First-degree Relatives Of Women Research Articles

Cancer risks among first-degree relatives of women with a genetic predisposition to breast cancer.

Associations between germline alterations in women and cancer risks among their relatives are largely unknown. We used women from two Swedish cohorts (KARMA and pKARMA), including 28,362 women with genotyping data and 13,226 with sequencing data. Using Swedish Multi-Generation Register, we linked these women to 133,389 first-degree relatives. Associations between protein-truncating variants (PTVs) in 8 risk genes and breast cancer polygenic risk score (PRS) in index women and cancer risks among their relatives were modeled via Cox regression. Female relatives of index women who were PTV carriers in any of the 8 risk genes had an increased breast cancer risk compared to those of non-carriers (HR1.85, 95% CI: 1.52-2.27), with the strongest association found for PTVs in BRCA1/2. These relatives had a statistically higher risk of early-onset than late-onset breast cancer (P = .001). Elevated breast cancer risk was also observed in female relatives of index women with higher PRS (HR per SD: 1.28, 95% CI: 1.23-1.32). The estimated lifetime risk was 22.3% for female relatives of PTV carriers and 14.4% for those related to women in the top PRS quartile. Moreover, relatives of index women with PTV presence (HR: 1.30, 95% CI: 1.06-1.59) or higher PRS (HR per SD: 1.04, 95% CI: 1.01-1.07) were also at higher risk of non-breast-HBOC cancers, including prostate, ovarian, pancreatic cancer, and melanoma. Both PTVs of risk genes and higher PRS in index women are associated with an increased risk of breast and other HBOC-related cancers among relatives.

Familial clustering of intrahepatic cholestasis of pregnancy: a nationwide population-based study in Denmark.

Genetics plays a role in the pathogenesis of intrahepatic cholestasis of pregnancy (ICP); however, empirical evidence on familial clustering of ICP is scarce. We aimed to assess the extent of familial recurrence of ICP. This population-based cohort study included all 668,461 primiparous women who gave birth between 1995 and 2018 in Denmark. Women diagnosed with ICP were included to the index cohort. Kinship with index women was determined with the Danish Civil Registration System. Log-binomial regression was used to calculate the relative recurrence risk (RRR) of ICP in relatives of index women. A total of 6722 (1.0%) primiparous women were diagnosed with ICP. In co-twins (n=57), first-degree (n=2279), second-degree (n=1373), and third-degree (n=1758) relatives of the index women, the incidence of ICP reached 5.3%, 2.6%, 0.7%, and 1.4%, respectively, corresponding to adjusted RRRs of 4.82 (95% CI, 1.60-14.48), 2.54 (1.98-3.26), 0.81 (0.44-1.51), and 1.15 (0.77-1.71), respectively. The first-degree relatives of women who had recurrent ICP or first-trimester ICP seemed to be at higher risks [RRR, 4.30 (2.85-6.48), 3.04 (1.93-4.77), respectively]. A minor increased risk was observed in nonbiological relatives [RRR, 1.35 (1.05-1.73); n=4274, including women's full-brothers' partner and women's husbands' full sisters]. Co-twins and first-degree relatives of ICP patients were at ~5- and ~2.5-fold increased risk of ICP, respectively. No increased risk was observed in second-degree and third-degree relatives. Recurrent ICP and first-trimester ICP might indicate a higher degree of family clustering. Further investigation is needed to investigate the increased risk of ICP in nonbiological relatives.

Psychological Determinants of Men's Adherence to Cascade Screening for BRCA1/2.

BRCA1/2 germline mutations predispose carriers to an increased risk of breast, ovarian, prostate, pancreatic, and skin cancer. Men and women are equally likely to pass on or inherit the pathogenic variant. However, there is evidence that male relatives are less involved in cascade screening than female ones. At the same time, little attention has been given to the research on psychological determinants of men’s adherence to cascade screening in BRCA1/2-positive families. Applying some principles of the Health Action Process Approach model, the present research tested a model of relationships on the adherence to BRCA1/2 cascade testing guidelines. The sample comprised 115 men’s first-degree relatives of women with verified germline mutations (Mage = 41.93; SD = 17.27). A pre–post test design was applied. Significant associations emerged between the intention to uptake BRCA1/2 genetic testing and age, parental status, breast cancer risk perception, self-referred outcome expectancies, perceived benefit, coping self-efficacy, and planning. Higher perceived benefit predicted increases in intention, and higher intention and coping self-efficacy predicted increases in planning. Intention was a positive total mediator of the relationship between benefit and planning. On a theoretical level, our findings partially supported the Health Action Process Approach as a valuable model based on which interventions could be developed in the context of cascade screening for BRCA1/2 genetic testing. Those results supported the importance of integrated genetic counselling sessions with a strict collaboration between geneticists and psychologists together with interventions planned to increase men’s self-monitoring ability to support their self-efficacy.

Profile of Daughters and Sisters of Women With Polycystic Ovary Syndrome: The Role of Proband's Glucose Tolerance.

First-degree relatives of women with polycystic ovary syndrome (PCOS) present hormonal and metabolic alterations compared to girls unrelated to PCOS. It is unknown whether glucose intolerance in the PCOS proband confers a more severe metabolic predisposition on their first-degree relatives. To determine whether glucose tolerance status in women with PCOS is associated with worsened glucose metabolism and sex hormone levels in their peripubertal daughters or sisters. Cross-sectional study. Seven academic centers in North America, South America, and Europe. Sixty-four pairs of women with PCOS and their daughters or younger sisters aged between 8 and 14 years were recruited. Twenty-five mothers or older sisters with PCOS were glucose intolerant (GI) and 39 were normal glucose tolerant (NGT). Beta-cell function estimated by the insulin secretion-sensitivity index-2 (ISSI-2) during an oral glucose tolerance test and by the disposition index during a frequently sampled IV glucose tolerance test. Free testosterone and 17-hydroxyprogesterone (17-OHP) levels. Being related to a GI PCOS proband was associated with a lower ISSI-2 (P-value = 0.032) after adjusting for ethnicity, body mass index z-score, and pubertal stage. They also had higher free testosterone (P-value = 0.011) and 17-OHP levels compared to girls with an NGT proband, the latter becoming significant after adjusting for confounders (P-value = 0.040). Compared to first-degree female relatives of women with PCOS and NGT, first-degree relatives of women with PCOS and GI display lower beta-cell function and hyperandrogenemia, putting them at higher risk of GI and PCOS development.

Reminders of cancer risk and pain catastrophizing: relationships with cancer worry and perceived risk in women with a first-degree relative with breast cancer.

First-degree relatives of women with breast cancer may experience increased worry or perceived risk when faced with reminders of their own cancer risk. Worry and risk reminders may include physical symptoms (e.g., persistent breast pain) and caregiving experiences. Women who engage in pain catastrophizing may be particularly likely to experience increased distress when risk reminders are present. We examined the degree to which persistent breast pain and experience as a cancer caregiver were related to cancer worry and perceived risk in first-degree relatives of women with breast cancer (N = 85) and how catastrophic thoughts about breast pain could impact these relationships. There was a significant interaction between persistent breast pain and pain catastrophizing in predicting cancer worry (p = .03); among women who engaged in pain catastrophizing, cancer worry remained high even in the absence of breast pain. Pain catastrophizing also moderated the relationships between caregiving involvement and cancer worry (p = .003) and perceived risk (p = .03). As the degree of caregiving responsibility increased, cancer worry and perceived risk increased for women who engaged in pain catastrophizing; levels of cancer worry and perceived risk remained low and stable for women who did not engage in pain catastrophizing regardless of caregiving experience. The results suggest that first-degree relatives of breast cancer survivors who engage in pain catastrophizing may experience greater cancer worry and perceived risk and may benefit from interventions aimed at reducing catastrophic thoughts about pain.

Metabolic syndrome, hypertension, and hyperlipidemia in mothers, fathers, sisters, and brothers of women with polycystic ovary syndrome: a systematic review and meta-analysis

To provide an evidence-based assessment of metabolic syndrome, hypertension, and hyperlipidemia in first-degree relatives of women with polycystic ovary syndrome (PCOS). Systematic review and meta-analysis. Not applicable. Mothers, fathers, sisters, and brothers of women with and without PCOS. An electronic-based search with the use of PubMed from 1960 to June 2015 and cross-checked references of relevant articles. Metabolic syndrome, hypertension and dyslipidemia, and surrogate markers, including systolic blood pressure (BP), diastolic BP, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. Fourteen of 3,346 studies were included in the meta-analysis. Prevalence of the following was significantly increased in relatives of women with PCOS: metabolic syndrome (risk ratio [RR] 1.78 [95% confidence interval 1.37, 2.30] in mothers, 1.43 [1.12, 1.81] in fathers, and 1.50 [1.12, 2.00] in sisters), hypertension (RR 1.93 [1.58, 2.35] in fathers, 2.92 [1.92, 4.45] in sisters), and dyslipidemia (RR 3.86 [2.54, 5.85] in brothers and 1.29 [1.11, 1.50] in fathers). Moreover, systolic BP (mothers, sisters, and brothers), total cholesterol (mothers and sisters), low-density lipoprotein cholesterol (sisters), and triglycerides (mothers and sisters) were significantly higher in first-degree relatives of PCOS probands than in controls. Our results show evidence of clustering for metabolic syndrome, hypertension, and dyslipidemia in mothers, fathers, sisters, and brothers of women with PCOS. PROSPERO 2016 CRD42016048557.

Breast Cancer Screening Behaviors of First Degree Relatives of Women Receiving Breast Cancer Treatment and the Affecting Factors.

First-degree relatives of women with breast cancer are under higher risk when compared with the general population. The aim of this study is to evaluate breast cancer screening behaviors of women who are first-degree relatives of women with breast cancer and factors affecting these behaviors. This descriptive study included 240 patient relatives, who agreed to participate in the study through contact with first-degree relatives of 133 patients who were receiving breast cancer treatment at the Oncology and Chemotherapy unit of an university hospital in Turkey. Data were collected using the "Descriptive Characteristics Form," which consisted of socio-demographic characteristics, health history, breast cancer risk level and health beliefs as well as the "Breast Cancer Screening Behavior Evaluation Form". Out of the subjects, 17% reported doing breast self examination (BSE), 18% reported getting clinic breast examination (CBE) and 17% reported getting mammography. Logistic regression analysis showed that perceived susceptibility increased BSE by 0.57 times and increased mammography by 0.77 times. Physical exercise increased CBE by 0.21 times and increased mammography by 0.13 times. It was found that women with familial breast cancer history (FBCH) had lower participation in screening behaviors. Higher susceptibility perception and regular physical exercise are the determinant variables. Women with a higher susceptibility can be led towards the screening and their participation can be increased. In women with family history, the development of healthy lifestyle behaviors like physical exercise should be supported.

Setting the Threshold for Surgical Prevention in Women at Increased Risk of Ovarian Cancer.

The number of ovarian cancer cases is predicted to rise by 14% in Europe and 55% worldwide over the next 2 decades. The current absence of a screening program, rising drug/treatment costs, and only marginal improvements in survival seen over the past 30 years suggest the need for maximizing primary surgical prevention to reduce the burden of ovarian cancer. Primary surgical prevention through risk-reducing salpingo-oophorectomy (RRSO) is well established as the most effective method for preventing ovarian cancer. In the UK, it has traditionally been offered to high-risk women (>10% lifetime risk of ovarian cancer) who have completed their family. The cost-effectiveness of RRSO in BRCA1/BRCA2 carriers older than 35 years is well established. Recently, RRSO has been shown to be cost-effective in postmenopausal women at lifetime ovarian cancer risks of 5% or greater and in premenopausal women at lifetime risks greater than 4%. The acceptability, uptake, and satisfaction with RRSO at these intermediate-risk levels remain to be established. Prospective outcome data on risk-reducing salpingectomy and delayed-oophorectomy for preventing ovarian cancer is lacking, and hence, this is best offered for primary prevention within the context and safe environment of a clinical trial. An estimated 63% of ovarian cancers occur in women with greater than 4% lifetime risk and 53% in those with 5% or greater lifetime-risk. Risk-reducing salpingo-oophorectomy can be offered for primary surgical prevention to women at intermediate risk levels (4%-5% to 10%). This includes unaffected women who have completed their family and have RAD51C, RAD51D, or BRIP1 gene mutations; first-degree relatives of women with invasive epithelial ovarian cancer; BRCA mutation-negative women from high-risk breast-and-ovarian cancer or ovarian-cancer-only families. In those with BRCA1, RAD51C/RAD51D/MMR mutations and the occasional families with a history of ovarian cancer in their 40s, surgery needs to be considered at younger than 45. In other moderate-risk gene mutation carriers and those with polygenic risk, RRSO needs be considered at 50. There is need for establishment/expansion of well-defined pathways to increase clinical access to RRSO. It is time to lower the risk threshold for RRSO to enable introduction of a targeted primary prevention approach, which could significantly impact the future burden of ovarian cancer.

Abstract 2548: Cancer in first-degree relatives of women with early-onset breast cancer: a comparison of self-reported and cancer registry data

Abstract Background Breast cancer (BC) is the most common cancer in women, both world-wide and in Sweden. However, only about 2% occur in women ≤35 years of age. The aim of this study was to compare self-reported and registry data of family history of cancer, tumor characteristics and BRCA germline mutation status in women with early-onset BC. Materials and methods Between January 1st 1990 and December 31st 2013, a total of 779 women aged ≤35 years were diagnosed with BC in the South Swedish Health Care Region. Of these women, 231 women sought, or were referred for, genetic counseling at the Oncogenetic Clinic, Lund, Sweden, and were included in the study. Subsequently, 224 women were screened for germline mutations. Self-reported information about family history of cancer in first-degree relatives (parents, siblings and children) was obtained from the participants and was compared with data from the Swedish Cancer Registry. When available, hormone receptor (ER and PR) and HER2 status of the tumors was collected from pathology reports. Fisher's Exact Test was performed to estimate odds ratios (ORs) with 95% confidence intervals (CIs). Results Mutation analyses revealed 143 (63.8%) cases without mutations (BRCAX), 46 (20.5%) with BRCA1, 19 (8.5%) with BRCA2 and 16 (7.1%) with other mutations (TP53, CHEK2, PTEN, PALB2, CDH1 and MSH2/MSH6). Family history of BC and ovarian cancer (OvC) in first-degree relatives was self-reported in equal numbers as registry data. Family history of BC was found in ∼30% of the cases, and of OvC in ∼3%. However, family history of other types of cancer was self-reported in 13 (5.6%) and registry-reported in 58 (25.1%) cases (OR, 18.8; 95% CI, 3.91-180; p<0.001). Of the registry-reported cancers, cervical and skin cancers were the most common when diagnosed before the genetic counseling sessions, and when diagnosed after, prostate and skin cancers were the most common. When comparing tumor characteristics of BRCA1 with BRCAX cases, mutation carriers more often showed receptor negative tumors: ER- (OR, 13.4; 95% CI, 3.77-73.5; p<0.001), PR- (OR, 47.9; 95% CI, 7.34-2011; p<0.001) and HER2- (OR, 17.1; 95% CI, 1.81-inf; p<0.004). Conclusion The main findings in this study of early-onset BC were that cases with germline mutations in the BRCA1 and BRCA2 genes were exceptional high, that cervical cancer was the most common not self-reported cancer in first-degree relatives diagnosed before the genetic counseling, and that BRCA1 carriers had a higher rate of ER, PR and HER2 negative tumors, which tends to indicate a less favorable prognosis. When assessing the need for mutation screening, as shown previously by others, oncologists and genetic counselors need to consider both early-onset BCs and receptor negative tumors as predictors for BRCA1 mutations, and when obtaining information about family history of cancers, patients might lack information about cervical cancers in relatives. Citation Format: Annelie Augustinsson, Ulf Kristoffersson, Håkan Olsson. Cancer in first-degree relatives of women with early-onset breast cancer: a comparison of self-reported and cancer registry data. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2548.

Cardiovascular disease risk in first-degree relatives of women with polycystic ovary syndrome

To assess the risk of cardiovascular disease (CVD) in the parents of polycystic ovary syndrome (PCOS) patients using carotid intima medial thickness (CIMT) and brachial artery flow-mediated dilatation (FMD). Hospital-based case-control study. Endocrine clinic of a medical institute in India. Case group of 41 fathers and 45 mothers of PCOS patients (confirmed by Rotterdam's criteria) compared with 42 men and 44 women matched by age, sex and body mass index (BMI) as controls. CVD risk in parents of PCOS patients assessed via CIMT and FMD then correlated with various clinical and metabolic parameters. Differences in CIMT and FMD between parents and controls. The CIMT was higher [0.6 (0.54-0.8) vs. 0.5 (0.45-0.55) mm] and brachial artery FMD was lower [11.9% (6.9%-16.2%) vs. 16.7% (13.5%-22.6%)] in the parents of PCOS patients as compared with the controls. Systolic blood pressure, diastolic blood pressure, low-density lipoprotein cholesterol, and fasting and 2-hour plasma glucose were higher in the parents of the PCOS patients. The prevalence of CVD risk factors such as systemic hypertension, diabetes mellitus, abdominal obesity, the metabolic syndrome, and a family history of coronary artery disease in first-degree relatives was also higher in the parents of PCOS patients. The prevalence of diabetes was higher in the fathers of PCOS women, but other cardiovascular disease risk factors, CIMT, and FMD were comparable among the mothers. The parents of PCOS patients have an increased CVD risk as evidenced by increased CIMT and low FMD.

Abstract P3-07-07: Familial risk of breast density in extended Utah pedigrees

Abstract Background: Mammographic breast density (MBD) and family history are consistently associated with breast cancer risk, and breast density may account for a proportion of susceptibility to this disease. MBD has been shown to correlate in small cohort studies of twins and siblings. However, MBD has not been studied on a large scale in multi-generation families. We investigated the familial relative risk of MBD in the Utah population, as clustering of breast density in extended relatives may provide evidence for the role of genetics in breast density and inform screening recommendations. Methods: Using the Utah Population Database (UPDB), an extensive genealogical database linked to medical records) we identified 189,812 women ages 35-85 with pedigree information, who underwent digital mammography between 2005-2012, with no history of breast/ovarian cancer and no indication of tamoxifen/aromatase inhibitor use. Individuals with unusually frequent screening (>1/yr) or with inconsistent MBD assessments were not included. Subjects were categorized according to Breast Imaging-Reporting and Data System (BI-RADS®) composition classification at index mammogram available in radiology records of Intermountain Healthcare and University of Utah Healthcare systems, representing the majority of mammograms in Utah, as: (I) 0-25% fibroglandular densities (mostly fat); (II) 26-50% fibroglandular (scattered densities); (III) 51-75% fibroglandular (heterogeneously dense); or, (IV) >75% fibroglandular densities (extremely dense). Familial recurrence risks of MBD classification and breast cancer were estimated using Cox regression models in relatives (mothers, daughters, and sisters or 1st-degree; aunts, nieces, grandmothers, and granddaughters or 2nd-degree; first- and second-cousins) of probands classified as BI-RADS I (N=18,170) or BI-RADS IV (N=11,787), compared to those in the most common classifications, BI-RADS II (N=79,825) and III (N=80,030) combined. Women in the comparison group were randomly selected and matched 5:1 to probands on birth year. Results: Relatives of women with a history of extremely dense breasts (BI-RADS IV) were at increased relative risk (RR) of extremely dense breasts compared to women in BI-RADS II/III: 1st-degree, RR=2.3 (95%CI 2.0-2.7, P<10-15); 2nd-degree, RR=1.8 (95%CI 1.5-2.2, P<10-9); first cousins, RR=1.2 (95%CI 1.1-1.4, P<10-5); and second cousins, RR=1.1 (95%CI 1.06-1.2, P<10-5). Conversely, relatives of women in BI-RADS I (mostly fat) were at decreased risk of BI-RADS IV: 1st-degree, RR=0.5 (95%CI 0.4-0.5, P<10-15); 2nd-degree, RR=0.7 (95%CI 0.6-0.8, P<10-6); first cousins, RR=0.85 (95%CI 0.8-0.9, P<10-4); and second cousins, RR=0.9 (95%CI 0.9-<1.0, P<10-8). First-degree relatives of women in BI-RADS IV were at slightly greater risk of breast cancer compared to women in BI-RADS II/III (RR=1.2, 95%CI 1.1-1.4; P=0.004), while women in category I showed no increased cancer risk. Conclusions: BI-RADS composition categories available from radiology records in the UPDB appear to be useful in assessing familial risk of MBD at the population level. Our results may inform screening guidelines in more distant as well as close relatives of women with a history of extremely dense breasts, whose families may be more susceptible to breast cancer. Citation Format: Karen Curtin, Leigh Neumayer, Matthew B Morgan, Matthew A Stein, Nicola J Camp, Geraldine P Mineau, Kerry G Rowe, Saundra S Buys. Familial risk of breast density in extended Utah pedigrees [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-07-07.

Risk of metabolic syndrome in the first degree relatives of women with polycystic ovarian syndrome

Background: Poly cystic ovarian syndrome (PCOS) is a common disorder, affecting approximately 4 – 8% of women in the reproductive age group. First degree relatives (FDRs) of women with PCOS are at high risk developing endocrine and metabolic co-morbidities of PCOS such as obesity, insulin resistance (IR), and impaired insulin sensitivity, hyperlipidemia and metabolic syndrome (MBS). Present study was conducted with the objectives to evaluate the risk of metabolic syndrome in FDRs of women with PCOS and to compare the risk of metabolic syndrome in FDRs of women with PCOS with age, sex and relation matched FDRs of women with no PCOS. To give suitable recommendations based on the findings of the study. Methods: Hospital based cross sectional analytical study was carried out. 50 FDRs of women with PCOS were compared against same number of age, sex and relation matched FDRs of women with no PCOS. Results: The prevalence of MBS was significantly higher i.e. 34% among FDRs PCOS compared to FDRs Controls (8%) (p < 0.05). The FDRs PCOS were 5.92 times more at risk of MBS than FDRsControls (p < 0.05). Relation wise it was found that the father PCOS and mother PCOS were 1.5 times at risk, brother PCOS were 14.26 and sister PCOS were 12.43 times at risk of MBS than their counterparts. Conclusions: Thus it is concluded that the FDRs PCOS are at high risk of MBS than FDRs Controls .

Risk of Nonsyndromic Cleft Lip and Palate in Relatives of Women With Breast Cancer

Nonsyndromic cleft lip and/or cleft palate (NSCL/P, OMIM119530) is the most common craniofacial birth defect. Epidemiological studies have assessed the relationship between cancer and NSCL/P. This study determined the frequency of NSCL/P in families of women with breast cancer (BC). Five hundred thirty-eight women (246 with BC and 292 without BC) were evaluated. Women from both groups completed a questionnaire concerning their family history of NSCL/P in first-degree relatives. We used chi-square and Fisher's exact tests to determine statistically significant differences between both groups of women (α = 0.05). From the 246 women with BC, two had a positive history of NSCL/P; in the control group, two women had a history of NSCL/P (chi-square with 1 degree of freedom, p = 0.86; Fisher's test, p = 0.37). Thus the frequency of NSCL/P was not significantly increased in the first-degree relatives of women with BC. Acknowledgment: FAPEMIG.

Determination of Information and Support Needs of First Degree Relatives of Women with Breast Cancer

Breast cancer is the most frequent type of cancer among women in the world and the most common cause of deaths from cancer in females. In Turkey, breast cancer comes first in the list of the most frequent ten cancer types seen in women. As the incidence rate of breast cancer is high, many women having breast cancer in the family experience the breast cancer at secondhand. This study was carried out in an attempt to determine the information and support needs of women whose first-degree relatives have breast cancer and to what extent these needs are met. The research sample consisted of 156 women. Questionnaire Form and Information and Support Needs Questionnaires were used as the data collection tools. Information need score averages (x?:3.72±0.19) of women included in the research sampling were found to be higher than their score averages of support needs (x?:3.24±0.41). Information needs which were indicated by women as very important were related to treatment, symptoms of breast cancer and breast self examination (BSE), while support needs which were indicated by women as very important were learning how to perform BSE, women's anxiety for themselves and their relatives regarding breast cancer and having their breasts examined by a health professional. It is recommended that nurses and other medical staff should give information to women whose first-degree relatives have breast cancer about the disease, its etiology, scanning, diagnosis, treatment options and protection as well as prevention.

New insights into the risk of breast cancer in childhood cancer survivors treated with chest radiation: A report from the Childhood Cancer Survivor Study (CCSS) and the Women's Environmental Cancer and Radiation Epidemiology(WECARE) Study.

CRA9513 Background: The risk of breast cancer (BC) by age 50 among women treated for childhood cancer with chest radiation therapy (RT) and how this risk compares with that of BRCA1 and BRCA2 (BRCA1/2) mutation carriers is unknown. Methods: We evaluated the risk of BC in a cohort of 1268 female 5-yr childhood cancer survivors treated with chest RT and estimated the cumulative incidence of BC non-parametrically treating death as a competing risk. The cumulative incidence of BC in BRCA1/2 mutation carriers was estimated with the kin-cohort method using data from 4570 female first-degree relatives of women diagnosed with unilateral BC (probands) participating in the WECARE Study. Absolute Excess Risks (AERs) were estimated using population-based data from the SEER program. Results: With a median follow-up of 26 yrs (range 5-39) for the CCSS cohort, 175 women were diagnosed with BC at a median age of 38 yrs (range 24-53) and a median latency of 23 yrs (range 7-38); the overall cumulative incidence of BC by age 50 was 24% (95% confidence interval [CI] 20-28%) and among Hodgkin lymphoma survivors was 30% (95% CI 25-35%). In comparison, among first-degree relatives of WECARE Study probands 324 were diagnosed with BC (median age at diagnosis, 55 yrs (range 26-90)). The estimated cumulative incidence by age 50 was 31% (95% CI 16-47%) and 10% (95% CI 2-23%) in carriers of BRCA1 and BRCA2 mutations, respectively. The population cumulative incidence of BC is 4% by age 50. Among the childhood cancer survivors, AERs for BCs diagnosed per 10,000 person-years of observation were respectively 34 (95% CI 18-52), 27 (95% CI 11-45), and 95 (95% CI 78-112) among women treated with 10-19 Gy (23%), 20-29 Gy (17%), and 30+ Gy (56%) of chest RT. Conclusions: Women treated for childhood cancer with chest RT have a substantial risk of BC comparable to BRCA1/2 mutation carriers and considerably greater than that of the general population. Women treated with 10-19 Gy RT had an increased excess risk warranting consideration of breast cancer surveillance strategies similar to the current recommendations for women treated with &gt; 20 Gy.

Polycystic ovary syndrome: an ancient disorder?

Polycystic ovary syndrome (PCOS) appears to be an ancient disorder, which has persisted in human evolution despite reduced fecundity because of the benefits to affected women such as greater sturdiness and improved energy utilization, a rearing advantage for their children and kin, and a reduction in the risk of perinatal mortality. This raises the possibility that gene variants that are eventually found to be associated with PCOS will be similar across ethnic groups and races.

Metabolic and reproductive characteristics of first-degree relatives of women with self-reported oligo-amenorrhoea and hirsutism

Objective. To investigate the occurrence of oligo-amenorrhoea and hirsutism, infertility and metabolic morbidity among first-degree relatives of women with and without self-reported oligo-amenorrhoea and hirsutism.Design. Nested case-control study.Setting, population and methods. A postal questionnaire about symptoms of oligo-amenorrhoea and hirsutism was sent to all women of the Northern Finland Birth Cohort 1966 (n = 5889). From this population were randomly selected 98 women with both symptoms and 163 without symptoms. A further questionnaire on the occurrence of oligo-amenorrhoea, hirsutism, infertility, early balding and metabolic morbidity in their relatives was sent to this subpopulation.Main findings. We obtained data on 183 relatives of 43 women with symptoms and 412 relatives of 86 symptomless women. Compared with relatives of symptomless women, mothers of women with symptoms suffered significantly more often from hirsutism and menstrual disorders, and sisters more often from hirsutism and infertility, and had fewer children and were more often childless. There was an increased prevalence of diabetes in the sisters and of hypertension in the fathers of women with symptoms.Conclusions. These results strengthen earlier findings of significantly increased metabolic and reproductive morbidity in the relatives of women with symptoms of PCOS.

First degree relatives of women with breast cancer: who's providing information and support and who'd they prefer

Mothers, sisters, and daughters of women diagnosed with breast cancer have an increased need for factual information, counseling, and emotional support. The purpose of this exploratory, descriptive study was to identify the information and support needs of Israeli women with a family history of breast cancer; discover whether these needs have been met, by whom, and who is the preferred source for them. 128 healthy Israeli women, aged 18-65, with a first degree relative with breast cancer completed the adapted Information and Support Needs Questionnaire (ISNQ). Information needs were ranked above support needs, especially information about disease prevention. The degree to which the needs were met was generally ranked as low, with response to the information needs ranking higher than the response to the support needs. The doctor was the prime source of choice for the information and support needs. This study contributes to the understanding of the needs of patients' families, provides a framework for the improvement of methods of communication, and a basis for constructing information and support systems. In addition, it highlights the need for a multidisciplinary, proactive approach in health promotion for cancer patients' families.

Age-Specific Incidence of Breast Cancer in Breast Cancer Survivors and Their First-Degree Relatives

The incidence rate of breast cancer in first-degree relatives of women with breast cancer has been hypothesized to become constant at a predetermined age in accordance with observations of a high, roughly constant incidence rate of contralateral breast cancer by age. We attempted to test this hypothesis in the Danish population with cancer registry data. We determined the age-specific incidence rates of contralateral breast cancer in Danish women who had a first breast cancer before they were 50 years of age and the rates of breast cancer among their first-degree female relatives during 1943 to 1999. The observed rates were tested for trends chi test or evaluated in Cox proportional hazard models. A high incidence rate of contralateral breast cancer was observed in women aged 25-44 years, followed by a decreasing rate, which reached a level corresponding to the rate per breast in the general female population at age 65. At ages older than the index patients age at diagnosis, their first-degree female relatives showed significantly increasing incidence rates of breast cancer by age, with a relatively constant absolute difference of 187 breast cancers per 100,000 person-years between the observed rates and the expected rates. The rate of contralateral breast cancer is particular high at young ages but the excess ebbs as the cohort ages, perhaps due to elimination of predisposed individuals at early ages from the cohort of survivors. First-degree relatives seem to share breast cancer susceptibility genes with the family proband resulting in a constant excess rate of breast cancer throughout life.

Abdominal fat distribution and insulin resistance in Indian women with polycystic ovarian syndrome

The relationship between insulin resistance and abdominal fat distribution was studied in Indian patients with PCOS. Subcutaneous fat, together with a family history of type 2 diabetes mellitus, was the best marker of insulin resistance.