Reported Family History Research Articles

Factorial structure and familial aggregation of the Hypomania Checklist-32 (HCL-32): Results of the NIMH Family Study of Affective Spectrum Disorders

BackgroundThere is substantial evidence that bipolar disorder (BD) manifests on a spectrum rather than as a categorical condition. Detection of people with subthreshold manifestations of BD is therefore important. The Hypomania Checklist-32 (HCL-32) was developed as a tool to identify such people. PurposeThe aims of this paper were to: (1) investigate the factor structure of HCL-32; (2) determine whether the HCL-32 can discriminate between mood disorder subtypes; and (3) assess the familial aggregation and cross-aggregation of hypomanic symptoms assessed on the HCL with BD. ProceduresNinety-six probands recruited from the community and 154 of their adult first-degree relatives completed the HCL-32. Diagnosis was based on semi-structured interviews and family history reports. Explanatory factor analysis and mixed effects linear regression models were used. FindingsA four-factor (“Activity/Increased energy,” “Distractibility/Irritability”, “Novelty seeking/Disinhibition, "Substance use") solution fit the HCL-32, explaining 11.1% of the total variance. The Distractibility/Irritability score was elevated among those with BP-I and BP-II, compared to those with depression and no mood disorders. Higher HCL-32 scores were associated with increased risk of BD-I (OR = 1.22, 95%CI 1.14–1.30). The “Distractibility/Irritability” score was transmitted within families (β = 0.15, p = 0.040). However, there was no familial cross-aggregation between mood disorders and the 4 HCL factors. ConclusionsOur findings suggest that the HCL-32 discriminates the mood disorder subtypes, is familial and may provide a dimensional index of propensity to BD. Future studies should explore the heritability of symptoms, rather than focusing on diagnoses.

Reliability of Family History Report among Relatives of Aggressive Periodontitis Patients

To assess the periodontal status among relatives of aggressive periodontitis (AgP) patients and to evaluate the reliability of the family history report as provided by the proband.Fifty AgP patients were identified during 2005/2006 as fulfilling the criteria to be diagnosed as AgP as outlined in the 1999 international classification system for periodontal disease. These subjects met the clinical criteria for either localized or generalized AgP.It was considered that AgP patients should be informed of the genetic nature of their condition and that other blood relatives could be at risk. The results would suggest that the screening of relatives with a positive family history could be justified as a standard procedure, but negative family history reports are unlikely to yield significant numbers of affected relatives and may not be a justifiable use of scarce resources.The report given by the proband was considered reliable. If the report was positive, it was followed by diagnosis of periodontitis in 73% of the cases, while if it was negative, periodontitis was absent in 66% of the cases.

Psychosocial Risk Factors and Other Than Honorable Military Discharge: Providing Healthcare to Previously Ineligible Veterans.

In response to a strong focus on suicide prevention for all veterans, the Department of Veterans Affairs (VA) recently revised policy to provide emergency mental healthcare for veterans who received Other Than Honorable (OTH) discharges from the military. This current study takes a preliminary step toward identifying demographic, historic, military, clinical, and social characteristics of veterans with OTH discharges. N = 1,172 Iraq/Afghanistan-era veterans were evaluated between 2005 and 2016 in the multi-site VA Mid-Atlantic Mental Illness, Research, Education and Clinical Center (MIRECC) Study of Post-Deployment Mental Health (PDMH Study). Veterans with OTH discharges constituted 2.7% of our sample, approximating the estimated rate in the overall U.S. veteran population. Compared to veterans discharged under honorable conditions, veterans with OTH discharges were more likely to be younger and have greater odds of reporting family history of drug abuse and depression. Further, veterans with OTH discharges reported a lower level of social support and were more likely to be single, endorse more sleep problems, score higher on measures of drug misuse, have a history of incarceration, and meet diagnostic criteria for major depressive disorder. A subsequent matching analysis provided further evidence of the association between OTH discharge and two risk factors: drug misuse and incarceration. These findings elucidate potential factors associated with veterans with OTH discharges, particularly substance abuse and criminal justice involvement. Results also indicate higher incidence of risk factors that often accompany suicidal ideation and should be a highlighted component of healthcare delivery to this vulnerable cohort of veterans.

Germline pathogenic variants in patients with pheochromocytoma.

668 Background: Approximately 25% of pheochromocytomas (PCC) have a hereditary basis, and germline variants in the SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX, VHL, FH, RET, MEN1, and NF1 genes have been associated with a predisposition to PCC and paraganglioma (PGL). Multi-gene hereditary cancer panel testing for PCC has become increasingly more common than single-gene testing algorithms. Identification of a pathogenic or likely pathogenic variant (PV/LPV) in one of these genes has important implications for surveillance in patients and their family members. Here we describe the spectrum of PV/LPV variants identified in individuals with PCC. Methods: We performed a retrospective review of clinical and molecular data for all individuals diagnosed with PCC who underwent panel testing through BioReference Laboratories that included at least SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX, VHL, FH, RET, MEN1, and NF1 between January 2016 and February 2017. Results: Seventy-nine individuals underwent testing due to a personal (n = 76) or family (n = 3) history of PCC. The positive yield was 14% (11/79). The majority of PV/LPV were in SDHB (n = 4; 36%), followed by RET (n = 2, 18%), with the remaining variants being identified in SDHA (1), SDHC (1), VHL (1), TMEM127 (1), and MAX (1). Approximately half (6/11) of those with a PV/LPV had a non-syndromic presentation of a unilateral PCC with no reported family history of PCC or PGL. The average age at tumor diagnosis was lower for probands testing positive than those without PV/LPV (34y±14 vs 44y±16). Conclusions: Our data support previous recommendations that patients with apparently sporadic, non-syndromic PCC be considered for genetic testing. Panel testing is a useful tool for identifying individuals with hereditary PCC.

Bilateral Renal Hypoperfusion Following Motor Vehicle Accident.

Renal hypoperfusion noted on abdominal computed tomography (CT) scan without any underlying comorbid condition is a rare finding. Most reported cases of renal hypoperfusion have an association with an underlying cardioembolic problem, such as atrial fibrillation, endocarditis, cardiomyopathies, or artificial valve thrombi. We present a case of transient renal hypoperfusion evident on abdominal CT scan following blunt trauma. An 18-year-old male without any significant past medical history presented to the emergency department with the complaint of abdominal pain. The patient reported history of motor vehicle accident 1 week prior to his presentation. He was a front seat passenger wearing a seatbelt when the car went into a ditch. Airbags were deployed and the patient briefly lost consciousness. He presented 1 week later with complaints of generalized abdominal pain, more on the left side that started a few days after his accident, nonradiating, constant, 4/10 intensity. He denied dysuria, hematuria, groin pain, fever, chills, nausea, vomiting, abdominal pain, diarrhea, constipation, decreased oral intake, joint pain, leg swelling, or redness. He denied any medication use or any history of intravenous drug abuse. There was no reported family history of kidney disease or blood clots. Initial laboratory tests, including complete blood count, basic metabolic panel, erythrocyte sedimentation rate, and urinalysis were unremarkable except trace protein on the urinalysis. Contrast-enhanced CT of the abdomen showed multiple, confluent, focal areas of hypoperfusion of the renal parenchyma bilaterally. Given the CT findings of bilateral renal hypoperfusion, the patient was admitted to the hospital and an extensive workup was performed to rule out cardioembolic etiology. Echocardiogram, renal ultrasound, magnetic resonance angiogram of the abdomen, vasculitis panel, and hypercoagulable workup was unremarkable. The CT findings of renal hypoperfusion were considered secondary to transient hypoperfusion from blunt trauma. Abdominal pain resolved with nonsteroidal anti-inflammatory drugs and he was discharged to home. Follow-up abdominal CT scan with contrast obtained a few months later showed normal kidneys with resolution of previously noted renal hypoperfusion. Our case highlights a benign incidental finding of bilateral renal hypoperfusion following motor vehicle accident (with airbag injury), which resolved on follow-up imaging. On literature search, such CT scan findings of transient renal hypoperfusion of unclear significance have not been previously reported. Even though our patient underwent extensive workup to rule out cardioembolic etiology, it may be reasonable to forego such workup following blunt abdominal trauma.

All-Cause Mortality for Life Insurance Applicants with a Family History of Coronary Artery Disease Before 60.

-To determine the all-cause mortality of life insurance applicants having a family history of coronary artery disease (CAD) before age 60. -Epidemiological studies have shown that a family history of premature CAD is an independent risk factor for CAD events. The strength of the association between family history and CAD is greatest with earlier age of presentation of CAD in the family member and when multiple family members are affected. Despite earlier insurance studies on this relationship, there is sparse current data on the association between family history of CAD and all-cause mortality in life insurance applicants. -Life insurance applicants with reported family history of Coronary Artery Disease (CAD) were extracted from data covering United States residents between October 2009 and October 2016. Information about these applicants was matched to the Social Security Death Master (SSDMF) file for deaths occurring from 2009 to 2012 and to another commercially available death source file (Other Death Source, ODS) for deaths occurring from 2009 to 2016 to determine vital status. Actual to Expected (A/E) mortality ratios were calculated using the Society of Actuaries 2015 Valuation Basic Table (2015VBT), select and ultimate table (age last birthday). All expected bases were not smoker distinct. Confidence bands around these mortality ratios were calculated. The variables of interest were applicant age, gender, number of family members with CAD before age 60, and the presence of cardiac or cardiovascular conditions. -Overall, the mortality of applicants with family members with a history of CAD before age 60 was slightly lower than expected mortality based on the 2015 VBT. Applicants with a cardiac or cardiovascular comorbid condition had a significantly higher mortality ratio. For applicants aged 25-54 and 65-75 with cardiac comorbid conditions, the mortality ratio was 2 times that of those without a cardiac comorbid condition. For those aged 55-64 with cardiovascular comorbid conditions, the mortality ratio was 2.9 times that of those without a cardiovascular comorbid condition. Females had a slightly higher mortality ratio for all age groups, number of family members with CAD before age 60, and cardiovascular conditions. -A family history of CAD before the age of 60 in an insurance applicant may be associated with increased all-cause mortality. Overall in this study, life insurance applicants had a mortality slightly lower than the expected mortality based on the 2015 VBT. However, applicants with a positive family history and a cardiac or cardiovascular comorbid condition had a significantly higher mortality ratio.

Prevalence of Oral Premalignant Lesions and Its Risk Factors among the Adult Population in Udupi Taluk of Coastal Karnataka, India

Objective:Globally oral cancer is one of the ten most common cancers with prevalence being high in Central and South East Asian countries. This survey was conducted to estimate the prevalence of oral pre-malignant lesions (OPML) and to identify their risk factors.Methods:A community based cross-sectional study was carried out among 2033 individuals aged ≥18 years. A questionnaire was administered to collect socio-demographic characteristics, various risk factors for oral cancer and presence of its symptoms. Oral cavity of all the participants was examined in detail by the study investigator as per WHO guidelines for the early diagnosis of oral neoplasia.Result:The prevalence of OPML was found to be 3.73%. Among those with OPML, all were ever tobacco consumers and had poor oral hygiene. A significant association was observed between OPML and younger age group (OR=2.56, 95% CI 1.08-6.02), males (OR=26.76, 95% CI 8.40-85.19) and low socio-economic status (OR = 1.91, 95% CI 1.20-3.02). Tobacco (p<0.001), alcohol (OR= 7.92, 95% CI 4.77-13.14) and areca nut consumption (OR = 5.48, 95% CI 3.42-8.77) were strongly associated with OPML. On multivariate analysis among ever tobacco users, OPML was associated with younger individuals, males and those using smokeless forms of tobacco (p <0.05). The study showed that the participants with OPML were more likely to be never married (OR=1.6, 95% CI 0.92-2.96), to be unskilled workers (OR= 1.45, 95% CI 0.61-3.43), to have suffered from oral trauma (OR =1.30, 95% CI 0.75-2.26), to have consumed hot and spicy food frequently (OR=1.53, 95% CI 0.96-2.24), to have consumed fruits infrequently (OR=1.53, 95% CI 0.90-2.59) and to report family history of any cancer (OR = 1.29, 95% CI 0.58-2.87). However, these associations were statistically insignificant.Conclusion:The study reinforces that use of substances such as tobacco, alcohol and areca nut are the modifiable risk factors for OPML.

Clinicopathological characteristics of cutaneous malignant melanoma in patients at a tertiary hospital in Macaronesia. Survival as a function of locoregional prognostic factors per the American Joint Committee on Cancer.

Despite suffering high ultraviolet radiation levels, few data on malignant melanoma (MM) in Macaronesia are available. Observational study of cutaneous MM cases diagnosed during a period of 12 years at a tertiary hospital in Canary Islands. A total of 532 patients (female/male = 1.4) with an average age of 56 years were included; 5% developed more than one MM, and 7% reported family history of MM. Phototype II (43%), dark eyes (41%), and dark hair (41%) predominated. There was a lower frequency of light-colored hair and eyes in those born in the Canary Islands. The most frequent locations of MM were on the back for men (37%) and on the lower extremities for women (35%). Among the infiltrating tumors (83%), the (median) thickness was 1.07 mm (women, 0.90 mm; men, 1.21 mm). Anatomopathological ulceration (AU) and a mitotic rate ≥1 mitosis/mm2 (HMR) were recorded in 27% of patients. Patients with regional disease constituted 12% of the population. The most common stage was IA (34%). Melanoma-specific survival (MSSV) decreased significantly with thickness, presence of AU, HMR, and sentinel lymph node disease. These four variables were independent prognostic factors. The five-year MSSV varied between 100% (stage IA) and 39% (stage IIIC). The characteristics of the patients were similar to those published in datasets from continental Europe, although the pigmentary features were darker in those originating from Macaronesia. The prognostic parameters described in the 7th edition of the American Joint Committee on Cancer (AJCC) independently predict MSSV in our patients.

The Impact of Family History on the Clinical Features of Huntington’s Disease

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. In most cases the disease is inherited from a parent, although a considerable number of affected persons have no reported family history of the disease. While CAG repeat length is negatively correlated with age of symptom onset, variability exists suggesting that other variables may influence symptom onset. The objective of this study is to determine whether awareness of a family history of HD has an impact on symptom onset and disease manifestations. Data were obtained from Enroll-HD to compare subjects with a family history of HD to subjects without on various key clinical outcomes. In addition, multiple regressions were performed to investigate the impact of family history on the age at onset of depression and motor symptoms. 4,285 mutation positive subjects were included in the analysis, of which 4.81% had a negative family history. Controlling for CAG repeat length, a positive family history predicted an onset of depression 11.438 years earlier and an onset of motor symptoms 6.681 years earlier when compared to having a negative family history. Subjects with a positive family history were more likely to report behavioral manifestations as the initial major symptom of HD (38.6% vs. 29.6%, p = 0.023), and were more likely to report previous suicidal ideation/attempts (26.2% vs. 20.3%, p = 0.046). A positive family history of HD appears to be associated with an earlier onset of depression and overall disease manifestations. Implications regarding the role of genetic versus environmental contributions to symptom onset in HD are discussed.

Heart failure: Pilot transcriptomic analysis of cardiac tissue by RNA-sequencing.

Despite left ventricular (LV) dysfunction contributing to mortality in chronic heart failure (HF), the molecular mechanisms of LV failure continues to remain poorly understood and myocardial biomarkers have yet to be identified. The aim of this pilot study was to investigate specific transcriptome changes occurring in cardiac tissues of patients with HF compared to healthy condition patients to improve diagnosis and possible treatment of affected subjects. Unlike other studies, only dilated cardiomyopathy (DCM) (n = 2) and restrictive cardiomyopathy (RCM) (n = 2) patients who did not report family history of the disease were selected with the aim of obtaining a homogeneous population for the study. The transcriptome of all patients were studied by RNA-sequencing (RNA-Seq) and the read counts were adequately filtered and normalized using a recently developed user-friendly tool for RNA-Seq data analysis, based on a new graphical user interface (RNA-SeqGUI). By using this approach in a pairwise comparison with healthy donors, we were able to identify DCM- and RCM-specific expression signatures for protein-coding genes as well as for long noncoding RNAs (lncRNAs). Differential expression of 5 genes encoding different members of the mediator complex was disclosed in this analysis. Interestingly, a significant alteration was found for genes which had never been associated with HF until now, and 27 lncRNA/mRNA pairs that were significantly altered in HF patients. The present findings revealed specific expression pattern of both protein-coding and lncRNAs in HF patients, confirming that new LV myocardial biomarkers could be reliably identified using Next-Generation Sequencing-based approaches.

Sex differences in LRRK2 G2019S and idiopathic Parkinson's Disease.

ObjectiveTo evaluate sex differences and the relative effect of G2019S LRRK2 mutations in Parkinson's disease (PD).Methods530 LRRK2 PD carriers and 759 noncarrier PD (idiopathic, IPD) evaluated as part of the Fox Foundation (MJFF) Consortium were included. All participants completed a study visit including information on clinical features, treatment, examination, and motor and nonmotor questionnaires. Clinical features were compared between men and women separately for IPD and LRRK2 PD; and features were compared between IPD and LRRK2 PD separately for men and women.Results Among IPD: men had higher levodopa equivalency dose (LED), worse activities of daily living and motoric severity but lower complications of therapy (UPDRS‐IV). IPD women had higher olfaction and thermoregulatory scores and were more likely to report family history of PD. Among LRRK2 PD: Male predominance was not observed among G2019S LRRK2 cases. Women had worse UPDRS‐IV but better olfaction. Among same sex:LRRK2 men and women had better olfaction than IPD counterparts. LRRK2 men demonstrated lower motor and higher cognitive, RBD and thermoregulation scores than IPD men and LRRK2 women had greater UDPRS‐IV and rates of dyskinesia.InterpretationThere were clinical differences between sexes with a more severe phenotype in IPD men and more complications of therapy in women. The more severe male phenotype was moderated by LRRK2, with LRRK2 men and women showing less diversity of phenotype. Our study supports that both genetics and sex drive phenotype, and thus trials in LRRK2 and IPD should consider gender stratification in design or analysis.

Expect the Unexpected in a Colonoscopy: A Case of Colonic Endometriosis

Endometriosis is defined by the presence and the proliferation of endometrial tissue outside the uterus. Estimate prevalence is nearly 10-15% in women of reproductive age group. Symptoms vary according to location where endometrial tissue is implanted. Intestinal endometriosis can occur in up to 37% of all cases of endometriosis, mainly affecting recto sigmoid part of colon. Our patient is a 32-year-old female with past history of infantile cerebral palsy, seizure disorder and chronic constipation presented to our gastroenterology clinic with abdominal pain. Symptoms have been waxing and waning for years, described as diffuse abdominal pain, cramping in nature and associated with severe constipation. Patient denied any other symptoms, including hematemesis, hematochezia or melena. Patient reported family history of unknown cancer. Physical exam was remarkable for scars from previous cesarean sections. No abdominal tenderness, guarding or rigidity was appreciated. Basic laboratory testing was unremarkable. Colonoscopy visualized a 1 cm sessile polyp (figure 1) in descending colon that was snared, cauterized and retrieved (figure 2). Histology of the polyp revealed benign endometrial glands and stroma, consistent with diagnosis of endometriosis. Patient was started on oral contraceptive medication with dramatic improvement of abdominal pain before patient preferentially stopped it due to weight gain. A follow up colonoscopy for recurrent abdominal pain visualized diminutive polyp in the sigmoid colon that was removed by snare polypectomy. Pathology was consistent with hyperplastic polyp. On outpatient follow up, patient denied any more symptoms of abdominal pain. Endometriosis is a hormone responsive pathological implanting of endometrial tissue outside the uterus. Symptoms of endometriosis vary. Intestinal endometriosis usually manifests as alteration in bowel habits, rectal bleeding and dyschezia. Our patient presented with non-specific abdominal pain that initially responded with oral contraceptive medication. Although patient with diagnosis of endometriosis usually tend to be infertile unless treated, our patient had delivered more than once before she was diagnosed with endometriosis. We present this case so we as gastroenterologist and internists would have low index of suspecion of this rare pathology.Figure: Colonoscopy visualized a 1 cm sessile polyp in the descending colon.Figure: Appearance of bleeding polyp after it was snared and cautarized.

Abstract 4271: Population-wide vs. carrier-probability-based BRCA1/2 mutation testing in the Washington Ashkenazi Study

Abstract Background: Currently, women are referred for BRCA1/2 mutation testing if their family history of breast and ovarian cancer indicates they have sufficient probability of carrying mutations. In contrast, calls have intensified for population-wide testing for BRCA1/2 founder mutations among Ashkenazi Jews, due to relatively high mutation prevalence (2.5%) and decreasing genotyping costs. However, population-wide testing would strain genetic counseling resources and incur costs from testing mostly mutation-negative women. We compared the performance of population-wide vs. carrier-probability-based BRCA1/2 testing in the community-based Washington Ashkenazi Study (WAS). Methods: BRCA1/2 carrier-probabilities based on reported family histories were calculated using BRCAPRO for 4589 probands (102 BRCA1/2 mutation-carriers) in WAS. For each carrier-probability threshold, we compared the percent of mutations found (sensitivity) vs. the percent of women requiring mutation testing, overall and by proband age. At example carrier-probability thresholds, undetected and detected carriers’ attributes were compared using nonparametric tests. Results: A 1.2% carrier-probability threshold identified 80% of BRCA1/2 mutations in the 35% of women with highest carrier-probability. For women under age 40, 94% of BRCA1/2 mutations were identified in the 50% of women with highest carrier-probability. Compared to identified mutation-carriers, missed mutation-carriers had no personal cancer history, no affected first- and second-degree relatives (p&amp;lt;0.0001), more unaffected first-degree relatives (p=0.0002), and were older (p=0.012; median age=53). Conclusion: Carrier-probability-based BRCA1/2 mutation testing identified large majorities of mutation-carriers and would have avoided testing for many mutation-negative women. Missed mutation-carriers were older and cancer-free and would gain minimal benefit from risk-reducing interventions. A cost-effective carrier-probability threshold could acceptably tradeoff identifying BRCA1/2 mutation carriers before they get cancer while testing as few women as possible. Citation Format: Ana F. Best, Margaret A. Tucker, Hormuzd A. Katki. Population-wide vs. carrier-probability-based BRCA1/2 mutation testing in the Washington Ashkenazi Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4271. doi:10.1158/1538-7445.AM2017-4271

Hereditary factors are unlikely behind unusual pattern of early - Onset colorectal cancer in Egyptians: A study of family history and pathology features in Egyptians with large bowel cancer (cross-sectional study)

BackgroundColorectal cancer in Egypt has a higher incidence in young patients compared to western countries, where the disease is more prevalent in the old age group. This difference has been attributed to higher incidence of hereditary cancers in young Egyptian patients. The aim of this study is to compare the family history criteria and pathology features of tumors in young (≤40 years) and old (>40 years) Egyptian patients with adenocarcinoma of the colon and rectum. Materials and methodsThis is the analysis of our prospectively collected data on the pathology features of tumors in 313 consecutive patients (133 young, 180 old) with colorectal cancer presenting to the Department of Surgery within an eight-year period. A detailed family history was obtained from 258 patients (112 young, 146 old). Results41 young and 48 old patients reported family history of cancer, the difference was not statistically significant. Ten young patients (9%) reported a family history of colorectal cancer in a first degree relative (3 fitting into Amsterdam criteria, 7 fitting into less strict criteria) which was not significantly different from the old age group. The pathologic features of tumors in both groups resembled sporadic rather than hereditary cancer and there was no significant difference between groups in tumor location, degree of differentiation, mucin production, synchronous and metachronous colorectal tumors or polyps and grossly stricturing or ulcerating tumors. Extracolonic tumors developed in one young and two old patients. ConclusionThe characteristics of large bowel cancer in young Egyptian patients do not differ significantly from those in older patients. Despite the high incidence of large bowel cancer in young Egyptian patients, family history and pathologic features of tumors do not support a hereditary origin of colorectal cancer in this age group in Egypt.

Awareness, knowledge, perceptions, and attitudes towards genetic testing for cancer risk among ethnic minority groups: a systematic review

BackgroundGenetic testing for risk of hereditary cancer can help patients to make important decisions about prevention or early detection. US and UK studies show that people from ethnic minority groups are less likely to receive genetic testing. It is important to understand various groups’ awareness of genetic testing and its acceptability to avoid further disparities in health care. This review aims to identify and detail awareness, knowledge, perceptions, and attitudes towards genetic counselling/testing for cancer risk prediction in ethnic minority groups.MethodsA search was carried out in PsycInfo, CINAHL, Embase and MEDLINE. Search terms referred to ethnicity, genetic testing/counselling, cancer, awareness, knowledge, attitudes, and perceptions. Quantitative and qualitative studies, written in English, and published between 2000 and 2015, were included.ResultsForty-one studies were selected for review: 39 from the US, and two from Australia. Results revealed low awareness and knowledge of genetic counselling/testing for cancer susceptibility amongst ethnic minority groups including African Americans, Asian Americans, and Hispanics. Attitudes towards genetic testing were generally positive; perceived benefits included positive implications for personal health and being able to inform family. However, negative attitudes were also evident, particularly the anticipated emotional impact of test results, and concerns about confidentiality, stigma, and discrimination. Chinese Australian groups were less studied, but of interest was a finding from qualitative research indicating that different views of who close family members are could impact on reported family history of cancer, which could in turn impact a risk assessment.ConclusionInterventions are needed to increase awareness and knowledge of genetic testing for cancer risk and to reduce the perceived stigma and taboo surrounding the topic of cancer in ethnic minority groups. More detailed research is needed in countries other than the US and across a broader spectrum of ethnic minority groups to develop effective culturally sensitive approaches for cancer prevention.

Identifying women at high-risk for breast cancer using data from the electronic health record compared to self-report.

e13044 Background: One of the barriers to chemoprevention uptake among high-risk women is the lack of routine breast cancer risk assessment in the primary care setting. We calculated breast cancer risk using the Breast Cancer Surveillance Consortium (BCSC) model, which accounts for age, race/ethnicity, first-degree family history of breast cancer, benign breast disease, and mammographic density, using data collected from the electronic health record (EHR) compared to self-report. Methods: Among women undergoing screening mammography, we collected breast cancer risk information from the EHR and a self-administered survey. Eligibility criteria for calculating 5-year invasive breast cancer risk using the BCSC model included age 35-74, no prior history of breast cancer, mastectomy, or breast augmentation. We extracted data on demographics, structured first-degree family history, breast radiology and pathology reports from the EHR. We assessed agreement in breast cancer risk information between the EHR and self-report data. Results: Among 13,735 women with EHR data for BCSC risk calculation, 2708 women (20%) met high-risk criteria, based upon a 5-year breast cancer risk ≥1.67%. Among high-risk women, 2% were age 40-49, 23% age 50-59, 48% age 60-69, and 26% age 70-74. From the EHR, data was missing on 31% for race/ethnicity and 85% for family history. Among 2320 women with both EHR and self-report data, more complete information was available for race/ethnicity, family history, and breast biopsies in the surveys. More first-degree family history (14% vs. 3%) and prior breast biopsies (18% vs. 11%) were identified by self-report vs. EHR, respectively. However, more women with atypia and lobular carcinoma in situwere identified from the EHR. More high-risk women (20% vs. 16%) were identified with EHR vs. survey data, respectively, with correlation of 0.82. Conclusions: Among women undergoing screening mammography, we identified 20% who met high-risk criteria according to the BCSC model based upon EHR data, despite missing information on race/ethnicity, family history, and prior breast biopsies. This may serve as an initial screen for identifying women eligible for breast cancer chemoprevention.

Clinical characteristics of melanoma in an ethnically diverse population of adolescents and young adults.

e21043 Background: Melanoma is the third most common cancer among adolescents and young adults (AYAs; aged 15-39). Disease characteristics have not been well-described in this age group, particularly among diverse populations. We describe clinical features of AYAs diagnosed with melanoma at a large public hospital serving an ethnically diverse population. Methods: We reviewed medical chart data from patients diagnosed with melanoma between 2001-2016 at Los Angeles County + USC Medical Center. We describe clinical characteristics of AYA patients and compare to non-AYAs (aged ≥40) using Fisher’s exact test. A p-value &lt; 0.05 was considered statistically significant. Results: Of the 273 melanoma patients identified, 47 (17.3%) were AYAs (mean age 32.3; SD±4.45; lower age range 18). The majority of patients were Hispanic (AYA, 53.2%; non-AYA, 51.1%), followed by non-Hispanic whites (AYA, 38.3%; non-AYA, 38.7%). A greater proportion of AYA patients were female (59.6%) compared to non-AYAs (38.2%) (p &lt; 0.01). No AYA patients reported prior skin cancer compared to 19.9% of non-AYAs; 8.5% of AYAs reported family history of melanoma compared to 6.3% of non-AYAs. For all patients, superficial spreading melanoma was the most common histological subtype (AYA, 21.3%; non-AYA, 20.9%). Nodular melanoma was the second most common subtype in AYAs (17.02%) in contrast to acral lentiginous melanoma among non-AYAs (20.9%). Median Breslow depth was 3.0 mm for AYAs and 2.55 mm among non-AYAs. A slightly higher percentage of AYAs were diagnosed with regional disease (31.9%) than non-AYAs (24.4%), and a greater proportion of non-AYAs presented with distant metastases (AYA, 6.4%; non-AYA, 18.7%). The most common site of diagnosis were the extremities for all patients (AYA, 45.0%; non-AYA, 29.3%). Conclusions: We found similar clinical characteristics between AYA and non-AYA melanoma patients. However, we found a statistically significant difference for gender. The increased incidence of melanoma in female AYAs may be driven by biological factors such as sex hormones or genotype, or tanning behaviors. Further research is warranted to identify predictive and prognostic factors of melanoma among diverse AYAs, particularly females.

Attitude of Medical Students towards Psychiatry: The case of Jimma University, Southwest Ethiopia.

The inability to attract medical graduates to specialize in psychiatry has always been a serious challenge to psychiatry training programs. Therefore, the aim of this study was to assess the attitude of medical students towards psychiatry. A comparative cross-sectional survey was conducted among 122 fourth year medical students of Jimma University. The attitude of medical students towards psychiatry was measured by Attitude toward Psychiatry - 30 (ATP-30). The collected Data were analyzed by SPSS version-20 using independent samples t-test plus bivariate and multivariate logistic regression. The level of significance was determined at 95% confidence interval. Medical students who did not take psychiatry clinical rotation had a higher ATP-30 mean score 55.52(±15.2) indicating positive attitude towards psychiatry than those who completed psychiatry clinical rotation (mean= 49.75 ±10.67). Female medical students had significantly more positive attitude towards psychiatry than males (OR=9.23, 95% CI: 2.32; 36.76). Medical students who did not take psychiatry clinical rotation had more positive attitude towards psychiatry than students who completed the psychiatry clinical rotation (OR=7.58, 95% CI: 2.02; 28.37). Subjective experience of mental illness and reported family history of mental illness significantly predicted positive attitude toward psychiatry. The findings suggest that doing psychiatry rotation might have affected the attitude of medical students towards psychiatry. Future research should assess the experiential factors during psychiatry training of medical students that affect their attitudes. Also, future research needs to evaluate the attitudes of fourth year medical students before and after their psychiatry clinical rotation.

Nonfamilial Hypertrophic Cardiomyopathy: Prevalence, Natural History, and Clinical Implications.

Yield of causative variants in hypertrophic cardiomyopathy (HCM) is increased in some probands, suggesting different clinical subgroups of disease occur. We hypothesized that a negative family history and no sarcomere mutations represent a nonfamilial subgroup of HCM. We sought to determine the prevalence, natural history, and potential clinical implications of this nonfamilial subgroup of HCM. Four hundred and thirteen unrelated probands with HCM seen in a specialized HCM center between 2002 and 2015 and genetic testing performed were included in this retrospective cohort study. There were 251 (61%) probands with no reported family history of HCM, including 166 (40% of total) probands with no sarcomere mutation, that is, nonfamilial HCM. Quantified family pedigree data revealed no difference in mean number of first-degree relatives screened between nonfamilial and sarcomere-positive groups. Adjusted predictors of nonfamilial status were older age (odds ratio, 1.04; 95% confidence interval, 1.02-1.06; P=0.0001), male sex (odds ratio, 1.96; 95% confidence interval, 1.11-3.45; P=0.02), hypertension (odds ratio, 2.80; 95% confidence interval, 1.57-5.00; P=0.0005), and nonasymmetric septal morphology (odds ratio, 3.41; 95% confidence interval, 1.64-7.08; P=0.001). They had a less severe clinical course with greater event-free survival from major cardiac events (P=0.04) compared with sarcomere-positive HCM probands. Genotype prediction scores showed good performance in identifying genotype-positive patients (area under the curve, 0.71-0.75) and, in combination with pedigree characteristics, were further improved. Approximately 40% of HCM probands have a nonfamilial subtype, with later onset and less severe clinical course. We propose a revised clinical pathway for management, highlighting the role of genetic testing, a detailed pedigree, and refined clinical surveillance recommendations for family members.

Next-generation sequencing in familial breast cancer patients from Lebanon

BackgroundFamilial breast cancer (BC) represents 5 to 10% of all BC cases. Mutations in two high susceptibility BRCA1 and BRCA2 genes explain 16–40% of familial BC, while other high, moderate and low susceptibility genes explain up to 20% more of BC families. The Lebanese reported prevalence of BRCA1 and BRCA2 deleterious mutations (5.6% and 12.5%) were lower than those reported in the literature.MethodsIn the presented study, 45 Lebanese patients with a reported family history of BC were tested using Whole Exome Sequencing (WES) technique followed by Sanger sequencing validation.ResultsNineteen pathogenic mutations were identified in this study. These 19 mutations were found in 13 different genes such as: ABCC12, APC, ATM, BRCA1, BRCA2, CDH1, ERCC6, MSH2, POLH, PRF1, SLX4, STK11 and TP53.ConclusionsIn this first application of WES on BC in Lebanon, we detected six BRCA1 and BRCA2 deleterious mutations in seven patients, with a total prevalence of 15.5%, a figure that is lower than those reported in the Western literature. The p.C44F mutation in the BRCA1 gene appeared twice in this study, suggesting a founder effect. Importantly, the overall mutation prevalence was equal to 40%, justifying the urgent need to deploy WES for the identification of genetic variants responsible for familial BC in the Lebanese population.