Family History Interview Research Articles

Familial aggregation of idiopathic normal pressure hydrocephalus: Novel familial case and a family study of the NPH triad in an iNPH patient cohort

ObjectiveIdiopathic normal pressure hydrocephalus (iNPH) is considered sporadic, yet familial cases involving single pedigrees are being increasingly recognized. As current evidence does not extend beyond isolated pedigrees, we aimed to determine the putative heritability of iNPH by examining the prevalence of the iNPH triad among the family members of iNPH probands. MethodWe present a case–control family study of the iNPH symptom triad among the relatives of iNPH patients (n=20) identified from a cohort of patients undergoing CSF diversion and matched comparison subjects (n=21). A total of 291 first-degree relatives from 41 families were characterized using semi-structured family history interviews. Independent from the family study, we present a novel well-characterized familial case of iNPH. Results≥2 insidious, progressive and idiopathic iNPH symptoms were identified among first degree relatives in 6 iNPH pedigrees (2 multiply affected) and 1 control pedigree, with an incidence of 7.1% among iNPH relatives and 0.7% among control relatives (OR=11.53). Gait disturbance and memory impairment began at a younger age among the relatives of iNPH probands. Independent of our family study, we present a novel case report of a large iNPH pedigree with multiple affected relatives. InterpretationOur family study and novel familial case suggest familial aggregation of iNPH. A larger family study with full characterization of affected and unaffected relatives is warranted. Confirmation of heritability may allow identification of individuals at high-risk for iNPH, early intervention, and improved aetiological elucidation.

Expression of the Broad Autism Phenotype in Simplex Autism Families from the Simons Simplex Collection

The broad autism phenotype (BAP) refers to the phenotypic expression of an underlying genetic liability to autism, manifest in non-autistic relatives. This study examined the relationship among the Broad Autism Phenotype Questionnaire (BAPQ), Social Responsiveness Scale: Adult Research Version (SRS:ARV), and Family History Interview (FHI) in a large, multi-site study of 1,650 simplex families (Simons Simplex Collection). Correlations between the BAPQ and SRS:ARV Total scores were moderate, and correlations between FHI ratings and SRS:ARV and BAPQ were significant but weak. Overall, the results suggested that BAP traits occur at low rates in simplex families, and rates vary significantly depending upon the measure utilized. Implications include the need for multiple informants, and the assessment of distinct BAP traits in large-scale genetic studies of individuals with ASD.

The Influence of Informant Characteristics on the Reliability of Family History Interviews

Family history interviews are widely used in psychiatric research, as well as in genetic and twin studies, and provide a way to collect family history information quickly and economically. To obtain a valid assessment of family history, it is important to investigate which family member will be able to provide accurate information. Previous research shows that the validity of family history reporting can be influenced by characteristics of the informant, such as age, gender and personal history of psychiatric disorder. The aim of this study was to investigate the role of a subject's position in a pedigree on the validity of data collection. Family history data on diabetes and psychiatric disorders were collected in three generations of 33 families by interviewing both an index subject (3rd generation) and his or her mother (2nd generation). Mothers were shown to report higher rates of diabetes and psychiatric disorder in the family compared to the index subjects. There was no significant difference in the disease rate reported by male and female index subject. Mothers who experienced a depressive episode indicated significantly more family members as having a psychiatric disorder than mothers who never experienced such an episode. This could be explained by the presence of informant bias, but may also result from the fact that depression is a heritable disorder and is therefore actually more prevalent in these families. Our findings suggest that family interview data should be collected by interviewing subjects who have a central position in the pedigree and can therefore provide information on his/her own generation, the previous and the next. In addition, psychiatric status of the informant should be carefully addressed.

Personal and family history of suicidal behaviour is associated with lower peripheral cortisol in depressed outpatients

BackgroundSuicidal behaviour aggregates in families and HPA-axis dysregulation may help explain part of this familial aggregation. Nevertheless, exogenous manipulation of the HPA-axis has yielded mixed results. Naturalistic and non-pharmacological inductions of the HPA-axis do not suggest hyper-responsiveness, yet suggest greater cognitive consequences of stress in individuals at risk for suicide. In this study, we aimed to characterize the relationship between plasma cortisol and an increased risk for suicide, as defined by family history. MethodPatients (N=148) with depressive disorders underwent psychopathological assessment, including structured investigation of past suicidal behaviour and underwent laboratory blood testing of cortisol. They also completed a family history interview investigating family psychopathology and suicidal behaviour, representing data on 848 first degree relatives. The relationship between plasma cortisol, past suicidal behaviour and suicidal behaviour among first degree relatives was examined. ResultsLower levels of plasma cortisol were associated with a personal and family history of suicidal behaviour, as well as a family history of depression among first degree relatives. Multivariate analyses controlling for significant psychopathology replicated the association between lower levels of plasma cortisol, a family history of suicidal behaviour and personal history of suicide attempts, but not a family history of depression. Controlling for personal history of suicide attempts revealed an independent association between plasma cortisol and family history of suicidal behaviour, with an additional contribution by family history of depression in predicting the latter. ConclusionsLower plasma cortisol is associated with a family history of suicide among depressed outpatients, independent of psychopathology and previous suicide attempts.

Frequency of Known Mutations in Early-Onset Parkinson Disease

To assess the frequency and clinical characteristics of carriers of previously identified mutations in 6 genes associated with early-onset Parkinson disease (PD) and provide empirical data that can be used to inform genetic counseling. Cross-sectional observational study. Thirteen movement disorders centers. Nine hundred fifty-three individuals with early-onset PD defined as age at onset (AAO) younger than 51 years. Participants included 77 and 139 individuals of Hispanic and Jewish ancestry, respectively. Intervention Mutations in SNCA, PRKN, PINK1, DJ1, LRRK2, and GBA were assessed. A validated family history interview and the Unified Parkinson Disease Rating Scale were administered. Demographic and phenotypic characteristics were compared among groups defined by mutation status. Main Outcome Measure Mutation carrier frequency stratified by AAO and ethnic background. One hundred fifty-eight (16.6%) participants had mutations, including 64 (6.7%) PRKN, 35 (3.6%) LRRK2 G2019S, 64 (6.7%) GBA, and 1 (0.2%) DJ1. Mutation carriers were more frequent in those with an AAO of 30 years or younger compared with those with AAO between 31 and 50 years (40.6% vs 14.6%, P < .001), in individuals who reported Jewish ancestry (32.4% vs 13.7%, P < .001), and in those reporting a first-degree family history of PD (23.9% vs 15.1%, P = .01). Hispanic individuals were more likely to be PRKN carriers than non-Hispanic individuals (15.6% vs 5.9%, P = .003). The GBA L444P mutation was associated with a higher mean Unified Parkinson Disease Rating Scale III score after adjustment for covariates. Individuals of Jewish or Hispanic ancestry with early-onset PD, those with AAO of 30 years or younger, and those with a history of PD in a first-degree relative may benefit from genetic counseling.

Maternal depressive symptoms, and not anxiety symptoms, are associated with positive mother–child reporting discrepancies of internalizing problems in children: a report on the TRAILS Study

Maternal internalizing problems affect reporting of child’s problem behavior. This study addresses the relative effects of maternal depressive symptoms versus anxiety symptoms and the association with differential reporting of mother and child on child’s internalizing problems. The study sample comprised a cohort of 1,986 10- to 12-year-old children and their mothers from the Dutch general population in a cross sectional setup. Children’s internalizing problems were assessed with the DSM-IV anxiety and affective problem scales of the Child Behavior Checklist (CBCL) and the Youth Self-Report (YSR). Current maternal internalizing problems were assessed with the depressive and anxiety symptom scales of the Depression Anxiety Stress Scale (DASS), while the TRAILS Family History Interview (FHI) measured lifetime maternal depression and anxiety. Results show that current and lifetime maternal depressive symptoms were associated with positive mother–child reporting discrepancies (i.e. mothers reporting more problems than their child). Considering the small amount of variance explained, we conclude that maternal depressive symptoms do not bias maternal reporting on child’s internalizing problems to a serious degree. Studies concerning long term consequences of mother–child reporting discrepancies on child’s internalizing problems are few, but show a risk for adverse outcome. More prognostic research is needed.

Munchausen Syndrome by Proxy: A Dilemma for Diagnosis

Very little is yet known about the etiology, epidemiology, and long-term impact of Munchausen syndrome by proxy (MSBP). However, on reviewing the literature, there is an increasing interest in this unusual but serious pathology, which appears almost always in children and poses many clinical and forensic dilemmas for diagnosis and management. We present a MSBP case-study of a mother (54 years old) and her son (13 years old), through their Rorschach tests (Comprehensive System; Exner, 2000 ) and the Research Diagnostic Criteria Family-History interview (FH-RDC; Endicott, Andreasen &amp; Spitzer, 1989 ). The main objectives were (1) to compare psychological evaluation data with DSM-IV-TR criteria for Personality Disorder (PD), and (2) to describe MSBP psychopathological manifestations on both records. Since it is a case-study, Rorschach variables were analyzed in two ways: (1) parametric variables were standardized with respect to the norms for each age and then zscores were used, and (2) nonparametric variables and some formulations were dichotomized in order to use the critical scores proposed by Exner (2000 ). Results confirm the presence of a PD in the mother. In the boy, they indicate that we could expect a development toward a PD or an increase of his isolation and his perceptual-cognitive disarray, with a possible long-term split of his frail psychic balance.

Psychiatrische Erkrankungen bei Verwandten von Patienten mit Anorexia nervosa und Bulimia nervosa

Family studies of anorexia (AN) and bulimia (BN) nervosa in relatives of patients with eating disorders compared to control subjects are rare in German-speaking countries. A German multicenter study compared first-, second- and third-degree relatives of 65 adolescent AN subjects (n = 746), 21 adolescent BN subjects (n = 265) and relatives of 11 adolescent depressive control subjects (n = 157), as well as those of 37 adolescent healthy control subjects (n = 480). Assessments included the Diagnostic Interview for Genetic Studies (DIGS), the short form of the Family Interview of Genetic Studies (FIGS), and the Eating Disorder Family History Interview. Rates of anorexia nervosa and major depressive disorder (trend) were significantly (p < .01) higher among the first- and second-degree relatives of anorexic and bulimic subjects than among the relatives of healthy controls. Most results were more prominent among relatives of bulimic index patients. Nevertheless, the frequencies were lower in this sample than in comparable US-American samples. The data confirm the hypothesis of familial vulnerability to anorexia and bulimia nervosa. The observed differences in comorbidity patterns among eating-disordered relatives may be due to an age effect of the index patients.

Variability in adaptive behavior in autism: evidence for the importance of family history.

Adaptive behavior in autism is highly variable and strongly related to prognosis. This study explored family history as a potential source of variability in adaptive behavior in autism. Participants included 77 individuals (mean age = 18) with average or better intellectual ability and autism. Parents completed the Family History Interview about the presence of broader autism phenotype symptoms and major psychiatric disorders in first degree relatives. Adaptive behavior was assessed via the Vineland Adaptive Behavior Scales (VABS). Based on family history variables, age, and intelligence quotient (IQ), 87% of participants were correctly classified as having impaired or average VABS scores. Family history of depression and shyness accounted for the most variance in VABS scores, and they had the greatest influence on VABS Socialization scores in particular. Possible underlying mechanisms include genetics, psychosocial factors, and social resources. This study provides initial evidence of the importance of family history to adaptive behavior in autism and has implications for genetics and treatment.

Predicting Prognosis for the Conduct-Problem Boy: Can Family History Help?

Many children with conduct disorder develop life-course persistent antisocial behavior; however, other children exhibit childhood-limited or adolescence-limited conduct disorder symptoms and escape poor adult outcomes. Prospective prediction of long-term prognosis in pediatric and adolescent clinical settings is difficult. Improved prognosis prediction would support wise allocation of limited treatment resources. The purpose of this article is to evaluate whether family history of psychiatric disorder can statically predict long-term prognosis among conduct-problem children. Participants were male members of the Dunedin Study, a birth cohort of 1,037 children (52% male). Conduct-problem subtypes were defined using prospective assessments between ages 7 and 26 years. Family history interviews assessed mental disorders for three generations: the participants' grandparents, parents, and siblings. Family history of externalizing disorders distinguished life-course persistent antisocial males from other conduct-problem children and added significant incremental validity beyond family and child risk factors. A simple three-item family history screen of maternal-reported alcohol abuse was associated with life-course persistent prognosis in our research setting and should be evaluated in clinical practice. : Family history of externalizing disorders distinguished between life-course persistent versus childhood-limited and adolescent-onset conduct problems. Brief family history questions may assist clinicians in pediatric settings to refine the diagnosis of conduct disorder and identify children who most need treatment.

Turkish Family Narratives: The Relationships between Mothers- and Daughters-in-Law

Through an analysis of eighteen family history interviews conducted with elderly women from Istanbul, this article examines the nature of the relationships between mothers- and daughters-in-law in Turkey between 1923 and the 1940s. This period marks the foundation of the republic and the Kemalist reforms that transform the way of life in society. The theory of narrative identity and the definition of family as a group of people who narrate the same story from generation to generation form the backbone of this study. The main themes of the interview data point out a kind of power relationship similar to Foucault's understanding of power and its use in everyday life. Thus, a social constructionist/hermeneutic position is adopted which integrates seemingly different theoretical conceptualizations like narrative identity, Foucault's concept of power, and Bourdieu's concepts of economic and cultural capital.

A family study of co-morbidity between generalized social phobia and generalized anxiety disorder in a non-clinic sample

BackgroundHigh rates of co-morbidity between Generalized Social Phobia (GSP) and Generalized Anxiety Disorder (GAD) have been documented. The reason for this is unclear. Family studies are one means of clarifying the nature of co-morbidity between two disorders. MethodsSix models of co-morbidity between GSP and GAD were investigated in a family aggregation study of 403 first-degree relatives of non-clinical probands: 37 with GSP, 22 with GAD, 15 with co-morbid GSP/GAD, and 41 controls with no history of GSP or GAD. Psychiatric data were collected for probands and relatives. Mixed methods (direct and family history interviews) were utilised. ResultsPrimary contrasts (against controls) found an increased rate of pure GSP in the relatives of both GSP probands and co-morbid GSP/GAD probands, and found relatives of co-morbid GSP/GAD probands to have an increased rate of both pure GAD and co-morbid GSP/GAD. Secondary contrasts found (i) increased GSP in the relatives of GSP only probands compared to the relatives of GAD only probands; and (ii) increased GAD in the relatives of co-morbid GSP/GAD probands compared to the relatives of GSP only probands. LimitationsThe study did not directly interview all relatives, although the reliability of family history data was assessed. The study was based on an all-female proband sample. The implications of both these limitations are discussed. ConclusionsThe results were most consistent with a co-morbidity model indicating independent familial transmission of GSP and GAD. This has clinical implications for the treatment of patients with both disorders.

Validation of a Self-Administered, Computerized Tool for Collecting and Displaying the Family History of Cancer

A detailed family history is important for cancer risk assessment, but obtaining it is time consuming and infrequently accomplished in practice. The Genetic Risk Easy Assessment Tool (GREAT) conducts a computer-administered family history interview and immediately generates a pedigree diagram in digital form. The purpose of this study was to validate family cancer histories produced by patients using the computer tool in comparison with pedigrees made by genetic counselors. Patients scheduled for genetics consultation recorded their family histories using the GREAT, separate from their genetic counseling session. The presence of each relative; presence, type, and age at diagnosis of cancers; and cancer geneticist's risk assessment were compared for 120 pairs of pedigrees produced by counselors versus computer tool. The automated telephone interview took a mean of 33.5 minutes and was highly acceptable to respondents. Ninety-four percent of first-degree relatives, 67% of second-degree relatives, and 38% of third-degree relatives were identical on paired pedigrees; computer-generated pedigrees included additional relatives. Sixty-three percent of all cancers were identified by both family histories, with 90% agreement on the type of cancer. There was very good agreement (kappa = 0.70; correlation = 0.77) between the geneticist's breast cancer risk assessments based on computer versus counselors' pedigrees. In a subsample of 61 users, test-retest reliability for the computer-administered questionnaire was high (phi = 0.94 for cancers in first-degree and phi = 0.91 in second-degree relatives). The GREAT computer-administered questionnaire provides an acceptable, reliable, and valid way of collecting an unverified but extensive family history of cancer and displaying it as a pedigree, in an entirely automated process.

The prevalence of autistic spectrum disorders in adolescents with a history of specific language impairment (SLI)

Traditionally, autism and specific language impairment (SLI) have been regarded as distinct disorders but, more recently, evidence has been put forward for a closer link between them: a common set of language problems, in particular receptive language difficulties and the existence of intermediate cases including pragmatic language impairment. The present study aimed to examine the prevalence of autism spectrum disorders in a large sample of adolescents with a history of SLI. The presence of autism spectrum disorders was examined in seventy-six 14-year-olds with a confirmed history of SLI. A variety of instruments were employed, including the Autism Diagnostic Interview-Revised (ADI-R), the Autism Diagnostic Observation Schedule (ADOS) and the Family History Interview (FHI). The prevalence of autism spectrum disorders in young people with SLI was found to be 3.9%, about 10 times what would be expected from the general population. In addition, a much larger number of young people with a history of SLI showed only some autism spectrum symptoms or showed them in a mild form. Young people with SLI have an increased risk of autism. The magnitude of this risk is considerable. In addition, a larger proportion (a quarter of individuals) present with a number of behaviours consistent with autism spectrum disorders.

Risk factors and early signs of Alzheimer's disease in a family study sample

Several predictors of Alzheimer's disease (AD) have been identified. However, the relevance and independent contribution of risk factors and of possible early signs such as mild cognitive impairment and subjective memory impairment on the development of AD has not been investigated prospectively in a cohort of non-demented elderly including first-degree relatives of AD subjects. The development of AD was investigated in 757 non-demented elderly. Initial diagnoses were made from personal interviews. Information on 633 subjects after 4.7 +/- 1.2 years (mean +/- SD) was obtained either from personal or family history interviews. Using forward logistic regression analysis, predictors were identified by comparing their presence in 38 subjects who developed AD and 577 subjects who remained non-demented. The most important predictors of later Alzheimer's disease were increased age (Odds ratio OR = 1.086/additional year, p < 0.001), initial subjective memory complaints (OR = 2.68, p = 0.019), initial mild cognitive impairment (OR = 2.51, p = 0.032) and female gender (OR = 2.84, p = 0.069). Exploratory analysis revealed that previous depression after the age of 60 years (OR = 2.37, p = 0.033) and the presence of the apolipoprotein E4 allele (OR = 2.49, p = 0.043) individually predicted new AD during follow-up. A positive family history of AD (i. e. being a first degree relative of a subject suffering from AD) did not significantly influence the development of AD (p > 0.2). Increased age, the presence of mild cognitive impairment, subjective memory impairment and gender are the most relevant independent predictors of later Alzheimer's disease that may be used in combination for clinical prediction of AD.

Stress reactivity and family relationships in the development and treatment of endometriosis

To examine stress physiology and facts of family functioning associated with development and course of endometriosis symptoms. Clinical case data and literature review. Private practice in hospital-affiliated medical office. One woman with endometriosis, her parents, and a nonsymptomatic volunteer. Measures of physiologic and neural reactivity with biofeedback and neurofeedback equipment during family history interview and while sitting quietly. Electroencephalography (EEG), digital skin temperature (DST), electrodermal response (EDR), and electromyography (EMG); facts of family history; contact with family. Endometriosis symptoms were associated with DST, EDR, EMG, and EEG measures indicating prolonged stress reactions for the symptomatic woman and her parents. Facts of family history and relationships for three generations set the stage for stress reactions. Striking differences are evident in the physiology, family history, and contact with family of the nonsymptomatic woman. Differences warrant further study, a larger sample, and additional measures using hormone assay to establish connections between stress reactions in the family, endometriosis symptoms, and response to treatment. Further research will document changes in physiology and in symptoms that accompany interruption of stress reactions with self-regulation training and family systems psychotherapy.

Joubert syndrome is not a cause of classical autism

A previous report noted a 27% prevalence of autism in Joubert syndrome (JS), raising the question of overlapping etiologies. Family studies have shown that autism is characterized by family loading for a number of specific behavioral and psychiatric disorders and that the sib recurrence risk is around 4%. The purpose of this study is to determine whether children with Joubert and their families show behavioral or genetic characteristics similar to autism. Thirty-one volunteer Joubert families were identified. Parents completed a semi-structured family history interview and the Autism Behavioral Checklist. Rates of family loading for neuropsychiatric disorders in the JS families were compared to autism family history data and Down syndrome (DS) controls. The JS families had significantly lower rates of autism, alcoholism, cognitive, and language disorders than the autism families. Their rate of depression was lower, but not significantly different from that found in autism families. None of the JS children met the clinical cut-off for autism based on parental symptom report and the sib recurrence risk was 32% for the JS families compared to 4% for the autism and 0% for DS families. These data indicate that JS is a genetically distinct disorder from autism. Different genes with different inheritance patterns that affect neurodevelopment of the cerebellum could explain the clinical similarities previously reported in JS and autism.

Cancer Risk AssessmentQuality and Impact of the Family History Interview

Background: Identification of individuals at high risk for colon and breast cancer requires an adequate family history assessment and can influence cancer screening and genetic testing decisions. Little data exist that evaluate the completeness of the family history interview in primary care. Methods: Retrospective chart review of 995 new patient visits to 28 primary care physicians evaluating the completeness of the family cancer history for colon or breast cancer. Family history information was evaluated for inclusion of age at diagnosis, degree of kinship, and specification of disease of interest. Results: Family history information on cancer diagnoses was collected on 679 (68%) of the patients. Specific information regarding the individual affected and the cancer diagnosis was present in 414 (61%) of the records. Affected first-degree relatives were more likely to have their age of cancer diagnosis recorded than second-degree relatives (39%, 95% confidence interval [CI]=34%–44% vs 16%, 95% CI=12%–20%). Age at diagnosis of cancer in first-degree relatives was documented in 51% of colon cancers, 38% of breast cancers, and 27% of ovarian cancers. Only 17% of individuals who meet criteria for early-onset breast cancer genetic testing were referred for genetic services. Conclusions: Adequate cancer risk assessment using family history information requires age at cancer diagnosis and specification of a cancer diagnosis. Age at diagnosis was frequently missing from family history assessments, which could have a potential impact on identification of high-risk individuals. When family history information does identify high-risk individuals, only the minority are referred for genetic services. Identification of individuals at high risk for colon and breast cancer requires an adequate family history assessment and can influence cancer screening and genetic testing decisions. Little data exist that evaluate the completeness of the family history interview in primary care. Retrospective chart review of 995 new patient visits to 28 primary care physicians evaluating the completeness of the family cancer history for colon or breast cancer. Family history information was evaluated for inclusion of age at diagnosis, degree of kinship, and specification of disease of interest. Family history information on cancer diagnoses was collected on 679 (68%) of the patients. Specific information regarding the individual affected and the cancer diagnosis was present in 414 (61%) of the records. Affected first-degree relatives were more likely to have their age of cancer diagnosis recorded than second-degree relatives (39%, 95% confidence interval [CI]=34%–44% vs 16%, 95% CI=12%–20%). Age at diagnosis of cancer in first-degree relatives was documented in 51% of colon cancers, 38% of breast cancers, and 27% of ovarian cancers. Only 17% of individuals who meet criteria for early-onset breast cancer genetic testing were referred for genetic services. Adequate cancer risk assessment using family history information requires age at cancer diagnosis and specification of a cancer diagnosis. Age at diagnosis was frequently missing from family history assessments, which could have a potential impact on identification of high-risk individuals. When family history information does identify high-risk individuals, only the minority are referred for genetic services.

Cancer Risk Assessment: Quality and Impact of the Family History Interview

Identification of individuals at high risk for colon and breast cancer requires an adequate family history assessment and can influence cancer screening and genetic testing decisions. Little data exist that evaluate the completeness of the family history interview in primary care. Retrospective chart review of 995 new patient visits to 28 primary care physicians evaluating the completeness of the family cancer history for colon or breast cancer. Family history information was evaluated for inclusion of age at diagnosis, degree of kinship, and specification of disease of interest. Family history information on cancer diagnoses was collected on 679 (68%) of the patients. Specific information regarding the individual affected and the cancer diagnosis was present in 414 (61%) of the records. Affected first-degree relatives were more likely to have their age of cancer diagnosis recorded than second-degree relatives (39%, 95% confidence interval [CI]=34%-44% vs 16%, 95% CI=12%-20%). Age at diagnosis of cancer in first-degree relatives was documented in 51% of colon cancers, 38% of breast cancers, and 27% of ovarian cancers. Only 17% of individuals who meet criteria for early-onset breast cancer genetic testing were referred for genetic services. Adequate cancer risk assessment using family history information requires age at cancer diagnosis and specification of a cancer diagnosis. Age at diagnosis was frequently missing from family history assessments, which could have a potential impact on identification of high-risk individuals. When family history information does identify high-risk individuals, only the minority are referred for genetic services.

Hereditary ovarian cancer in Poland

Background. Uterine papillary serous carcinoma (UPSC) shares common pathologic, genetic, and clinical features with other serous cancers of müllerian origin. The most common histologic type of ovarian tumor associated with BRCA mutations is papillary serous. Because of these histologic similarities, we postulated that, in some cases, UPSC may be a manifestation of a field defect in BRCA1 carriers, which also includes ovarian carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma.Methods. Fifty-six living patients with UPSC were contacted through their treating physicians and agreed to a family history interview and to provide a blood specimen for BRCA testing. The protein truncation test was used to detect mutations in exons 10 and 11 of BRCA1 and in exon 11 of BRCA2. The presence of four common mutations was assessed by PCR-based specific assays.Results. A high proportion of patients had a past history of breast cancer (11%) or a first-degree relative with breast cancer (29%). Four patients were from families with site-specific hereditary breast cancer. However, there was no clear example of the hereditary breast–ovarian cancer syndrome, and none of the 56 patients was found to carry a BRCA1 or BRCA2 mutation.Conclusions. BRCA mutations do not appear to predispose to UPSC and this type of cancer does not appear to be a manifestation of the classical hereditary breast–ovarian cancer syndrome. The observed association between UPSC and breast cancer may be due to the presence of mutations in other cancer predisposing genes.