinoma), at least three (4% of the overall cohort) proved to be Lynch syndrome. Overall, MMR loss in UTUC was comparable to colorectal (11%; 50 of 471 cases) and endometrial (12%; 12 of 101 cases) adenocarcinomas. CONCLUSIONS: The rate of MMR loss observed in UTUC was comparable to that in the established setting of colorectal and endometrial adenocarcinomas, supporting universal UTUC screening at our institution and others.
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Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Reparación de la Incompatibilidad de ADN , Neoplasias Urológicas/química , Adenocarcinoma/química , Anciano , Neoplasias Colorrectales/química , Proteínas de Unión al ADN/análisis , Neoplasias Endometriales/química , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/análisis , Homólogo 1 de la Proteína MutL/análisis , Proteína 2 Homóloga a MutS/análisis , Estudios Retrospectivos , Neoplasias Urológicas/patología , Urotelio/patologíaRESUMEN
OBJECTIVE: This exploratory study assessed relationships among education, tolerance for ambiguity, and genetic testing awareness in light of implications for cancer genetics education. METHODS: Cross-sectional analyses were conducted from self-administered written survey data of a breast cancer risk communication trial, including 899 Women's Health patients recruited from 2003 to 2005. The modifying effect of tolerance for ambiguity on the relationship between educational background and breast cancer genetic testing awareness was assessed through logistic regression. RESULTS: There was a statistically significant main effect of education (p < 0.05), but not tolerance for ambiguity, on genetic testing awareness. However, the relationship between education and awareness was stronger among those with high tolerance for ambiguity (p for interaction <0.05), even when controlling for age, race, and breast cancer family history. Among persons with high (>1 SD above the mean) and medium tolerance for ambiguity, the relationship between education and awareness was positive and significant (p = 0.048 and 0.002, respectively). Among participants with low tolerance for ambiguity, the association was not significant. CONCLUSIONS: Educational background may predict awareness knowledge of breast cancer genetic testing only for those with higher tolerance for ambiguity. These findings could inform future intervention research concerning education about cancer genetic testing.
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Concienciación , Neoplasias de la Mama/genética , Pruebas Genéticas , Educación en Salud , Incertidumbre , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Recolección de Datos , Escolaridad , Salud de la Familia , Femenino , Humanos , Modelos Logísticos , Persona de Mediana Edad , Factores SocioeconómicosRESUMEN
PURPOSE: To summarize the impact of a family history of breast cancer on mammography practices and beliefs. METHOD: Survey data concerning breast health practices and beliefs were utilized for a cross-sectional analysis. Participants were 899 racially diverse nonpregnant women 40 years and older without breast cancer. The impact of various aspects of cancer family history on mammography, perceived barriers to and benefits of screening, and perceived breast cancer risk was assessed. RESULTS: More women with a first-degree relative with breast cancer reported a mammogram within the past year and rated their breast cancer risk higher. Death of a first-degree relative impacted the belief that breast cancer can be cured with early detection. Degree of relatedness of affected relative impacted mammography practice and risk perceptions. CONCLUSION: Family history of breast cancer impacted mammography adherence, beliefs about outcomes with early detection, and risk perceptions. Breast cancer death in a family may be a better predictor of beliefs about breast cancer detection and cure than family history of cancer alone. These findings have implications for how screening recommendations and risk information are communicated to patients with different familial cancer experiences.
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Actitud Frente a la Salud , Neoplasias de la Mama/prevención & control , Neoplasias de la Mama/psicología , Mamografía/psicología , Aceptación de la Atención de Salud , Adulto , Anciano , Neoplasias de la Mama/genética , Estudios Transversales , Femenino , Predisposición Genética a la Enfermedad , Humanos , Mamografía/estadística & datos numéricos , Persona de Mediana EdadRESUMEN
BACKGROUND: Gender differences in reported family cancer history could reduce the effectiveness of genetic screening for cancer risk. METHODS: We randomized 6 schools to teach ninth graders about health genealogy through workshops or offered a delayed intervention. We assessed the effect of the intervention on reported family history of various cancers along with gender and side of the family from which cancer was reported. RESULTS: Girls reported more breast cancer in the family. Both sexes reported more maternal relatives with breast cancer. There were no treatment group effects. CONCLUSIONS: There are gender differences in reported family history of breast cancer.
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Salud de la Familia , Educación en Salud/organización & administración , Anamnesis , Instituciones Académicas , Neoplasias de la Mama/genética , Neoplasias de la Mama/prevención & control , Neoplasias del Colon/genética , Neoplasias del Colon/prevención & control , Femenino , Humanos , Masculino , Educación del Paciente como Asunto , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/prevención & control , Servicios de Salud Escolar/organización & administración , Factores Sexuales , Encuestas y CuestionariosRESUMEN
Low participation among underserved populations in health research constrains progress in public health practices. From 2003 to 2005, Women's Health Clinic patients at the VCU Health System were recruited to a trial investigating breast cancer risk communication. In secondary analyses, we examined dimensions of the recruitment of these diverse women. The sample characteristics (age, insurance, race and previous mammograms) were compared to the overall clinic. Of recruitment attempts for eligible women, 45% consented; of those who declined, the top cited reasons were lack of time (40%) and lack of interest (18%). Of 899 participants, 35% qualified for the indigent care program, compared to 31% of the overall clinic (P<0.001). Forty-five percent of participants were African American, compared to 54% of overall clinic patients (P<0.001). Participants were younger (50 vs. 53 years, P<0.001) than the overall clinic population. Nonrepresentative enrollment of patients in clinical trials is common and could lead to suboptimal applicability of findings. Although there were statistically significant race and age differences between the study sample and the overall population, we demonstrate that waiting room recruitment can engage diverse women in a clinical trial and cancer risk communication.
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Neoplasias de la Mama/terapia , Comunicación , Aceptación de la Atención de Salud , Selección de Paciente , Ensayos Clínicos Controlados Aleatorios como Asunto , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , RiesgoRESUMEN
BACKGROUND: Reported family medical history may be the most widely accessible genomics screen currently available. The worth of any population-screening tool may be measured by parameters such as sensitivity and specificity. There is some evidence and theory suggesting that family history of breast cancer may be more frequently communicated about maternal (versus paternal) lines. If true, a discrepancy in reporting family history of breast cancer could mean suboptimal accuracy for this genomics-screening tool. METHODS: A cross-sectional analysis of reported family history of breast cancer was conducted beginning in early fall 2005 of data collected from April 2003 to March 2005. Study participants were Women's Health Clinic patients without breast cancer aged at least 40 years. The number of women reporting extended paternal relatives (e.g., aunts, grandmothers) with breast cancer was compared to the number of women reporting maternal relatives. RESULTS: More women reported a maternal relative with breast cancer (16%) compared to those reporting paternal relatives (10%) (McNemar odds ratio = 1.71, 95% confidence interval = 1.26 to 2.34). A discrepancy remained in analyses adjusting for potential covariates (race/ethnicity, awareness of breast cancer, family communication about breast cancer, and perceived risk). CONCLUSIONS: Self-reported family history of breast cancer may not optimally capture inherited risk from the father's side of the family. Further research is needed to look for modifiable contributors to this discrepancy to optimize screening for familial breast cancer.
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Neoplasias de la Mama/genética , Familia , Factores Sexuales , Adulto , Femenino , Humanos , Anamnesis , Encuestas y CuestionariosRESUMEN
Genetic breast cancer susceptibility testing presents ethical challenges for healthcare providers and their patients. The familial aspects of genetic information, recognition of DNA as a shared history and present common thread for all people and widespread misunderstandings of genetic tests all contribute to these challenges. In this article an ethical framework internationally developed as a charter for medical professionalism is used to guide approaches to ethical dilemmas of breast cancer genetic testing. Specifically, three ethical principles are explored as they relate to testing: primacy of patient, patient autonomy, and social justice. Approaching breast cancer genetic testing from this framework could help to ensure thoughtful and ethical practices in this rapidly evolving field.
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Neoplasias de la Mama/genética , Genes BRCA1 , Genes BRCA2 , Pruebas Genéticas/ética , Competencia Clínica , Femenino , Humanos , Justicia SocialRESUMEN
OBJECTIVES: To determine if intervention school students who received skills-based breast self-exam (BSE)/testicular self-exam (TSE) training were more likely than control school students to report higher intentions to perform BSE/TSE, greater BSE/TSE self-efficacy, and actual performance of BSE/TSE. METHODS: BSE/TSE behaviors, intentions, and self-efficacy were assessed in a high school-based trial (N = 6 schools; 3 schools randomized/condition) using self-reported data at 3 time points (N = 1058, 9 th grade students). RESULTS: At follow-up, intervention students had greater BSE/TSE intentions and self-efficacy than control students. Intervention students were more likely than control students to report monthly BSE (54.8% vs 27.2%, p = .031) and TSE (81.5% vs 31.4%, p = .010). CONCLUSIONS: Skills-based interventions with goal setting affect teenagers' self-examination behaviors, intentions, and self-efficacy. Teaching self-screening may empower teenagers to become more engaged in their preventive health, which may lead to improved health as they age.
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Neoplasias de la Mama/prevención & control , Educación en Salud/métodos , Conocimientos, Actitudes y Práctica en Salud , Autoexamen/métodos , Estudiantes , Neoplasias Testiculares/prevención & control , Adolescente , Femenino , Humanos , Masculino , Instituciones AcadémicasRESUMEN
Identifying women appropriate for cancer genetic counseling referral depends on patient-reported family history. Understanding predictors of reporting a high-risk family is critical in ensuring compliance with current referral guidelines. Our objectives were to (1) assess prevalence of candidates for BRCA1 and BRCA2 counseling referral in a primary care setting, (2) explore associations with high-risk status and various patient (e.g., race) and family structure (e.g., number of relatives) characteristics, and (3) determine whether high-risk patients had genetic counseling and/or testing. Survey and pedigree data were collected between 2010 and 2012 for 486 Women's Health Clinic patients. Analyses in 2013 investigated perceived cancer risk and worry, family structure, and receipt of genetic counseling. We explored whether these were associated with meeting USPSTF guidelines for genetic counseling referral. Twenty-two (4.5 %) women met the criteria for BRCA referral. Only one of these women had previous genetic counseling, and one reported prior genetic testing. Older women were more likely to meet BRCA referral criteria (P < 0.001). Although perceived risk was higher among high-risk women, 27 % of high-risk women felt their breast cancer risk was "low", and 32 % felt their risk was lower than average. About one in 22 women in primary care may require genetics services for hereditary breast and ovarian cancer, but alarmingly, few actually receive these services. Also, a significant proportion do not perceive that they are at increased risk. Educational interventions may be needed for both providers and patients to increase awareness of familial risk and appropriate genetic counseling services.
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BACKGROUND: Knowing family history is important for understanding cancer risk, yet communication within families is suboptimal. Providing strategies to enhance communication may be useful. METHODS: Four hundred ninety women were recruited from urban, safety-net, hospital-based primary care women's health clinics. Participants were randomized to receive the KinFact intervention or the control handout on lowering risks for breast/colon cancer and screening recommendations. Cancer family history was reviewed with all participants. The 20-minute KinFact intervention, based in communication and behavior theory, included reviewing individualized breast/colon cancer risks and an interactive presentation about cancer and communication. Study outcomes included whether participants reported collecting family history, shared cancer risk information with relatives, and the frequency of communication with relatives. Data were collected at baseline, 1, 6, and 14 months. RESULTS: Overall, intervention participants were significantly more likely to gather family cancer information at follow-up (odds ratio [OR]: 2.73; 95% confidence interval [CI]: 2.01, 3.71) and to share familial cancer information with relatives (OR: 1.85; 95% CI: 1.37, 2.48). Communication frequency (1=not at all; 4=a lot) was significantly increased at follow-up (1.67 vs. 1.54). Differences were not modified by age, race, education, or family history. However, effects were modified by pregnancy status and genetic literacy. Intervention effects for information gathering and frequency were observed for nonpregnant women but not for pregnant women. Additionally, intervention effects were observed for information gathering in women with high genetic literacy, but not in women with low genetic literacy. CONCLUSIONS: The KinFact intervention successfully promoted family communication about cancer risk. Educating women to enhance their communication skills surrounding family history may allow them to partner more effectively with their families and ultimately their providers in discussing risks and prevention.
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Neoplasias de la Mama/genética , Comunicación , Familia , Predisposición Genética a la Enfermedad , Conocimientos, Actitudes y Práctica en Salud , Adolescente , Adulto , Femenino , Humanos , Tamizaje Masivo , Persona de Mediana Edad , Virginia , Adulto JovenRESUMEN
PURPOSE: The availability of genetic tests for cancer susceptibility is increasing. Current tests, however, have limited clinical sensitivity. Even when clinically valid tests are available, the genetic counseling and informed consent process might not be feasible for dying patients with cancer. DNA banking preserves the opportunity for future research or clinical testing and may provide critical opportunities for surviving relatives. This study explored the current practices and potential for DNA banking for cancer susceptibility among oncologists specializing in palliative care. METHODS: Palliative care oncologists actively providing clinical care for dying patients with cancer were recruited for an online survey. Descriptive statistics for DNA banking practices, perceived qualification to recommend banking, and potential predictors were assessed. RESULTS: Data were collected from 49 physicians (37% recruitment rate). Eighty percent reported assessing at least some patients for genetic cancer susceptibility in the past 12 months. No participants reported banking DNA for patients in the past 12 months. Only 5% reported feeling at least somewhat qualified to order DNA banking. A Web-based risk assessment tool and genetic counselor on staff were perceived as the most helpful potential resources. CONCLUSION: Despite its potential, DNA banking is not being used by palliative care oncologists.
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We introduced a K1702M mutation in the BRCA1 BRCT domain known to prevent the binding of proteins harboring pS-X-X-F motifs such as Abraxas-RAP80, BRIP1, and CtIP. Surprisingly, rather than impairing homologous recombination repair (HRR), expression of K1702M resulted in hyper-recombination coinciding with an accumulation of cells in S-G2 and no effect on nonhomologous end-joining. These cells also showed increased RAD51 and RPA nuclear staining. More pronounced effects were seen with a naturally occurring BRCT mutant (M1775R) that also produced elevated levels of ssDNA, in part co-localizing with RPA, in line with excessive DNA resection. M1775R induced unusual, thread-like promyelocytic leukemia (PML) nuclear bodies and clustered RPA foci rather than the typical juxtaposed RPA-PML foci seen with wild-type BRCA1. Interestingly, K1702M hyper-recombination diminished with a second mutation in the BRCA1 RING domain (I26A) known to reduce BRCA1 ubiquitin-ligase activity. Thesein vitro findings correlated with elevated nuclear RAD51 and RPA staining of breast cancer tissue from a patient with the M1775R mutation. Altogether, the disruption of BRCA1 (BRCT)-pS-X-X-F protein binding results in ubiquitination-dependent hyper-recombination via excessive DNA resection and the appearance of atypical PML-NBs. Thus, certain BRCA1 mutations that cause hyper-recombination instead of reduced DSB repair might lead to breast cancer.
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Proteína BRCA1/genética , Mutación , Recombinación Genética , Secuencias de Aminoácidos , Proteína BRCA1/química , Proteína BRCA1/metabolismo , Sitios de Unión , Neoplasias de la Mama/genética , Proteínas Portadoras/metabolismo , Línea Celular Tumoral , Núcleo Celular/metabolismo , Núcleo Celular/ultraestructura , ADN/genética , ADN/metabolismo , Reparación del ADN , Endodesoxirribonucleasas , Femenino , Vectores Genéticos , Células HEK293 , Humanos , Proteínas Nucleares/metabolismo , Proteína de la Leucemia Promielocítica , Unión Proteica , Estructura Terciaria de Proteína , Recombinasa Rad51/metabolismo , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/metabolismo , UbiquitinaciónRESUMEN
Cancer patient communication is always embedded in a complex background of inter-related parts, that is, a system. Cancer patients specifically are exposed to a health care system. Considering this context, this article summarizes the insights from a roundtable discussion involving behavioral medicine and oncology experts convened at the 2008 Annual Meeting of the Society of Behavioral Medicine as part of an annual preconference course entitled "Interpersonal Communication and Cancer Control: Emerging Themes." In this article we summarize the communication-relevant components of health care systems, focusing on the macro level. Next, we review existing theoretical frameworks for systems-based communication, the unique aspects of "systems thinking," and the emerging systems tools that can be integrated in cancer communication. Finally, we propose a research agenda for successful system approaches for patient-centered cancer communication.