Comparison of compliance for colorectal cancer screening and surveillance by colonoscopy based on risk

PurposeTo compare colonoscopy screening/surveillance rates by level of risk for colorectal cancer based on age, personal history of adenomatous polyps or colorectal cancer, or family history of colorectal cancer.MethodsParticipants were aged 30–90 years, were seen within 5 years at Intermountain Healthcare, and had family history in the Utah Population Database. Colonoscopy rates were measured for those with/without risk factors.ResultsAmong those aged 60–69 years, 48.4% had colonoscopy in the last 10 years, with rates declining after age 70 years. Percentages of those having had a colonoscopy in the last 10 years generally increased by risk level from 38.5% in those with a familial relative risk <1.0 to 47.6% in those with a familial relative risk >3.0. Compared with those with no family history, the odds ratio for being screened according to guidelines was higher for those with one first-degree relative diagnosed with colorectal cancer ≥ 60 years or two affected second-degree relatives (1.54, 95% confidence interval: 1.46–1.61) than those with one affected first-degree relative diagnosed <60 years or ≥2 affected first-degree relatives (1.25, 95% confidence interval: 1.14–1.37).ConclusionsCompliance with colonoscopy guidelines was higher for those with familial risk but did not correspond with the degree of risk.     

Familial occurrence of inflammatory bowel disease

BACKGROUND AND METHODS. We assessed the familial occurrence of inflammatory bowel disease in Copenhagen County, where there has been a long-term interest in the epidemiology of such disorders. In 1987 we interviewed 662 patients in whom inflammatory bowel disease had been diagnosed before 1979, asking whether their first- and second-degree relatives had this disorder. Ninety-six percent of the patients (504 with ulcerative colitis and 133 with Crohn's disease) provided adequate information. RESULTS. As compared with the general population, the first-degree relatives of the 637 patients with ulcerative colitis or Crohn's disease had a 10-fold increase in the risk of having the same disease as the patients, after standardization for age and sex. The risk of having the other of the two diseases was also increased, but less so, and the increase in the risk of having Crohn's disease was not significant in the relatives of patients with ulcerative colitis. The risk of ulcerative colitis in first-degree relatives of patients with ulcerative colitis appeared to be virtually independent of the generation to which the first-degree relative belonged and of the sex of the patient and the relative. The risk of ulcerative colitis in first-degree relatives tended to be higher if the disease had been diagnosed in the patient before the age of 50, but the risk seemed to be independent of the current age of the relatives. The prevalence of the same disease as that of the patient (either ulcerative colitis or Crohn's disease) among second-degree relatives was increased; the prevalence of the other disease was not increased. CONCLUSIONS. The 10-fold increase in the familial risk of ulcerative colitis and Crohn's disease strongly suggests that these disorders have a genetic cause.     

A family study of obsessive-compulsive disorder with pediatric probands.

Obsessive-compulsive disorder (OCD) is a heterogeneous disorder of unknown etiology. We examined the lifetime history of obsessions, compulsions, and OCD in the first- and second-degree relatives of 35 pediatric probands with OCD and 17 controls with no psychiatric diagnosis. All available first-degree relatives were directly interviewed blind to proband status with two semi-structured interviews. Parents were also interviewed to systematically assess the family psychiatric history of first- and second-degree relatives. Best-estimate lifetime diagnoses were made using all available sources of information. Data were analyzed with logistic regression by the generalized estimating equation method and with robust Cox regression models. The lifetime prevalence of definite OCD was significantly higher in case than control first-degree relatives (22.5% vs. 2.6%, P < 0.05). Compared to controls, case first-degree relatives also had significantly higher lifetime rates of obsessions and compulsions (both P < 0.05). There was no significant difference between case and control second-degree relatives in lifetime rates of OCD. First-degree relatives of case probands with ordering compulsions had a significantly higher lifetime rate of definite and subthreshold OCD than relatives of case probands without ordering compulsions (45.4% vs. 18.8%, P < 0.05). The lifetime prevalence of definite OCD was significantly higher in case first-degree relatives with a history of tics than in case first-degree relatives without a tic history (57.1% vs. 20.9%, P < 0.01). The results provide further evidence that early-onset OCD is highly familial and suggest that two clinical variables are associated with its familial aggregation.     

Impact of patient age on family cancer history.

PURPOSE: Younger individuals with relatives diagnosed with cancer are at greater risk for developing certain cancer when compared with older individuals with affected relatives. The purpose of this study was to calculate the age-specific proportion of individuals reporting positive family histories for colon, breast, and prostate cancer. METHODS: Family cancer history information was reviewed on 32,374 adults interviewed for the 2000 National Health Interview Survey. Family histories were categorized as high risk, with a relative diagnosed before 50 years of age or with multiple affected relatives, or moderate risk, with a single relative diagnosed at age 50 years or older. RESULTS: For individuals with a family history of colorectal cancer, the odds of having a high-risk pedigree decreased by 1% (95% confidence interval 0%-2%) for every year of age increase. For women reporting a family breast cancer history, the odds of reporting a pedigree with high-risk features decreased by 3% (95% confidence interval 2%-4%) for each year of age increase. Age was not associated with reporting a high-risk pedigree for prostate cancer. CONCLUSION: For colorectal and breast cancers, younger individuals reporting a family history of these cancers were more likely to report a pedigree with high-risk features than older individuals.     

Malignancy of recurrent, early-onset major depression: a family study.

Coordinated efforts to identify susceptibility genes for unipolar major depressive disorder (MDD) and related disorders are now underway. These studies have focused on recurrent, early-onset MDD (RE-MDD), the most heritable form of this disorder. The goal of this study was to characterize the burden of MDD and other mood disorders, comorbid mental disorders, and excess mortality in RE-MDD families. A total of 81 families were identified through probands over the age of 18, who met criteria for recurrent (> or = 2 episodes), early-onset (< or = 25 years), nonpsychotic, unipolar MDD (RE-MDD), and included 407 first-degree relatives and 835 extended relatives. Psychiatric diagnoses for probands and their family members who provided blood samples were formulated from structured personal interviews, structured family history assessments, and available medical records. The remaining family members who participated and those who were deceased were evaluated through the family history method augmented by available medical records. Best estimate diagnoses were made during a consensus conference according to established diagnostic criteria. Approximately half of the first-degree relatives and a quarter of extended relatives of RE-MDD probands suffered from at least one mood disorder, typically MDD. As commonly observed for other oligogenic, multifactorial disorders, the severity of MDD reflected by age at onset and number of episodes attenuated with increasing familial/genetic distance from the proband. A substantial fraction of RE-MDD probands and their first-degree relatives met diagnostic criteria for additional psychiatric disorders that include prominent disturbances of mood. The deceased relatives of RE-MDD probands died at a median age that was 8 years earlier than for the local population; over 40% died before reaching age 65. These differences in mortality statistics resulted from a shift toward younger ages at death across the lifespan, including a fivefold increase in the proportion of individuals who died in the first year of life. Several-fold increases in the proportion of deaths by suicide, homicide, and liver disease were observed among the relatives of RE-MDD probands. However, the rank order of the three most common causes of death-heart disease, cancer, and stroke-remained unchanged and differences in the proportions of deaths from the remaining causes were small. RE-MDD is a strongly familial condition with a high rate of psychiatric comorbidity, whose malignant effects have a significant negative impact on the health and longevity of patients and their family members.     

How does a simple enquiry compare to a detailed family history questionnaire to identify coronary heart disease or diabetic familial risk?

PurposeTo examine whether a simple enquiry can provide similar family history information compared with a detailed questionnaire for coronary heart disease or diabetes.MethodsData from two randomized controlled trials were extracted that assess the clinical value of using family history information for either coronary heart disease (ISRCTNI17943542) or diabetes risk assessment (NTR1938) in a community-based population. Outcome measures were percentage agreement, sensitivity, and specificity of self-reported family history for coronary heart disease and diabetes by means of a simple enquiry, when compared with a detailed questionnaire.ResultsAgreement between both family history tools was 76.8% for first-degree relatives with coronary heart disease, and 89.2% and 87.6% for first- and second-degree relatives with diabetes, respectively. The sensitivity was 44.2% for first-degree relatives with coronary heart disease, 81.9% for first-degree relatives with diabetes, and 35.4% for second-degree relatives with diabetes. Specificity was 89.3%, 97.0%, and 94.5%, respectively.ConclusionCompared with a detailed questionnaire, the simple enquiry correctly identified the majority of individuals classified as having no significant family history but missed a significant proportion of individuals with positive family history. Incorrect classification of family history, in particular the high false-negative rate, has implications on the utility of a simple enquiry in identifying familial risk in clinical practice.     

Comorbid major depression and panic disorder: significance of temporal sequencing to familial transmission

BACKGROUND: Panic disorder (PD) and major depression frequently coexist but the nature of the relationship is controversial. Our aim was to determine if the risk for depression in a proband is influenced by the temporal sequence of comorbid PD and major depression in an affected family member. METHODS: Of participants in a larger study of individuals who had a family, but no personal history of PD, 31 had a first-degree relative with comorbid PD and major depressive disorder (MDD). In 16, the onset of MDD preceded PD (HR-MDPD), and in 15, PD was established before the first depressive episode (HR-PDMD). Thirty-seven low-risk controls (LRC) described no first-degree relatives with psychiatric illness. Participants were assessed using the SADS-LA and provided family history data on first-degree relatives. RESULTS: High-risk subjects whose first-degree relative had temporally primary depression had a 50% chance of having had a major depressive episode. Those with a first-degree relative with primary panic and secondary depression were at no greater risk of having had a depression than were normal controls (6.7% and 5.4%, respectively). LIMITATIONS: The use of the family history method has the intrinsic weakness of relying solely on proband knowledge. CONCLUSION: The temporal relationship between comorbid panic and depression may play an important role in determining the familial risk for depression in family members.     

Relation of familial patterns of coronary heart disease,stroke, and diabetes to subclinical atherosclerosis: the multi-ethnic study of atherosclerosis

PurposeTo investigate the possibility that family history beyond early-onset coronary heart disease might contribute to coronary heart disease susceptibility, we studied associations between additional family history and the coronary artery calcium score.MethodsAssociations between coronary artery calcium score and self-reports of coronary heart disease, stroke, and diabetes in first-degree relatives of 5264 nondiabetic subjects were assessed using logistic and linear regression adjusting for risk factors; adjusted mean coronary artery calcium score estimates were determined by pooling results.ResultsFamily history of coronary heart disease alone and in combination with diabetes and/or stroke was significantly associated with a positive coronary artery calcium score compared with no family history with odds ratios ranging from 1.7 (95% CI: 1.3–2.3) to 1.9 (95% CI: 1.6–2.3) and adjusted mean coronary artery calcium score estimates ranging from 137 (95% CI: 101–173) to 184 (95% CI: 143–226). Associations between family history of coronary heart disease and coronary artery calcium score were significant regardless of age at onset, sex, lineage, or number of relatives with coronary heart disease. The association between family history of diabetes only and coronary artery calcium score was also significant (OR, 1.3; 95% CI: 1.1–1.7) with an adjusted mean coronary artery calcium score estimate of 122 (95% CI: 93–151). Generally, family history of stroke had nonsignificant associations with coronary artery calcium score.ConclusionsNumerous family history variables in addition to early-onset coronary heart disease are associated with subclinical atherosclerosis. Our results have implications for improving coronary heart disease risk assessment.     

Unipolar depression in the aged: determinants of familial aggregation.

Late-onset depression (greater than or equal to 60 years) is believed to be less associated with a risk of depression in first-degree relatives than early-onset depression. However, family studies in elderly probands fitting the current methodological standards of family studies are not available. The reported family study in geriatric inpatients with unipolar major depression (n = 92) supported the proposed relationship between age at onset and the proposed familial loading. A comparison to families of age-matched controls (n = 33) revealed that relatives of probands with late-onset depression are still at an increased risk of depression. However, late-onset depression was not more common in families of probands with late-onset depression than in families of probands with early-onset depression. Besides the age at onset, the recurrence of depressive episodes defined distinct patterns of familial aggregation.     

Population-based screening for hereditary breast cancer in a region of North-Central Italy

Assessment of family history is an important element in the identification of individuals and families likely to be at risk of hereditary cancers. It is based on the recognition of important features in the natural history of cancer syndromes. These include the occurrence of the same type of cancer in two or more close relatives, bilateral cancer in paired organs, multiple primaries in the same individual, early age at onset, a specific constellation of cancers or other physical findings associated with a known syndrome, and a mendelian pattern of inheritance. We set up a population-based screening program to identify women at increased risk of breast or ovarian cancer in a region of North-Central Italy. As a preliminary screening, 159 women with a family history of breast and ovarian cancer were recruited at the Cancer Prevention Unit of Pierantoni Hospital in Forli. Information on the number of affected individuals and the age at onset of breast or ovarian cancer in each woman's family was recorded. Thirty-nine women reported two or more first- or second-degree relatives with breast cancer under the age of 50 (25%) and 95 a single first- or second-degree relative with breast cancer under the age of 50 (60%) with or without other late onset breast cancers in the family. The remaining 25 women reported first- and second-degree relatives with breast cancer over the age of 50 (15%). There were five families with a history of ovarian cancer (3%), one of which comprised 3 affected members. Twenty-three families showed multiple cancers associated with breast cancer cases. Associated prostate and colorectal cancers were found in 5 and 4 families with a history of breast cancer, respectively. On the basis of these preliminary data, we aimed to extend the population-based screening to the whole of the Emilia-Romagna population, involving the Cancer Prevention Units of neighboring towns and adopting homogeneous family history evaluation and risk assessment criteria.     

The familial prevalence in second-degree relatives of patients with anxiety neurosis (panic disorder)

A family history study of second-degree relatives of 19 patients with anxiety neurosis (panic disorder) and 19 controls showed a morbidity risk of 9.5% among the former compared with 1.4% among the latter. These risks were approximately half those found among first-degree relatives. Female relatives were at higher risk for anxiety neurosis. The risk for other psychiatric illnesses did not differ between the relatives of anxiety neurosis and controls.     

Characteristics of familial aggregation in early-onset Alzheimer's disease: Evidence of subgroups

Characteristics of familial aggregation of Alzheimer's Disease were studied in 92 families ascertained through a clinically diagnosed proband with an onset below age 60 years. In each family data were systematically collected on the sibships of the proband, of his father, and of his mother. A total of 926 relatives were included and 81% of the living relatives (i.e., 251 individuals) were directly examined. The estimated cumulative risk among first degree relatives was equal to 35% by age 89 years (95% confidence interval 22 to 47%). This result does not support the hypothesis that an autosomal dominant gene, fully penetrant by age 90 years, is segregating within all these pedigrees. Despite the fact that all probands were selected for an onset before age 60 years it was shown that two types of families could be delineated with respect to age at onset among affected relatives: all secondary cases with an onset below age 60 years were contributed by a particular group of families (type 1 families), whereas all secondary cases with an onset after age 60 years were contributed by another group of families (type 2 families). Although genetic interpretation of these findings is not straightforward, they support the hypothesis of etiologic heterogeneity in the determinism of early-onset Alzheimer's disease. © 1995 Wiley-Liss, Inc.     

Family history of insomnia in a population-based sample

STUDY OBJECTIVES: To examine the rates of family history of insomnia in a population-based sample composed of self-defined good sleepers and individuals with insomnia and compare individuals with and without family history of insomnia on several characteristics presumably associated with insomnia. DESIGN: Cross-sectional comparisons of self-defined good sleepers and individuals with insomnia selected from a larger epidemiologic study using a randomly selected sample of 2001 adults of the province of Quebec in Canada. PARTICIPANTS: Nine hundred fifty-three adults (60.3% women; mean age = 43.9 years) completed several postal questionnaires, including a survey of past and current history of insomnia/sleep disorders for self and first-degree relatives. Participants were classified as good sleepers, individuals with insomnia symptoms, or individuals with an insomnia syndrome. INTERVENTIONS: N/A. RESULTS: Of the total sample, 34.9% reported at least 1 first-degree relative with past or current insomnia. The mother was the most frequently afflicted first-degree relative with insomnia (19.7%). Family history rates of insomnia were not significantly different when individuals with current insomnia symptoms or syndrome were compared with self-defined good sleepers. However, significant group differences emerged when good sleepers were subdivided according to the presence or absence of past personal history of insomnia. Individuals with past or current insomnia were significantly more likely to report a family history of insomnia than were good sleepers who had never experienced insomnia in the past (39.1% vs 29.0%). Participants with a family history of insomnia endorsed higher scores on measures of insomnia severity, anxiety symptomatology, and arousal predisposition. CONCLUSIONS: These findings provide additional evidence about the potential role of both family and personal history of insomnia as predisposing factors to insomnia. Longitudinal family studies are needed to further examine the relative contribution of genetic and environmental factors in the genesis and heritability of insomnia.     

Association Between Familial Autoimmune Diseases and Recurrent Spontaneous Abortions

PROBLEM: To examine the aggregation of autoimmune diseases in the families of women experiencing recurrent spontaneous abortions. METHOD: The 95 participants in this case-control study were recruited from Magee Womens Hospital, Pittsburgh, Pennsylvania from June 1988 to May 1991. The women having recurrent spontaneous abortions (N = 45) reported at least three early fetal losses, and the controls (N = 50) reported a minimum of three pregnancies with at least two live births and no more than one induced or involuntary pregnancy loss. Data from the participants and from their first-degree and second-degree relatives were obtained by questionnaire and verified by a repeated interview, if necessary. RESULTS: The prevalence of arthritis, thyroid disease, and diabetes mellitus was increased among the relatives of women having recurrent spontaneous abortions compared to normally fertile couples. Several autoimmune diseases occurred concurrently in family members of patients, but not in the family members of normally fertile couples. CONCLUSIONS: Autoimmune diseases occur more frequently in the families of women who have experienced recurrent spontaneous abortions. Both types of diseases involve genes in the class II region of the major histocompatibility complex.     

Genetic testing impacts the utility of prospective familial screening in hypertrophic cardiomyopathy through identification of a nonfamilial subgroup

PurposeHypertrophic cardiomyopathy (HCM) is considered a hereditary autosomal dominant condition, but genetic testing is positive in only half of patients. In patients with negative genetic tests, the inheritance pattern and utility of family screening are unclear.MethodsSubjects with HCM were prospectively enrolled in a registry. A survey at a median follow-up of 4 years determined the yield of family screening.ResultsThe outcome of cardiac screening on 267 family members was reported by 120 survey respondents. Subjects with positive genetic test or family history (n=74, 62%) reported an HCM diagnosis in 34 of 203 first-degree relatives who were screened (17%). Affected family members were diagnosed at a mean age of 30–39 years, and 22 of 34 experienced HCM-related adverse events (65%). Gene test–negative subjects with no prior family history of HCM (n=46, 38%) reported an HCM diagnosis in only 2 of 64 first-degree relatives who were screened (3%, p<0.001). These two individuals were diagnosed at age >40 years without HCM-related adverse events.ConclusionHypertrophic cardiomyopathy is a heterogeneous disorder, only half of which tracks with a Mendelian inheritance pattern. Negative genetic testing and family history indicates a more complex genetic basis corresponding to low risk for family members.     

Risk factors for detecting germline BRCA1 and BRCA2 founder mutations in Ashkenazi Jewish women with breast or ovarian cancer

We ascertained 184 Ashkenazi Jewish women with breast/ovarian cancer (171 breast and 13 ovarian cancers, two of the former also had ovarian cancer) in a self-referral study. They were tested for germline founder mutations in BRCA1 (185delAG, 5382insC, 188del11) and BRCA2 (6174delT). Personal/family histories were correlated with mutation status. Logistic regression was used to develop a model to predict those breast cancer cases likely to be germline BRCA1/BRCA2 mutation carriers in this population. The most important factors were age at diagnosis, personal/family history of ovarian cancer, or breast cancer diagnosed before 60 years in a first degree relative. A total of 15.8% of breast cancer cases, one of 13 ovarian cancer cases (7.7%), and both cases with ovarian and breast cancer carried one of the founder mutations. Age at diagnosis in carriers (44.6 years) was significantly lower than in non-carriers (52.1 years) (p<0.001), and was slightly lower in BRCA1 than BRCA2 carriers. Thirty three percent of carriers had no family history of breast or ovarian cancer in first or second degree relatives. Conversely, 12% of non-mutation carriers had strong family histories, with both a first and a second degree relative diagnosed with breast or ovarian cancer. The predicted values from the logistic model can be used to define criteria for identifying Ashkenazi Jewish women with breast cancer who are at high risk of carrying BRCA1 and BRCA2 mutations. The following criteria would identify those at approximately 10% risk: (1) breast cancer <50 years, (2) breast cancer <60 years with a first degree relative with breast cancer <60 years, or (3) breast cancer <70 years and a first or second degree relative with ovarian cancer.     

Increased sister chromatid exchange frequency in young women with breast cancer and in their first-degree relatives

The well-known increased risk of breast cancer (BC) in first-degree relatives of patients with BC has been related to shared genetic factors including defective DNA repair, with loss of genomic integrity. On the other hand, it can be hypothesized that early-onset breast cancer is also associated with overburden of heritable factors leading to increased DNA injury. In this respect, we analyzed sister chromatid exchange frequency (SCE) in 20 women with breast cancer (all < or =40 years old), in their first-degree female relatives, and in 20 age-matched healthy females without a personal or family history of cancer. SCE was significantly increased (P < 0.05) in patients (7.17 +/- 1.81 per metaphase) and in their first-degree relatives (6.44 +/- 0.98), compared with controls (5.85 +/- 0.72). There was no difference in SCE frequency between patients and their first-degree relatives. We suggest that the increased SCE in patients reflects a genomic instability that may be operative in carcinogenesis. Further, genomic instability is shared also by first-degree relatives, although none of them had a history of breast cancer at the time of the study.     

Familial papillary carcinoma of the thyroid

Of 226 consecutive papillary carcinoma patients, 14 indicated that at least one other relative was similarly affected. Pathology confirmation was obtained in 8 of the 14 families. Of the eight families with documented familial papillary carcinoma, one had five members, another had four members, and yet another had three members affected. The remaining families had two members affected. In those families with two or more persons with confirmed papillary carcinomas of the thyroid, 20 first- and second-degree relatives were examined. Of those, one had a previously unidentified papillary carcinoma and 6 had a benign thyroid disease (4 primary hypothyroidism and 2 simple goiters). High-resolution chromosome studies of four patients from four different families were normal, and there was no increase in chromosome breakage in a fifth patient from yet another family. Autosomal dominant inheritance is possible. Although there was no family history of lipomas, osteomas, or intestinal polyposis to suggest Gardner syndrome, four parents of our familial papillary carcinoma patients had colon cancer. In addition, three other relatives died of unidentified intra-abdominal cancer. The apparently high frequency of colon cancer and other abdominal cancer in relatives was an additional concern. Based on our observations, three clinical recommendations can be made: obtain a family history of all patients with papillary carcinoma of the thyroid, since between 3.5 to 6.2% will have another affected relative; when two or more persons in a family have papillary carcinoma of the thyroid, all first- and second-degree relatives should have a neck palpation by an experienced examiner; and families with two or more persons with papillary carcinoma should be observed for possible colon cancer.     

Uptake of genetic counselling and predictive DNA testing in hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy is a common autosomal dominant disease, associated with heart failure and arrhythmias predisposing to sudden cardiac death. After the detection of the causal mutation in the proband predictive DNA testing of relatives is possible (cascade screening). Prevention of sudden cardiac death in patients with a high risk by means of an implantable cardioverter defibrillator is effective. In 97 hypertrophic cardiomyopathy families with a sarcomere gene mutation we retrospectively determined uptake of genetic counselling and predictive DNA testing in relatives within 1 year after the detection of the causal mutation in the proband. Uptake of genetic counselling was 39% and did not differ significantly by proband's or relative's gender, nor by young age of the relative (< 18 years) or a family history positive for sudden cardiac death. In second-degree relatives, eligible for predictive DNA testing when the first-degree relative had died, uptake was 27.5% (P = 0.047). Uptake of predictive genetic testing was 39%; conditional uptake of predictive genetic testing was 99%. Uptake of genetic counselling in hypertrophic cardiomyopathy is comparable to uptake in oncogenetics. Conditional uptake of predictive DNA testing, however, is much higher. Because sudden cardiac death can be prevented uptake of genetic counselling in hypertrophic cardiomyopathy should be as high as possible. To achieve this research into the determinants of uptake is needed.     

Possible consequences of applying guidelines to healthy women with a family history of breast cancer

Possible effects of consistently applying published guidelines on healthy women with breast cancer in their family history were analysed. We investigated 1060 unrelated breast cancer patients and calculated the numbers of first-degree relatives that would be referred to a familial cancer clinic if the guidelines were consistently applied. A first-degree relative was considered a candidate for referral if she was female, without breast cancer at the moment of the interview, alive and over the age of 24. The criteria for referral were based on one Dutch and two British guidelines. According to the Dutch guideline, for one affected woman with breast cancer, 0.25 (95% CI 0.22-0.28) healthy first-degree female relatives should be offered a consultation at a familial cancer clinic (FCC). Application of the British guidelines would lead to a similar number of referrals. Of all healthy first-degree female relatives, who should be referred to an FCC, 34-37% had an index case among their family who was already known at a genetic department. If current guidelines are consistently applied, a sharp increase in referrals to FCCs may be expected. These guidelines, however, are arbitrary and only limited data are available on the efficacy of this surveillance for high-risk healthy women.