Degree Female Relatives Research Articles

Pathogenic germline variants in patients with breast cancer: conversations across generations, practices and patients' attitude.

Background: Breast cancer susceptibility genes such as BRCA1, BRCA2, PALB2, CHEK2 and many others are increasingly recognized among our patient population. In addition to their impact on treatment decisions of tested patients themselves, identifying at-risk family members offer opportunities for cancer preventive measures. Methods: This is an observational cross-sectional study of adult breast cancer patients with positive breast-cancer-susceptibility germline variants who received treatment at our institution. Patients with variants of uncertain significance (VUS), or who refused to give consent, were excluded. The data was collected from an eligible sample of breast cancer patients using a structured questionnaire developed by the study team and tested for validity and reliability, as well as a clinical chart review form. Patients were invited to participate in the study during their scheduled oncology clinics visit. Results: 169 patients were enrolled, including 42 (24.9%) with pathogenic/likely pathogenic (P/LP) BRCA1 variants, 84 (49.7%) with BRCA2 and 43 (25.4%) with non-BRCA variants. All patients were female and the mean age was 45 ± 9.9years. Among 140 eligible patients, 104 (74.3%) underwent prophylactic mastectomy, while 79 (59.0%) of 134 eligible patients had prophylactic bilateral salpingo-oophorectomy (BSO). Results were communicated with family members by majority (n = 160, 94.7%), including 642 first degree female relatives, and 286 (44.5%) of them have taken no action. Fear of positive test results, cost of testing, unwillingness to undergo preventive measures, and social stigma were cited as barriers to genetic testing in 54%, 50%, 34% and 15%, respectively. Conclusion: Risk-reducing interventions including mastectomy and BSO were carried by majority of patients with P/LP variants. However, though the rate of communication of genetic testing results with family members was high, proper preventive measures were relatively low. Cost and fear of cancer diagnosis, were the leading causes that prevented cascade testing in our cohort.

Abstract P2-09-17: Family communication and attitude of patients with breast cancer toward positive pathogenic BRCA1 or BRCA2 mutations. A regional perspective

Abstract Background: Since the discovery of breast cancer susceptibility genes BRCA1 & BRCA2 and the availability of genetic testing, a considerable amount of research has been conducted to evaluate rates of genetic test acceptance and to understand the psychological and behavioural impact of genetic test results on both patients and their family members. This study aims to explore the experience of women who tested positive for a cancer-predisposing gene, and to identify risk reduction interventions patients had or planning to have and study if patients communicated genetic test results with at-risk family members and intervention made by the family members. Methods: A questionnaire was designed to assess socio-demographic factors, personal and family history of cancer, genetic test results and family notification of testing, and subsequent testing in relatives. Participants were invited to participate in the study during their visit to their oncologist clinic, in addition to patients that were invited via Teleclinic using different meeting platforms. Results: Ninety-nine patients with the pathogenic BRCA 1 or BRCA 2 mutations, who were diagnosed with breast cancer between the years 2005 and 2020, were enrolled in the study. The Mean age of participants was 45 years (range from 27 to 77 years). The patients reported different emotional reactions to the positive results of cancer genetic testing; 39 (39%) experienced feelings of anxiety, 69 (69%) were afraid about the risk of their children carrying the disease. While 24 (24%) of participants reported they felt comforted because they can take preventive measures for them and their family members and only 5 (5%) were worried about health insurance coverage. Thirteen (13%) of the patients reported that their social status had been affected by the genetic testing results. The majority (n=74, 74%) believed in the importance of communicating the results with their families. Ninety-eight (98%) patients have informed their family members of the results and only 1 (1%) did not inform anyone of the results. In total, 922 relatives were informed of the results of genetic testing and only 31 (3.3%) underwent genetic testing in response. A total of 379 first degree female relatives (mother, sister, and daughter) were informed about the genetic testing results and only 24 (6.6%) underwent genetic testing for BRCA mutations and only 8 (2%) patients underwent a prophylactic mastectomy. The reasons that prevented the informed family members from undergoing the genetic testing were diverse. As reported by the patients participating in the study, the cost of testing was the most reported reason in 54% of the time. And 52 patients (52%) considered fear from having a positive test as the main reason. The social stigma of carrying a cancer gene was also a factor in 16% of cases. Conclusion: Despite the high rate of communicating BRCA results with family members, there is lack of awareness of the proper preventive measures to be followed to decrease the risk of breast cancer. Citation Format: Rawan Mustafa, Khawla Ammar, Rana Damsees, Maryam El-Atrash, Rayan Bater, Sama Almasri, Faris Tamimi, Lama Abujamous, Hikmat Abdel-Razeq. Family communication and attitude of patients with breast cancer toward positive pathogenic BRCA1 or BRCA2 mutations. A regional perspective [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-09-17.

Breast Cancer Risk Perception of First Degree Female Relatives of Breast Cancer Patients Influences Their Risk Reduction Behaviors: A Pre-Study Assessment

Background: Breast cancer is the second most common cancer affecting women worldwide. There is an increased risk of breast cancer among the first degree relatives. Perceived risk relates to an individual's belief about the probability or likelihood of developing some specified illness. Cancer fatalism is the belief that cancer is predetermined, beyond individual control, and necessarily fatal. Aim: To assess the self-perceived risk of breast cancer and screening and risk reduction behaviors among the first degree female relatives of breast cancer patients. Findings from this study can inform interventions to increase uptake of breast cancer screening services among relatives of breast cancer patients in low- and middle-income countries (LMICs). The results formed a baseline for designing a study on risk perception and risk reduction practices among first degree female relatives of patients diagnosed with breast cancer at Uganda Cancer Institute, Kampala, Uganda. Methods: Review of literature on risk perception and risk reduction practices of first degree relatives of breast cancer patients. We searched through various literature published in PubMed and oncology journals in HINARI published in English. All the studies were conducted among female relatives of breast cancer patients from world. All eligible papers were included in the review. The papers were carefully appraised to identify key outcomes of the studies. Results: Women were engaged in risk reduction behaviors like smoking cessation, reduction in alcohol intake, physical activity and screening for breast cancer. Women aged 54 years and below had a higher perceived lifetime risk of breast cancer (39.5%) compared with those aged ≥ 55 years (30.6%) who perceived themselves at lower risk. Levels of education have also been found key in determining an individual's perceived risk. Being unrealistically optimistic was significantly associated with high level of educational attainment while women who did not know their risk were less educated. Socioeconomic status has also been seen to influence breast cancer perceived risk. Unrealistic pessimism was frequent among women with a higher income status although a greater proportion of women who accurately perceived their 5-year risk of breast had a higher annual income. There was a significant association of the stage of breast cancer, time since diagnosis and perceived breast cancer risk among the relatives. Fatalistic beliefs about cancer prevention influenced prevention behaviors by promoting a sense of external locus of control changing beliefs about the value of specific behaviors, or reducing self-efficacy and motivation to perform prevention behaviors. Conclusion: High risk perception is associated with increase need to engage in risk reduction behaviors. Fatalism among women was the primary reason not to engage in breast cancer screening.

THE FEATURES OE CLINICAL AND LABORATORY DIAGNOSIS OF FABRY DISEASE

The aim of the study was to determine the clinical features and molecular genetic patterns of patients with Fabry disease (FD) to optimize the diagnostic stepwise.
 Object and methods. The comparison of clinical features was performed and the activity of lysosomal enzyme a–galactosidase A in the peripheral blood leukocyte homogenate was studied in 120 male with the neuropathic pain or acroparesthesia who contacted the Center of Orphan Diseases of NSCH “Ohmatdyt” in years 2002–2016. The cascade family screening (in 8 people) at low enzyme levels and molecular genetic analysis for the presence of mutations in the GLA gene were performed.
 Results. The activity of –galactosidase A was decreased (range 0.5–12.6 nM/mg/h with median 2.0 nM/mg/h) in nine cases (7.5%). All these patients had additional clinical signs (angiokeratoma, hypertrophic cardiomyopathy, coarse facial features, and compromised family tree). The diagnosis of FD were confirmed by the molecular genetic analysis in the GLA gene; there were identified two new mutations (p.739 740delAA and C.945 946delinsTTGA). The other mutations in 6 out of 8 examined families were revealed by the screening of the first kinship degree female relatives, but the activity of –galactosidase A in leukocytes was only reduced in 4 of them.
 Conclusion. The multisystem lesions and the difference in the clinical signs of FD complicate the timely formulation of diagnosis. Selective screening among patients with renal insufficiency, cardiac pathology, and ischemic stroke in the anamnesis increases the possibility of FD diagnosis. Cascade family screening of FD patients relatives is highly effective in identification new patients with non–classical form of FD. Inclusion in the selective group of persons with chronic diseases, compromised pedigree, acroparesthesia and additional FD probable clinical signs reduces the range ofpatients for further high–cost testing and optimizes the diagnosis of FD.

English

BACKGROUND & OBJECTIVES: Patients with Rheumatoid Arthritis (R.A.) have a marked increase in Carotid Atherosclerosis independent of traditional risk factors like family history of myocardial infarction in first degree male relatives younger than 55 years of age or first degree female relatives younger than 65 years of age, smoking, hypertension (Defined as blood pressure of 140/90 mm hg or higher), diabetes mellitus and fasting serum cholesterol levels including age. Chronic inflammation and possibly disease severity and duration are atherogenic in Rheumatoid Arthritis patients. Preclinical disease may also be identified by using ultrasonography to determine carotid intimal-media thickness, an indirect measure of atherosclerosis. The common carotid artery Intima media thickness in Rheumatoid Arthritis patients is positively associated with disease duration, Early Rheumatoid Arthritis (Duration less or = 1 year) is associated with lesser Intima media thickness than was Rheumatoid Arthritis of longer duration. Increased carotid artery Intima media thickness and the presence of carotid plaque are associated with markers of systemic inflammation in patients with Rheumatoid Arthritis and in healthy subjects. OBJECTIVE OF THE STUDY: To determine preclinical atherosclerosis occurring prematurely in patients of Rheumatoid Arthritis by ultrasonograhic measurement Common Carotid Artery Intima media thickness and to evaluate the risk factors associated with arterial intima media thickness in patient of Rheumatoid Arthritis. RESULTS: In RA patients, common carotid artery IMT was significantly higher when compared to healthy controls (0.65 ± 0.06 v/s 0.57 ± 0.049) and was significantly associated with the duration of RA, swollen joint count and erosive changes on hand x-ray independently of other confounding variables. CONCLUSION: Patients with rheumatoid arthritis have a marked increase in carotid atherosclerosis independent of traditional risk factors, including age. Carotid ultrasonography is a simple and inexpensive way of identifying preclinical atherosclerosis in this highly vulnerable population. In addition to prospective management of traditional risk factors, there is a need for aggressive control of rheumatoid arthritis disease activity because chronic inflammation is a driving force for premature atherosclerosis.

<b>Risk assessment for breast cancer and BRCA mutations in women with personal and familial history</b> - doi: 10.4025/actascihealthsci.v35i2.12134

Risk estimation tools can be used in clinical practice to promote the counseling, prevention, or increase the surveillance against breast cancer development. The present study aimed to estimate the risk for breast cancer and the odds for BRCA1/2 mutations, and to correlate the values found by the different models. Breast cancer risk was determined by the models of Gail, Claus, BRCAPRO and Boadicea; and for the mutations, Myriad II, Penn II BRCAPRO, and Boadicea models were utilized, in women who have or had the disease (n = 16) and their respective first degree female relatives unaffected (n = 25). Considering non affected women 16% were categorized as high risk for breast cancer development in five years by the Gail model, and all values presented significant correlation among the models (p < 0.05). Among the participants, 12% (5/41) were considered high risk for BRCA mutations. All the models presented significant correlation between the odds of BRCA1/2 mutation risk, except between Myriad II and Boadicea models. Since there is no model that includes all the variables influencing the development of this disease, it is essential to estimate the risk by more than one model before initiating any clinical intervention.

876 “VOIDING DYSFUNCTION PHENOTYPING OF WOMEN WITH CHRONIC PELVIC PAIN SYNDROMES: RESULTS FROM THE ICEPAC TRIAL”

You have accessJournal of UrologyInfections/Inflammation of the Genitourinary Tract: Interstitial Cystitis1 Apr 2013876 “VOIDING DYSFUNCTION PHENOTYPING OF WOMEN WITH CHRONIC PELVIC PAIN SYNDROMES: RESULTS FROM THE ICEPAC TRIAL” Elias Veizi, Adonis Hijaz, Firouz Daneshgari, and Thomas Chelimsky Elias VeiziElias Veizi Cleveland, OH More articles by this author , Adonis HijazAdonis Hijaz Cleveland, OH More articles by this author , Firouz DaneshgariFirouz Daneshgari Cleveland, OH More articles by this author , and Thomas ChelimskyThomas Chelimsky Milwaukee, WI More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.445AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Interstitial cystitis/Bladder pain syndrome (IC/BPS) and myofascial pelvic pain (MPP) are two of the most common forms of chronic pelvic pain (CPP). Cross organ sensitization in pelvis complicates the clinical diagnosis and treatment of IC/PBS as part of general CPP. ICEPAC trial aims to study the autonomic nervous dysfunction in patients with interstitial cystitis and myofascial pain and aims to assess the signature phenotypes of pain and voiding dynamic changes. METHODS ICEPAC supported by NIH-NIDDK was designed by an interdisciplinary team. Enrollment will include 76 women with IC, 76 women with myofascial pelvic pain disorder (MPP), 38 1st degree female relatives of IC subjects without pelvic pain, and 38 healthy age-matched women. Besides a detailed screening visit with comprehensive assessment of dysautonomias, pain intensity and disability scores, voiding dysfunction phenotype is assessed by Uroflow and a voiding diary. VAS scores, frequency, voiding volumes, flow parameters and timed flow assessment data are collected and analyzed. RESULTS This preliminary analysis includes the first 60 patients [29 healthy control (con) subjects; 23 IC/BPS patient and 8 chronic MPP]. Subjects enrolled in the study are age matched [con 40±15, IC 39.6±15, MPP 40.5±14 yo]. BMI in MPP patients is significantly higher than Hcon and IC subjects [42±5 vs 26±9 in con and 27±8 in IC]. Voiding volumes were lower in the IC group vs H con and MPP whether frequency was higher in the IC group with similar fluid intake. The peak flow [Qmax] was significantly lower in the IC cluster 16±2 ml/sec vs. 28±11 con, 23±4 MPP; while the average flow rate was lower in both IC and MPP vs. con. Similarly duration of flow was higher in IC and MPP vs. con. CONCLUSIONS This preliminary quantitative evaluation of voiding diary and uroflow metrics reveals distinct voiding phenotypes in IC and MPP. The decrease in Qmax in IC cluster in comparison to con and MPP could be an indication of the internal sphincter autonomic dysfunction while the prolonged voiding duration and avg flow in MPP patients could indicate external sphincter hypertonicity [incomplete relaxation]. Further details on voiding dysfunction could lead toward a better understanding of the pathogenesis in IC vs other pelvic floor dysfunction syndromes. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e361-e362 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Elias Veizi Cleveland, OH More articles by this author Adonis Hijaz Cleveland, OH More articles by this author Firouz Daneshgari Cleveland, OH More articles by this author Thomas Chelimsky Milwaukee, WI More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

BRCA 1 and 2 Mutations in Sudanese Secondary School Girls with Known Breast Cancer in Their Families

Breast cancer is a major cause of morbidity and mortality in women worldwide. In Sudan, it is the most commonly diagnosed cancer. This study assesses the prevalence of BRCA1 and BRCA2 mutations among female students with a family history of breast cancer, in secondary schools of Marawi Locality, Northern State, Sudan. From a survey of 2370 students, 67 cases (47 with family history and 20 controls) were analyzed for BRCA1 and BRCA2 mutations with a single-stranded conformation polymorphism (SSCP) mutation detection method applied to peripheral blood. Eighteen subjects knew of first degree female relatives with breast cancer, 23 with second degree female family members affected and 6 with related male sufferers. Twenty randomly selected girls from the remainder of the survey population with no known family history were also tested. The breast cancer susceptibility genes BRCA1 and BRCA2 accounted, respectively, for 1.21% of responders or 51% of those claiming a family history. Mutations were found in 20% of the group selected with no family history. Only 2 BRCA 2 mutations were found, both in girls with no known afflicted relatives. Six girls knew of male relatives with breast cancer; five of these girls carried mutant BRCA 1. Most of the BRCA1- mutations located to exon 11 fragments 11.9 and 11.1. The study indicates a high prevalence of genetically associated breast cancer in the Marawi locality suggesting a need to focus on the two mutation sites in developing screening protocols for at least this area of Sudan.

Presymptomatic breast cancer in Egypt: role of BRCA1 and BRCA2 tumor suppressor genes mutations detection

BackgroundBreast cancer is one of the most common diseases affecting women. Inherited susceptibility genes, BRCA1 and BRCA2, are considered in breast, ovarian and other common cancers etiology. BRCA1 and BRCA2 genes have been identified that confer a high degree of breast cancer risk.ObjectiveOur study was performed to identify germline mutations in some exons of BRCA1 and BRCA2 genes for the early detection of presymptomatic breast cancer in females.MethodsThis study was applied on Egyptian healthy females who first degree relatives to those, with or without a family history, infected with breast cancer. Sixty breast cancer patients, derived from 60 families, were selected for molecular genetic testing of BRCA1 and BRCA2 genes. The study also included 120 healthy first degree female relatives of the patients, either sisters and/or daughters, for early detection of presymptomatic breast cancer mutation carriers. Genomic DNA was extracted from peripheral blood lymphocytes of all the studied subjects. Universal primers were used to amplify four regions of the BRCA1 gene (exons 2,8,13 and 22) and one region (exon 9) of BRCA2 gene using specific PCR. The polymerase chain reaction was carried out. Single strand conformation polymorphism assay and heteroduplex analysis were used to screen for mutations in the studied exons. In addition, DNA sequencing of the normal and mutated exons were performed.ResultsMutations in both BRCA1 and BRCA2 genes were detected in 86.7% of the families. Current study indicates that 60% of these families were attributable to BRCA1 mutations, while 26.7% of them were attributable to BRCA2 mutations. Results showed that four mutations were detected in the BRCA1 gene, while one mutation was detected in the BRCA2 gene. Asymptomatic relatives, 80(67%) out of total 120, were mutation carriers.ConclusionsBRCA1 and BRCA2 genes mutations are responsible for a significant proportion of breast cancer. BRCA mutations were found in individuals with and without family history.

Varying Levels of Family History of Breast Cancer in Relation to Mammographic Breast Density (United States)

We examined the relationship between breast cancer family history and mammographic breast density. Participants included 35,019 postmenopausal women aged >or=40 years enrolled in a population-based mammography screening program. We collected data on the number and type of 1st and 2nd degree female relatives with a history of breast cancer and their ages at diagnosis. We used the Breast Imaging Reporting and Data System breast density categories to identify women with fatty (1 = almost entirely fatty or 2 = scattered fibroglandular tissue) and dense (3 = heterogeneously dense or 4 = extremely dense) breasts. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals for dense (N = 18,111) compared to fatty breasts (N = 16,908). The odds of having dense breasts were 17% greater for women with affected 1st degree relatives than women with no family history. The odds increased with more affected 1st degree relatives [>or=3 vs. none (OR = 1.46; 1.05-2.01)] and among women with >or=1 affected 1st degree relative diagnosed <50 years (OR = 1.22; 1.10-1.34). Having a family history of breast cancer was more strongly associated with mammographic breast density when the affected relatives were more genetically similar. There may be common, yet undiscovered, genetic elements that affect breast cancer and mammographic breast density.

A reduced IL2R (CD25) expression level in first and second degree female relatives of autoimmune thyroid disease patients. A sign of a poor capability to preserve tolerance?

There is room for immune markers other than TPO-Abs to identify an increased risk to develop autoimmune thyroid disease (AITD). Our aim was to test the hypothesis that activation of CD4+T cells is such marker in relatives of AITD patients, who have an increased risk to develop AITD.We established a controlled study on 20 TPO-Ab positive and 20 TPO-Ab negative euthyroid female relatives. All these cases had at least one 1st or 2nd degree relative with a documented autoimmune hyper- or hypothyroidism in whom we studied the percentages of circulating subsets of activated (MHC class-II, CD25 (IL-2R), CD71 or CD69+) CD4+T cells and the level of the soluble (s)-IL2R in serum.We found that euthyroid female relatives did not show an activation of their T cell system, but a reduced expression of CD25 on CD4+T cells. The level of the shed IL2R in serum was also lower in comparison with levels found in healthy control females. A reduced T cell activity was found in both TPO-Ab positive and negative relatives.In conclusion, female relatives with at least one 1st or 2nd degree relative with an AITD show signs of a reduced expansion capability of their T cell pool. It is hypothesized that this reduced expansion capability may affect T cell tolerance mechanisms more than T effector mechanisms.

Cancer burden in women with hereditary non-polyposis colorectal cancer (HNPCC)

9624 Background: Lifetime cancer burden is significant for men and women with HNPCC. In addition to cancers of “other sites” women with HNPCC are estimated to have a 40–60% lifetime risk of developing uterine cancer and an up to 10% lifetime risk of developing ovarian cancer. Methods: Cancer diagnoses of Australian (Victorian) women with HNPCC were reviewed to determine the frequency of cancer and the frequency of gynaecological compared to “other” cancer diagnoses. Female mutation carriers were identified from Familial Cancer Centre database records. From pedigrees first degree female relatives of mutation positive females who had been diagnosed with HNPCC related cancers, and female obligate HNPCC mutation carriers were also identified. Verified cancer diagnoses of these women were recorded. Results: 107 women from 50 families were included. Twenty-four women (22%) belonged to families with an MLH1 mutation, 79 (74%) to families with an MSH2 mutation and 4 (4%) had MSH6 mutations. Twenty-three women (21%) were unaffected by cancer at a median age of 37 years (range 20–88 years). Only five of these were over 40 years of age. Of the women diagnosed with cancer (N=84 or 79%), 50/84 (60%) had colorectal cancer with a median age at first diagnosis of 39 years (range 29–80 years); 32/84 (38%) had CRC only. Thirty-six of 84 (43%) had a gynaecological cancer; 29/84 (35%) had endometrial cancer diagnosed at a median age of 51 (range 39–71 years) and 5/84 (6%) had ovarian cancer (all diagnosed < 50 years of age).Twenty of 84 women with cancer (23%) had a gynaecological cancer alone (15 endometrial, 5 ovarian). Fifteen of 84 women (18%) had both CRC and uterine cancer. Twelve of 107 women (11%) had had prophylactic hysterectomy and oophorectomy. Of 84 women diagnosed with cancer 23 (27%) had more than one cancer and 11 (13%) had 3 or more. Of those with cancer 10 (12%) had breast cancer, 5 (6%) had stomach cancer, 3 (4%) had small bowel cancer, 3 (4%) had transitional cell carcinomas of the urinary tract, 4 (5%) had Muir Torre syndrome and 1 (1%) had a primary brain tumour. Conclusions: Cancer burden in women with HNPCC is significant due to the combination of gynaecological cancers, as well as CRC and cancers of “other” sites; however CRC remains the commonest primary cancer site. No significant financial relationships to disclose.

Review: breast cancer is associated with a family history of the disease in first degree relatives

Collaborative Group on Hormonal Factors in Breast Cancer. Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58 209 women with breast cancer and 101 986...

Familial cancer history in patients with carcinoma of the cervix uteri

Objectives: Several cancers show the tendency to aggregate in families. But the contribution of heredity to the causation of sporadic malignancies, like cervical cancer is unclear. Study Design: Seven hundred and thirty-seven women with operative treated cervical cancer (CX) were searched for familiar history of malignant tumours. Positive familial history was stated, if one first degree relative was affected by malignant tumour. The site of malignant tumour was stated and the mean age was compared. Results: Twenty-two percent of the women had malignancies at different sites in first degree relatives. In about one-half the mother, in 30% the father and in 11% more than one first degree relative was affected. Overall, first degree relatives of 21 patients (13%) had malignancies of the lungs or the oro-pharynx. Thirty-seven women had malignant tumours of the lower genital tract and 11 had invasive cervical cancer. Mean age of patients with positive familial history was the same as those without (43 versus 42 years) it. But, women whose first degree female relatives had cervical cancer were significantly younger than those with extragenital malignancies (37 versus 45 years). The mean 5-year survival rate was higher in patients with a positive familial cancer history (85.6% versus 74.6%; P=1.7). Conclusions: The data suggest, that a small number of patients have a familial susceptibility for cervical cancer and probably for HPV-associated neoplasms. Further studies establishing the immune status and the search for genetic polymorphisms of these patients are required.

Spectrum of inherited bleeding disorders from Western India.

The study was undertaken to assess the magnitude and diversity of different bleeding disorders in Western India. 768 cases referred to our Institute for evaluation of an underlying bleeding diathesis were investigated appropriately to detect the cause of the abnormal hemostatic function. 630 patients were diagnosed to have hereditary bleeding diathesis. Amongst these, 598 patients had a coagulation disorder while only 32 patients had a platelet function abnormality. Amongst the coagulation disorders, hemophilia A (70.5%) was the most common disorder followed by hemophilia B (14%) and VWD (10.8%). Glanzman's thrombasthenia (84.3%) was the most common platelet function disorder followed by Bernard-Soulier syndrome (12.5%). Some rare disorders have also been diagnosed. In spite of their apparent rarity, India has a substantial number of cases of inherited bleeding disorders. A large number of these patients is referred to many tertiary care institutions. It is therefore desirable that district hospitals must develop their laboratories to detect most of these disorders so that the patients need not travel long distances to get an appropriate diagnosis and proper management. All 1st degree female relatives of severe and moderate hemophilia must get factor assays done because some of them may be vulnerable to post-procedural or post-traumatic bleeding.

Risk assessment in first degree female relatives of breast cancer patients using the alkaline Comet assay

First degree female relatives (FDFRs) of breast cancer patients have been reported to have a 2- to 3-fold increase in breast cancer risk as compared with the general population. Assessment of genetic instability (DNA damage and repair efficiency) is an important parameter concerning mutagenesis and carcinogenesis. In an attempt to identify individuals at high risk of breast cancer in the FDFRs of breast cancer patients, two tests were used: the alkaline Comet assay on leucocytes and the micronucleus test (MNT) on buccal epithelial cells. In addition to FDFRs, two other categories of subjects were included: breast cancer patients and controls. The Comet assay was used to study basal DNA damage, DNA susceptibility to a mutagen (N-methyl N-nitro N-nitrosoguanidine) and DNA repair efficiency. In addition, the MNT served as an indicator of chromosome breakage/aneuploidy. A significant increase in DNA damage (basal and after treatment with a mutagen, as well as after allowing repair to take place) and micronucleus frequency was observed from controls to FDFRs and from FDFRs to breast cancer patients. There was considerable variability in the subjects with respect to both of these parameters. Outliers identified among the FDFRs based on 3 SD limits of DNA damage and micronucleus frequency were considered as high risk individuals.

DNA repair proficiency: a potential marker for identification of high risk members in breast cancer families

Breast cancer is the single largest cancer and causes the high rate of cancer mortality among women. A positive family history of breast cancer is recognized as one of the major risk factors for this disease. The present study evaluates bleomycin (BLM)-induced chromosome sensitivity analysis in breast cancer families which provides indirectly a measure of the DNA repair defect of each person. BLM sensitivity assay on cultured lymphocytes of 36 familial breast cancer patients, their 85 first or second degree female relatives, 36 sporadic breast cancer patients and 40 age- and sex-matched controls (without any family history of cancer) were carried out to measure interindividual variation in their DNA repair capacity through mutagen-induced chromosome sensitivity analysis. Fifty percent of familial breast cancer patients and seven unaffected relatives showed hypersensitivity. Compared to hyposensitive relatives these seven subjects may be considered as high risk individuals.

Evidence for a Single Gene Effect Causing Polycystic Ovaries and Male Pattern Baldness

Carey, A. H.; Chan, K. L.; Short, F.; White, D.; Williamson, R.; Franks, S. Author Information

Serum bioactive lactogenic hormone levels in women with familial breast cancer and their relatives

Serum levels of bioactive lactogenic hormone (BLH), immunoreactive prolactin and growth hormone (ir-PRL and ir-GH) were measured in a group of familial breast cancer patients and their first degree female relatives and compared to those found in normal healthy women. The ratio of BLH to the sum of ir-PRL and ir-GH was slightly but significantly decreased in the familial breast cancer group (P = 0.018 by the Mann-Whitney U test) although there were no significant differences in the levels of BLH, ir-PRL and ir-GH between the two groups. No differences in the levels of the lactogenic hormones could be detected when the pre-menopausal women were considered separately or when 20 women from the familial group were compared to normal controls matched for age, parity, weight and menopausal status. The levels of BLH were highly correlated with the sum of ir-PRL and ir-GH in both the familial breast cancer group and the controls (P < 0.001 for both groups by Spearman's rank correlation test). These findings are not indicative of the presence of an additional species of bioactive, but not immunoreactive, lactogen in the sera of women with or at high risk of breast cancer. However, the presence of different, but equipotent, forms of lactogen cannot be excluded in these women.

Menkes X linked disease: heterozygous phenotype in uncloned fibroblast cultures.

The 64Cu incorporation into uncloned fibroblast cultures from 16 Menkes disease mothers and 19 first and second degree female relatives was examined. The mean incorporation for the Menkes disease mothers (36.2 +/- 3.6 SEM) differed significantly from that of 25 normal subjects (21.7 +/- 0.9 SEM) suggesting the presence of a significant proportion of mutant cells. In addition, the results suggested a heterozygous state in a number of the female relatives. Uncloned fibroblast cultures from four Menkes disease heterozygotes showed increasingly abnormal copper uptake values after repeated freezing procedures. Manipulation of tissue cultures may help to identify a number of female carriers.