Association between family history and lung cancer risk among Chinese women in Singapore

Risk factors of lung cancer unrelated to smoking are not well-studied, especially among women. Family history has been shown to play a role in predisposing individuals to lung cancer, but this relationship has not been investigated in the Southeast Asian population. A total of 1159 women were recruited in a case–control study conducted in public hospitals in Singapore from 2005 to 2008. After excluding participants with incomplete family history information, 374 cases and 785 controls remained in the final analysis. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated using logistic regression, adjusting for potential confounders. Overall, family history of lung cancer was associated with a higher risk for lung cancer (aOR 2.08, 95% CI 1.25–3.47). When stratified by smoking status, a significant association was observed among never-smokers (aOR 2.78, 95% CI 1.57–4.90). Further stratification by fruit consumption identified a significant association between family history of lung cancer and higher risk of lung cancer among never-smokers who had low fruit consumption (aOR 3.09, 95% CI 1.37–7.01). Our findings suggest that family history of lung cancer is a significant risk factor for lung cancer in Singaporean Chinese women, especially among never-smokers.

Variant location is a novel risk factor for individuals with arrhythmogenic cardiomyopathy due to a desmoplakin (DSP) truncating variant

Background: Truncating variants in desmoplakin (DSPtv) are an important cause of arrhythmogenic cardiomyopathy (ACM), however the genetic architecture and genotype-specific risk factors are incompletely understood. We evaluated phenotype, risk factors for ventricular arrhythmias, and underlying genetics of DSPtv cardiomyopathy. Methods: Individuals with DSPtv and any cardiac phenotype, and their gene-positive family members were included from multiple international centers. Clinical data and family history information were collected. Event-free survival from ventricular arrhythmia was assessed. Variant location was compared between cases and controls, and literature review of reported DSPtv performed. Results: There were 98 probands and 72 family members (mean age at diagnosis 43 +/- 18 years, 59% female) with a DSPtv, of which 146 were considered clinically affected. Ventricular arrhythmia (sudden cardiac arrest, sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator therapy) occurred in 56 (33%) individuals. DSPtv location and proband status were independent risk factors for ventricular arrhythmia, while prior risk factors showed no association. Further, gene region was important with variants in cases (cohort n=98, Clinvar n=168) more likely to occur in the regions resulting in nonsense mediated decay of both major DSP isoforms, compared to n=124 gnomAD control variants (148 [83.6%] versus 29 [16.4%], p<0.0001). Conclusions: In the largest series of individuals with DSPtv, we demonstrate variant location is a novel risk factor for ventricular arrhythmia, can inform variant interpretation, and provide critical insights to allow precision-based clinical management.

Synthetic data for annotation and extraction of family history information from clinical text

Background The limited availability of clinical texts for Natural Language Processing purposes is hindering the progress of the field. This article investigates the use of synthetic data for the annotation and automated extraction of family history information from Norwegian clinical text. We make use of incrementally developed synthetic clinical text describing patients’ family history relating to cases of cardiac disease and present a general methodology which integrates the synthetically produced clinical statements and annotation guideline development. The resulting synthetic corpus contains 477 sentences and 6030 tokens. In this work we experimentally assess the validity and applicability of the annotated synthetic corpus using machine learning techniques and furthermore evaluate the system trained on synthetic text on a corpus of real clinical text, consisting of de-identified records for patients with genetic heart disease. Results For entity recognition, an SVM trained on synthetic data had class weighted precision, recall and F1-scores of 0.83, 0.81 and 0.82, respectively. For relation extraction precision, recall and F1-scores were 0.74, 0.75 and 0.74. Conclusions A system for extraction of family history information developed on synthetic data generalizes well to real, clinical notes with a small loss of accuracy. The methodology outlined in this paper may be useful in other situations where limited availability of clinical text hinders NLP tasks. Both the annotation guidelines and the annotated synthetic corpus are made freely available and as such constitutes the first publicly available resource of Norwegian clinical text.

The Most Important Risk Factors Among Angina Patients in Thi-Qar Governorate in Iraq

Angina is a chest pressure, discomfort, or pain like a squeeze. It may occur as an angina attack that typically lasts from 1 to 15 minutes; however, angina is not only a disorder, but is also a symptom of heart disease. There are various risk factors that lead to raising an angina pectoris attack which were designated in previous studies but no one detected the most significant one in Thi- Qar governorate. Because of the specific economic, lifestyle and environment characteristics of this governorate, the present study has aimed to determine the most important risk factors that trigger angina among patients of the Nasiriya Heart Center in Nasiriya city. A cross-sectional study has been conducted in Nasiriya Heart Center which involved 200 angina patients that attended the hospital. The patients answered questioners’ form that has been designed by the researcher. The collecting data contained the demographic, lifestyle and family history information of patients. The results showed no significant differences between male and female in angina occurrence. An age group 31- 60 year was considered the most susceptible to the incidence of angina. However, no significant impacts of the genetic, smoking, alcohol and obesity were found as risk factors. On the other hand, significant effects of diabetes, hypertension, eating habits and stress in the angina incidence were determined. In conclusion, the specificity of the governorate has had the greatest impact on the determination of risk factors where, apart from eating habits, the stress in its various types was the most important factor; therefore, intensive studies must promote population health conditions in this governorate.

High Familial Recurrence of Congenital Heart Defects in Laterality Defects Patients: An Evaluation of 184 Families

As a rare disease with genetic pathogenesis, observational study about familial CHD recurrence risk on CHD patients with laterality defects is lacking. This study aimed to investigate familial recurrence among families of patients with CHD and laterality defects, and compare them with CHD patients without laterality defects. A total of 184 patients with CHD and laterality defects treated in Cardiovascular Center, Children’s Hospital of Fudan University were observed from 2008 to 2019. A detailed family history was documented by trained staff using questionnaires, and information about the subtypes of CHD and laterality defects was also collected. In addition, positive family history information, including all three degrees relatives and all affected family members, was reconfirmed by trained medical staff through face-to-face interviews, telephone interviews, and letter return visits. Of the 184 included patients, 30 had at least one family member (from among three linear generations and distant relatives) with CHD. The familial recurrence rate of CHD in our cohort was 16.3% (30/184), which was higher than the 3.3% (67/2024) of patients with CHD without laterality defects. This result shows that the recurrence rate among the first-, second-, and third-degree relatives was 11.7% (11/94), 1.5% (3/204), and 3.1% (6/91) and that the recurrence rate among siblings (21.4%, 9/42) was higher than that among parents (3.8%, 2/52). The familial recurrence risk of CHD among patients with CHD and laterality defects is high, which is consistent with the previous study that reported a high familial recurrence of heterotaxy of 10%. First-degree relatives have a higher recurrence rate than second- and third-degree relatives, especially siblings. These findings have important significance for prenatal screening, intervention, and genetic counseling in the Chinese population, but may not be generalizable to other populations that may have different rates of familial and sporadic cases.

Use of the Utah population database to evaluate statewide use of genetic testing for hereditary breast/ovarian cancer.

e22529 Background: Genetic testing for hereditary breast/ovarian cancer (HBOC) continues to be underutilized, and options for population-based assessment of testing barriers and outcomes are lacking. This project uses linkages between statewide data sources available through the Utah Population Database (UPDB) to establish an infrastructure for studying the use of HBOC cancer genetic testing across a state. Methods: Clinical HBOC testing data from 1994-2018 was obtained for the University of Utah Huntsman Cancer Institute, Intermountain Healthcare, Utah Cancer Specialists, and the Salt Lake Veterans administration via electronic imports of tests attributed to these healthcare systems from three commercial laboratories. Genetic testing was linked to external data through the UPDB to determine demographic and urban/rural designation. Cancer diagnoses were obtained from the Utah Cancer Registry, and genealogies from the Utah Resource for Genetic and Epidemiology Research. These variables were matched to data available for the individual at the date of testing. For individuals with multiple genetic tests, the date for the first test was used. Results: Testing data was available for 12983 individuals who linked to additional records within the UPDB. Tested individuals were 86% White, 9% Hispanic, and 16% lived in rural/frontier areas. 75% of tests were performed between 2011-2018. 1575 (12%) had >1 pathogenic variant (PVs) identified in an HBOC gene, with the majority of PVs being in BRCA1/2 (89%), and TP53, CHEK2, and ATM each accounting for 2% of PVs. 7178 cancers were diagnosed in 5980 individuals (46%, avg. 1.2 cancer/person). Cancer cases were evaluated to determine if National Comprehensive Cancer Network (HBOC 2018) criteria were met. Cancer cases who have a relative with BC < 50 years of age or a relative with ovarian cancer (OC) were more likely to have a have BRCA1/2 PV than cases not meeting those criteria (17.5% vs 6.1% and 22.3% vs. 6.3% respectively). Cancer cases meeting criteria due to family history of pancreatic cancer also had a higher rate of PVs (13.1% vs. 8.4%) predominately due to additional PVs in BRCA2. Conclusions: This project begins to address the challenge of population assessment of HBOC genetic testing. We established a regulatory infrastructure to share testing data between multiple healthcare systems. In collaboration with commercial laboratories, genetic testing data was obtained in a consistent, discrete format even though it is stored differently within each health care system. The majority (54%) of HBOC testing in Utah is happening in people who did not have cancer at the time of their test, and focusing on assessing testing of cancer patients will not provide comprehensive information on testing done in the state. Among individuals with cancer, access to family history information is crucial for assessing the rate of PVs and utility of testing criteria.

Correction: Extracting Family History Information From Electronic Health Records: Natural Language Processing Analysis (Preprint)

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Essential Tremor Families With Heterogeneous Motor Phenomenology: “Mixed Motor Disorder”

Objective:Essential tremor (ET) is one of the most prevalent movement disorders. Because ET is so common, individuals with other neurological disorders may also have ET. There is evidence, however, that the co-occurrence of ET with Parkinson’s disease (PD) and/or dystonia is not merely a chance co-occurrence. We have observed combinations of these three movement disorders within individuals and across individuals within families containing multiple individuals with ET. This observation has a number of implications. Our objective is to present four ET families in whom motor phenomenology was heterogeneous, and discuss the implications of this finding.Methods:ET cases and their relatives were enrolled in the Family Study of Essential Tremor (2015 – present). Phenotyping was performed by a senior movement disorders neurologist based on neurological examination.Results:We present four families, including 14 affected individuals, among whom assigned diagnoses were ET, PD, ET + PD, and ET + dystonia. In those with ET and another movement disorder, the predominant and earliest phenotype was ET.Conclusion:There are assortments of these three involuntary motor disorders, ET, dystonia and PD, both within individuals and in different individuals within ET families. This observation has mechanistic implications. Furthermore, we believe the concept of the “mixed motor disorder” should enter into and inform the clinical dialogue. In assigning diagnoses, clinicians are swayed by family history information, and they should be prepared a mix of different motor disorders to manifest within particular families.