Second-degree Relatives Of Patients Research Articles

Cohort profile: population-based cohorts of patients with colorectal cancer and of their relatives in Geneva, Switzerland

PurposeColorectal cancer (CRC) is the third leading cause of cancer death worldwide. Variability between patients in prognosis and treatment response is partially explained by traditional clinicopathological factors. We established a...

Clinical and Functional Differences Between Mexican Youth at Clinical High Risk for Psychosis and With Familial High Risk.

Few studies have explored the differences in clinical psychopathology between youth at high risk for psychosis and those at familial high risk for psychosis. This study seeks to describe and compare the sociodemographic, clinical, and functional characteristics of At-Risk Mental State (ARMS) for psychosis youth and those with a first- or second-degree relative with psychosis (Familial High-Risk: FHR) in a Mexican sample. Twenty-one ARMS individuals and 21 with FHR were evaluated for sociodemographic characteristics, psychopathological symptoms, and functional impairment. ARMS individuals were significantly younger, had fewer years of schooling, and were more likely to be male than those in the FHR group. Groups did not differ as regards marital status or occupation. The ARMS group showed greater severity of prodromal symptoms, schizotypal personality traits, and general psychopathology than the FHR group. In addition, they reported more premorbid adjustment deficit from early adolescence than the FHR group. Current overall social and role functioning was significantly lower in the ARMS group. Findings are consistent with ARMS studies from other countries. First- or second-degree relatives of patients with psychosis should be considered a vulnerable group as they display several symptoms of general psychopathology and may experience social adjustment problems in their adult lives. The lack of early detection and intervention psychosis programs in Mexico underlines the need to prioritize the development of preventive strategies to help close the care gap.

Screening for Chronic Kidney Disease in Relatives of Hemodialysis Patients

Objective: To estimate the prevalence and socioeconomic characteristics of Chronic Kidney Disease (CKD) in first and second-degree relatives of patients on hemodialysis Method: A questionnaire was applied on socioeconomic conditions, lifestyle, and personal pathological background. The formula of CKD-EPI and/or proteinuria greater than or equal to 1+ was used to characterize CKD. Analysis using the logistic regression model. Results: 408 individuals were evaluated and 12% had CKD. 6.61% had a glomerular filtration rate (GFR) ≤ 60 mL / min / 1.73 m2 and 5.39% proteinuria in the urine. The variables associated with the presence of CKD were age (OR = 1,60; 95% IC = 1,31-1,96), PAS (OR: 1,69; 95% IC: 1,24-2,28), PAD (OR: 1,52; 95% IC: 1,18- 1,96) and blood glucose (OR: 2,03; 95% IC: 1,38-2,99). Conclusion: It is necessary to implement routines for systematic evaluation that prevent or delay the loss of renal function, in addition to measures that improve the pre-dialysis clinical conditions of this population. Keywords: Chronic kidney disease, Family, Glomerular filtration rate. DOI: 10.7176/RHSS/11-10-06 Publication date: May 31 st 2021

Familial Aggregation of Childhood- and Adulthood-Onset Systemic Lupus Erythematosus.

To assess the familial occurrence of systemic lupus erythematosus (SLE) in a large Brazilian cohort. Consecutive patients with SLE were recruited and stratified according to age at disease onset into childhood-onset SLE or adult-onset SLE. Each patient was personally interviewed regarding the history of SLE across 3 generations (first-, second-, and third-degree relatives). Recurrence rates were analyzed for each degree of relation. We included 392 patients with SLE (112 with childhood-onset SLE and 280 with adult-onset SLE). We identified 2,574 first-degree relatives, 5,490 second-degree relatives, and 6,805 third-degree relatives. In the combined overall SLE cohort, we observed a familial SLE recurrence rate of 19.4 in first-degree relatives, 5.4 in second-degree relatives, and 3.0 in third-degree relatives. Recurrence rates were higher for first- and second-degree relatives of patients with childhood-onset SLE than for first- and second-degree relatives of patients with adult-onset SLE (25.2 versus 18.4 for first-degree, and 8.5 versus 4.5 for second-degree), while in third-degree relatives, recurrence rates were higher in adult-onset SLE than in childhood-onset SLE (P = 2.2 × 10-4 for differences in recurrence proportions between childhood-onset SLE and adult-onset SLE). There were no phenotypic differences in patients from multicase versus single-case families, and there was no sex-skewing observed in the offspring of patients with SLE. The greater decline in SLE recurrence rate by generation in childhood-onset SLE versus adult-onset SLE suggests a more polygenic and epistatic inheritance and suggests that adult-onset SLE may be characterized by fewer risk factors that are individually stronger. This finding suggests a higher genetic load in childhood-onset SLE versus adult-onset SLE and a difference in the genetic architecture of the disease based on age at onset.

AGA Clinical Practice Update on Young Adult–Onset Colorectal Cancer Diagnosis and Management: Expert Review

The objectives of this expert review are: (1) to prepare clinicians to recognize the presentation and evidence-based risk factors for young adult-onset colorectal cancer (CRC), defined as CRC diagnosed in individuals 18 - <50 years of age; (2) to improve management for patients with young onset CRC. This review will focus on the following topics relevant to young adult-onset CRC: epidemiology and risk factors; clinical presentation; diagnostic and therapeutic management including options for colorectal and extra-colonic surgical intervention, chemotherapy and immune-oncology therapies; genetic testing and its potential impact on preimplantation genetics; fertility preservation; and cancer surveillance recommendations for these individuals and their family members. The evidence reviewed in this manuscript is a summation of relevant scientific publications, expert opinion statements, and current practice guidelines. BEST PRACTICE ADVICE 1: With the rising incidence of people developing CRC before 50 years of age, diagnostic evaluation of the colon and rectum is encouraged for all patients, irrespective of age, who present with symptoms that may be consistent with CRC, including but not limited to: rectal bleeding, weight loss, change in bowel habit, abdominal pain, iron deficiency anemia. BEST PRACTICE ADVICE 2: Clinicians should obtain family history of colorectal and other cancers in first and second degree relatives of patients with young adult-onset CRC and discuss genetic evaluation with germline genetic testing either in targeted genes based on phenotypic presentation or in multiplex gene panels regardless of family history. BEST PRACTICE ADVICE 3: Clinicians should present the role of fertility preservation prior to cancer-directed therapy including surgery, pelvic radiation, or chemotherapy BEST PRACTICE ADVICE 4: Clinicians should counsel patients on the benefit of germline genetic testing and familial cancer panel testing in the pre-surgical period to inform which surgical options may be available to the patient with young adult-onset CRC BEST PRACTICE ADVICE 5: Clinicians should consider utilizing germline and somatic genetic testing results to inform chemotherapeutic strategies BEST PRACTICE ADVICE 6: Clinicians should offer hereditary CRC syndrome specific screening for CRC and extra-colonic cancers only to young adult-onset CRC patients who have a genetically or clinically diagnosed hereditary CRC syndrome. For patients with sporadic young adult-onset CRC, extra-colonic screening and CRC surveillance intervals are the same as for patients with older adult-onset CRC.

Impact of regular Breast Self-Examination on breast cancer size, stage, and mortality in Thailand.

Impact of regular Breast Self-Examination on breast cancer size, stage, and mortality in Thailand.

P764 Prevalence of Autoimmune diseases among first- and second-degree relatives of patients with inflammatory bowel diseases. A case–control survey in Israel

P764 Prevalence of Autoimmune diseases among first- and second-degree relatives of patients with inflammatory bowel diseases. A case–control survey in Israel

From the Editor’s Desk…: October 2018

From the Editor’s Desk…: October 2018

Melanoma risk assessment based on relatives' age at diagnosis.

The aim of this study was to determine risk for melanoma among individuals who have a first- or second-degree relative with a history of melanoma, based on the unaffected individual's age and age at diagnosis of the relative. The study employed a case-control design using a statewide database linked with a Surveillance Epidemiology and End Results cancer registry. A population-based sample of individuals who received at least one diagnosis of first primary, malignant melanoma (n = 14,281), as well as their first- and second-degree relatives, was included. Control individuals with no history of melanoma (n = 70,889) were matched to cases on birth year, gender, race/ethnicity, and county at birth. Risk for melanoma among relatives of melanoma patients declined with relative's age and age at diagnosis. Individuals between ages 40 and 49 who are first-degree relatives of melanoma patients diagnosed between ages 40 and 49 had the greatest risk for melanoma compared with individuals without a first-degree relative with a melanoma history (HR 4.89; 95% CI 3.11-7.68). Increased melanoma risk among second-degree relatives of patients was typically lower than that for first-degree relatives. Risk for melanoma, at earlier ages than expected, is increased among relatives of individuals with a history of melanoma, particularly if the melanoma case was diagnosed at a young age. Further research on the relationship between age at diagnosis and relative's melanoma risk could inform melanoma screening recommendations for individuals with a family history of the disease.

Clustering of Neuropsychiatric Disease in First-Degree and Second-Degree Relatives of Patients With Amyotrophic Lateral Sclerosis

ImportanceAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative condition primarily involving the motor system. There is increasing epidemiologic evidence of an association between ALS and a wider spectrum of neurodegenerative and neuropsychiatric disorders among family members, including schizophrenia and psychotic illness and suicidal behavior.ObjectiveTo examine the frequency and range of neuropsychiatric conditions that occur within individual first-degree and second-degree relatives of patients with ALS.Design, Setting, and ParticipantsIn this population-based, case-control family aggregation study, all 202 patients included in the Irish ALS Register between January 1, 2012, and January 31, 2014, with definite, probable, or possible ALS as defined by El Escorial criteria were invited to participate. A total of 75 patients were unable or refused to participate and were excluded; the remaining 127 patients with incident ALS were genotyped for the C9orf72 repeat expansion and 132 age- and sex-matched controls were included in the study.Main Outcome and MeasuresThe prevalence of defined neuropsychiatric disease in first-degree and second-degree relatives of patients with ALS and matched controls was determined.ResultsMean (SD) age at diagnosis of the 127 patients in the study (58 women and 69 men) was 64.2 (10.7) years. Data from 2116 relatives of patients with ALS were reported, including 924 first-degree relatives, 1128 second-degree relatives, and 64 third-degree relatives. Data from controls were reported from 829 first-degree and 1310 second-degree relatives. A total of 77 patients with ALS (61.4%) and 51 control participants (38.6%) reported at least 1 first-degree or second-degree relative with a history of schizophrenia, psychosis, suicide, depression, alcoholism, or autism (relative risk [RR], 1.50; 95% CI, 1.08-2.17; P = .02). Cluster analysis suggested the following 2 subgroups based on the number of family members with a neuropsychiatric condition: expected (0-2) and high (≥3). Within the high subgroup, ALS kindreds presented a significantly higher rate of psychiatric illness than did controls (28 of 39 [71.8%]; mean [SD] number of siblings, 4.29 [1.41]; P = .001). A strong family history of schizophrenia (RR, 3.40; 95% CI, 1.27-9.30; P = .02), suicide (RR, 3.30; 95% CI, 1.07-10.05; P = .04), autism (RR, 10.10; 95% CI, 1.30-78.80; P = .03), and alcoholism (RR, 1.48; 95% CI, 1.01-2.17; P = .045) was reported in ALS kindreds. A total of 5 of 29 probands (17.2%) with a strong family history of neuropsychiatric conditions (≥3 first-degree or second-degree relatives) carried the C9orf72 repeat expansion.Conclusions and RelevanceNeuropsychiatric symptoms in addition to schizophrenia, including obsessive-compulsive disorder, autism, and alcoholism, occur more frequently in ALS kindreds than in controls. The presence of the C9orf72 repeat expansion does not fully account for this finding, suggesting the presence of additional pleiotropic genes associated with both ALS and neuropsychiatric disease in the Irish population.

Rationale and design of a trial to personalize risk assessment in familial coronary artery disease

The lifetime risk of coronary artery disease (CAD) is doubled in people with a family history of premature disease, yet this risk is not captured in most 5- or 10-year risk assessment algorithms. Coronary artery calcium scoring (CCS) is a marker of subclinical CAD risk, which has been shown in observational studies to provide prognostic information that is incremental to clinical assessment; is relatively inexpensive; and is performed with a small radiation dose. However, the use of CCS in guiding prevention is not strongly supported by guidelines. Showing definitive evidence of the efficacy and cost-effectiveness of CCS is therefore of importance. The proposed randomized controlled trial of the use of CCS will be targeted to 40- to 70-year-old first-degree relatives of patients with CAD onset <60 years old or second-degree relatives of patients with onset <50 years old. Control patients will undergo standard risk scoring and be blinded to CCS results. In the intervention group, primary prevention in patients undergoing CCS will be informed by this score. At 3 years, effectiveness will be assessed on change in plaque volume at computed tomography coronary angiography, the extent of which has been strongly linked to outcome. The CAUGHT-CAD trial will provide evidence to inform the guidelines regarding the place of CCS in decision making regarding primary prevention of patients with a family history of premature disease.

Familial Risk in Patients With Carcinoma of Unknown Primary.

Carcinoma of unknown primary (CUP) accounts for 3% to 5% of all cancers and is associated with poor prognosis. Familial clustering of different cancer sites with CUP is unknown and may provide information regarding etiology, as well as elevated cancer risks in relatives. To quantify the risk of cancer by site in first- and second-degree relatives and first cousins of individuals with CUP. Nested case-control study of patients who received a diagnosis of CUP between 1980 and 2010 identified from the Utah Cancer Registry. Population controls with no CUP diagnosis were sex and age matched 10:1 to patients with CUP. Data about relatives were drawn from the Utah Population Database. Familial aggregation of cancer risk in relatives of cases compared with controls using Cox regression analysis. For the 4160 index patients (median [interquartile range] age, 72 [62-81] years; 47.6% male) who had received a diagnosis of CUP, first-degree relatives were at an elevated risk of CUP themselves (hazard ratio [HR], 1.35 [95% CI, 1.07-1.70]), as well as lung (HR, 1.37 [95% CI, 1.22-1.54]), pancreatic (HR, 1.28 [95% CI, 1.06-1.54]), myeloma (HR, 1.28 [95% CI, 1.01-1.62]), and non-Hodgkin lymphoma (HR, 1.16 [95% CI, >1.00-1.35]) cancers compared with controls without CUP. When the analysis was restricted to relatives of cancer-free controls, additional increased risks for colon (HR, 1.19 [95% CI, 1.06-1.33]) and bladder (HR, 1.18 [95% CI, >1.00-1.38]) cancers were observed. Second-degree relatives of patients with CUP were at a slight increased risk of lung (HR, 1.14 [95% CI, 1.03-1.26]), pancreatic (HR, 1.17 [95% CI, 1.01-1.37]), breast (HR, 1.09 [95% CI, 1.02-1.16]), melanoma (HR, 1.09 [95% CI, >1.00-1.19]), and ovarian (HR, 1.19 [95% CI, 1.02-1.39]) cancers. Relatives of patients with CUP are at increased risk of CUP and several other malignant neoplasms, including lung, pancreatic, and colon cancer. The present data may suggest sites of origin for CUP and provide cancer risk information for relatives of patients with CUP that can lead to effective intervention. Relatives of patients with CUP should be aware of the elevated risks for lung, pancreatic, and colon cancer and encouraged to modify risk factors and adhere to site-specific population cancer screening.

Multiplexed autoantigen microarrays identify HLA as a key driver of anti-desmoglein and -non-desmoglein reactivities in pemphigus

Patients with pemphigus vulgaris (PV) harbor antibodies reactive against self-antigens expressed at the surface of keratinocytes, primarily desmoglein (Dsg) 3 and, to a lesser extent, Dsg1. Conventionally, only antibodies targeting these molecules have been thought to contribute to disease pathogenesis. This notion has been challenged by a growing pool of evidence that suggests that antibodies toward additional targets may play a role in disease. The aims of this study were to (i) establish high-throughput protein microarray technology as a method to investigate traditional and putative autoantibodies (autoAbs) in PV and (ii) use multiplexed protein array technology to define the scope and specificity of the autoAb response in PV. Our analysis demonstrated significant IgG reactivity in patients with PV toward the muscarinic acetylcholine receptor subtypes 3, 4, and 5 as well as thyroid peroxidase. Furthermore, we found that healthy first- and second-degree relatives of patients with PV express autoAbs toward desmoglein and non-Dsg targets. Our analysis also identified genetic elements, particularly HLA, as key drivers of autoAb expression. Finally, we show that patients with PV exhibit significantly reduced IgM reactivity toward disease-associated antigens relative to controls. The use of protein microarrays to profile the autoAb response in PV advanced the current understanding of disease and provided insight into the complex relationship between genetics and disease development.

The Occurrence of Occult Acetabular Dysplasia in Relatives of Individuals With Developmental Dysplasia of the Hip.

This study sought to determine the hip pathology of family members of patients with developmental dysplasia of the hip (DDH). The authors evaluated 120 people from 19 families known to have at least 1 member with surgically treated DDH. Each individual's functional outcome scores and pelvic radiographs were assessed for hip symptoms or pathology. Using a genetic population database and a pediatric hospital patient population, 19 families with high rates of DDH were identified. All family members (n=120) underwent physical examination, radiographic assessment, and completion of outcome instruments [American Academy of Orthopedics (AAOS) Hip and Knee; Harris Hip Score (HHS); and Western Ontario and McMaster Universities Arthritis Index (WOMAC)]. The 120 subjects ranged from 1 to 84 years, 34 had orthopaedically treated DDH. Of the remaining 86 supposedly normal subjects, 23 (27%) had occult acetabular dysplasia (OAD) as defined by center edge angle (CEA) <20 and/or a Severin score of III or greater. Sixty percent of the 86 individuals were less than 30 years old, 74% of the OAD group were less than 30. Outcome scores of the treated DDH patients (AAOS, HHS, and WOMAC) were worse on the involved side regardless of age. Over age 30 individuals with OAD had statistically significant decreases in their AAOS Hip and Knee and WOMAC scores on the dysplastic side, but their HHS scores were not significantly different. Twenty-seven percent of first-degree and second-degree relatives of patients with DDH had unsuspected radiographic acetabular dysplasia in our study. Most of the subjects with OAD were younger than 30. After age 30, many of these patients developed symptoms. In families with a significant history of DDH, radiographic screening of siblings of patients with DDH to define OAD may be prudent. Level I—diagnostic study.

Risk of Celiac Disease in the First- and Second-Degree Relatives of Patients With Celiac Disease: A Systematic Review and Meta-Analysis.

First-degree relatives (FDRs) of patients with celiac disease (CD) are at high risk for CD and prevalence among them varies from 1.6 to 38%. The risk of having CD among FDRs if the FDR is sister, brother, mother, father, son, or daughter of index patient with CD is not known. We conducted a meta-analysis and calculated pooled prevalence of CD among FDRs, second-degree relatives (SDRs), and specific relations with index patient. On search of literature, 2,259 articles appeared of which 54 articles were included in this meta-analysis. Diagnosis of CD was based on standard criteria. Pooled prevalence of CD was 7.5% (95% confidence interval (CI) 6.3%, 8.8%) in 10,252 FDRs and 2.3% (95% CI 1.3%, 3.8%) in 642 SDRs. Pooled prevalence of CD was highest in siblings (8.9%), followed by offsprings (7.9%) and parents (3.0%). Female FDRs had higher prevalence than male FDRs (8.4% vs. 5.2%, P=0.047). While sisters and daughters of index patient had the highest risk of having CD (1 in 7 and 1 in 8, respectively), the risk was 1 in 13 in sons, 1 in 16 in brothers, 1 in 32 in mothers, and 1 in 33 in fathers. There were also differences in the pooled prevalence of CD in FDRs according to their geographic location. Pooled prevalence of CD among FDRs is 7.5% and varies considerably with their relationship with the index patient. The risk of CD in FDRs also varies according to gender and geographical location.

Sa1290 Risk of Celiac Disease in the First and Second Degree Relatives of Patients With Celiac Disease: A Meta-Analysis

Sa1290 Risk of Celiac Disease in the First and Second Degree Relatives of Patients With Celiac Disease: A Meta-Analysis

Family patterns of psychopathology in psychiatric disorders

ObjectiveFamilial loading and crucial outcomes of family history of psychopathology in psychiatric disorders have long been recognized. There has been ample literature providing convincing evidence for the importance of family psychopathology in development of emotional disturbances in children as well as worse outcomes in the course of psychiatric disorders. More often, maternal psychopathology seems to have been an issue of interest rather than paternal psychopathology while effects of second-degree familiality have received almost no attention. In this study, we addressed the relations between affected first- and second-degree relatives of probands and categories of psychiatric disorders. MethodSubjects were 350 hospitalized psychiatric inpatients, consecutively admitted to psychiatry clinics in Van, Turkey. Mean age was 34.16 (SD±12) and 51.4% of the sample consisted of male patients. Assessment of psychopathology in psychiatric probands was conducted based on DSM-IV TR. Familial loading of psychiatric disorders amongst first- and second-degree relatives of patients were initially noted primarily relying on patients' retrospective reports, and confirmed by both phone call and following official health records via the Medical Knowledge System. We analyzed the data using latent class analysis approach. ResultsWe found four patterns of familial psychopathology. Latent homogeneous subsets of patients due to familial characteristics were as paternal kinship psychopathology with schizophrenia, paternal kinship psychopathology with mood disorders, maternal kinship psychopathology and core family psychopathology. ConclusionFamily patterns were critical to exerting variation in psychiatric disorders of probands and affected relatives. Probands with a core family pattern of psychopathology exhibited the most colorful clinical presentations in terms of variation in psychopathology. We observed a specificity of intergenerational transmission of psychiatric disorders when family patterns of psychopathology were taken into consideration, even second-degree relatives of psychiatric probands.

Issue Highlights

Issue Highlights

Familial Clustering of Barrett's Esophagus and Esophageal Adenocarcinoma in a European Cohort

Up to 7% of cases of Barrett's esophagus (BE) or esophageal adenocarcinoma (EAC) in the United States occur in family clusters. We identified first-degree and second-degree relatives of patients with BE and EAC to determine the extent of familial clustering in a European cohort and studied differences between familial and nonfamilial cases. A questionnaire was sent to all patients diagnosed with BE or EAC from 2000-2011 at 3 hospitals in the Netherlands (n = 838). Diagnoses of affected relatives were confirmed by using the Dutch Pathology Registry. Familial statuses of BE were defined as definitive (≥1 first-degree or second-degree relative with BE or EAC), possible (≥1 reported relative with BE or esophageal cancer without histologic confirmation), unlikely (no family history), or unknown. A total of 603 patients with BE or EAC (71%) responded and were included in the analysis. Familial BE was definitive for 7% of cases (n = 39, 10% of first-degree relatives affected), possible for 6% (n = 36), unlikely for 49% (n = 297), and unknown for 38% (n = 231). Definitive cases of familial BE were younger at onset of heartburn and EAC diagnosis; their first-degree relatives more frequently had reflux symptoms and a prior upper endoscopy, compared with unlikely cases of familial BE. In a database analysis of patients diagnosed with BE or EAC in the Netherlands, 7% of cases of BE and EAC were familial. These cases have a younger average age of onset of reflux symptoms and diagnosis of EAC than unlikely familial cases. These findings may indicate that genetic factors contribute to BE susceptibility, with a possible central role of gastroesophageal reflux.

Evaluation of Breast Self-Examination (BSE) Application in First and Second Degree Relatives of Patients with Breast Cancer

The aim of this study was to determine beliefs concerning breast self-examination in first- and second-degree relatives of patients with breast cancer and evaluate their breast self-examination (BSE) application. A survey study was conducted in an oncology polyclinic and general surgery clinic of a hospital in Ankara, the capital of Turkey with a sample of 140 women. It was determined that 60.7% of the participants had conducted BSE and 48.1% had undergone a clinical breast examination. Perceived self- efficacy of the women who performed BSE were significantly higher compared with women who did not practice BSE (p<0.001) Furthermore, perceived barriers were lower among those who had performed BSE (p<0.001). Logistic regression analysis indicated that women who perceived higher self-efficacy (OR: 1.119, 95% CI: 1.056- 1.185, p<0.001) and had regular CBE (OR: 8.250, 95% CI: 3.140-21.884, p<0.001) and educational status (OR: 5.287, 95% CI: 1.480-18.880, p<0.01) were more likely to perform BSE. Findings from this study indicated that perceived barriers, perceived self-efficacy, and educational status could be predictors of BSE behavior among the first- and second-degree relatives of patients with breast cancer. Therefore, BSE training programs that emphasize self-efficacy and address perceived barriers are recommended.