Single Motherhood in East and West Germany: What Can Explain the Differences?

The share of single mothers is higher in East Germany than in West Germany. Using data from the Socio-Economic Panel (SOEP), we examine two transmission channels leading to single motherhood, namely out-of-partnership births and separations of couples with minor children. Women in East Germany have both a higher probability of out-of-partnership birth and a higher probability of separation. We find no evidence that availability of child care plays a role in the differences between East and West Germany. The differences in single motherhood appear to be rather driven by different gender role models and partially also by economic circumstances

BRCA1 and BRCA2 mutations in a population-based study of male breast cancer

Background: The contribution of BRCA1 and BRCA2 to the incidence of male breast cancer (MBC) in the United Kingdom is not known, and the importance of these genes in the increased risk of female breast cancer associated with a family history of breast cancer in a male first-degree relative is unclear. Methods: We have carried out a population-based study of 94 MBC cases collected in the UK. We screened genomic DNA for mutations in BRCA1 and BRCA2 and used family history data from these cases to calculate the risk of breast cancer to female relatives of MBC cases. We also estimated the contribution of BRCA1 and BRCA2 to this risk. Results: Nineteen cases (20%) reported a first-degree relative with breast cancer, of whom seven also had an affected second-degree relative. The breast cancer risk in female first-degree relatives was 2.4 times (95% confidence interval [CI] = 1.4–4.0) the risk in the general population. No BRCA1 mutation carriers were identified and five cases were found to carry a mutation in BRCA2. Allowing for a mutation detection sensitivity frequency of 70%, the carrier frequency for BRCA2 mutations was 8% (95% CI = 3–19). All the mutation carriers had a family history of breast, ovarian, prostate or pancreatic cancer. However, BRCA2 accounted for only 15% of the excess familial risk of breast cancer in female first-degree relatives. Conclusion: These data suggest that other genes that confer an increased risk for both female and male breast cancer have yet to be found

Performance of high-throughput DNA quantification methods

BACKGROUND: The accuracy and precision of estimates of DNA concentration are critical factors for efficient use of DNA samples in high-throughput genotype and sequence analyses. We evaluated the performance of spectrophotometric (OD) DNA quantification, and compared it to two fluorometric quantification methods, the PicoGreen(® )assay (PG), and a novel real-time quantitative genomic PCR assay (QG) specific to a region at the human BRCA1 locus. Twenty-Two lymphoblastoid cell line DNA samples with an initial concentration of ~350 ng/uL were diluted to 20 ng/uL. DNA concentration was estimated by OD and further diluted to 5 ng/uL. The concentrations of multiple aliquots of the final dilution were measured by the OD, QG and PG methods. The effects of manual and robotic laboratory sample handling procedures on the estimates of DNA concentration were assessed using variance components analyses. RESULTS: The OD method was the DNA quantification method most concordant with the reference sample among the three methods evaluated. A large fraction of the total variance for all three methods (36.0–95.7%) was explained by sample-to-sample variation, whereas the amount of variance attributable to sample handling was small (0.8–17.5%). Residual error (3.2–59.4%), corresponding to un-modelled factors, contributed a greater extent to the total variation than the sample handling procedures. CONCLUSION: The application of a specific DNA quantification method to a particular molecular genetic laboratory protocol must take into account the accuracy and precision of the specific method, as well as the requirements of the experimental workflow with respect to sample volumes and throughput. While OD was the most concordant and precise DNA quantification method in this study, the information provided by the quantitative PCR assay regarding the suitability of DNA samples for PCR may be an essential factor for some protocols, despite the decreased concordance and precision of this method

Case report: BRCA in the Ashkenazi population: are current testing guidelines too exclusive?

The BRCA1/2 genes account for a significant portion of hereditary breast and ovarian cancers and they are especially prevalent in the Ashkenazi Jewish population. Women who have a mutation can prevent breast and ovarian cancer with surgical intervention. We describe an Ashkenazi Jewish patient who illustrates that current testing criteria are too restrictive, particularly for this population of patients. The patient's sister was diagnosed with breast cancer at age 33; however, she was not a mutation carrier. Based on practice guidelines, the patient was not recommended genetic testing. She subsequently underwent direct-to-consumer (DTC) testing and discovered that she was a mutation carrier. This case demonstrates the need for clinicians to be aware of the higher prevalence of BRCA mutations in the Ashkenazi population. It also exemplifies the need to involve medical professionals, including genetic counselors, in the dissemination of DNA test results

A common founder for the V126D CDKN2A mutation in seven North American melanoma-prone families

One of the most common melanoma-related CDKN2A mutations reported in North America is the V126D mutation. We examined nine markers surrounding CDKN2A in three American and four Canadian families carrying the V126D mutation. All seven families had a haplotype consistent with a common ancestor/founder for this mutation. In addition, the mutation appears to have originated 34–52 generations ago (1-LOD-unit support interval 13–98 generations). © 2001 Cancer Research Campaign http:///www.bjcancer.co

African ancestry and higher prevalence of triple-negative breast cancer

BACKGROUND: The study of breast cancer in women with African ancestry offers the promise of identifying markers for risk assessment and treatment of triple-negative disease. METHODS: African American and white American women with invasive cancer diagnosed at the Henry Ford Health System comprised the primary study population, and Ghanaian patients diagnosed and/or treated at the Komfo Anokye Teaching Hospital in Kumasi, Ghana constituted the comparison group. Formalin-fixed, paraffin-embedded specimens were transported to the University of Michigan for histopathology confirmation, and assessment of estrogen and progesterone receptors and HER-2/ neu expression. RESULTS: The study population included 1008 white Americans, 581 African Americans, and 75 Ghanaians. Mean age at diagnosis was 48.0 years for Ghanaian, 60.8 years for African American, and 62.4 for white American cases ( P = .002). Proportions of Ghanaian, African American, and white American cases with estrogen receptor-negative tumors were 76%, 36%, and 22%, respectively ( P < .001), and proportions with triple-negative disease were 82%, 26%, and 16%, respectively ( P < .001). All Ghanaian cases were palpable, locally advanced cancers; 57 (76%) were grade 3. A total of 147 American women were diagnosed as stage III or IV; of these, 67.5% (n = 46) of African Americans and 44.6% (n = 29) of white Americans were grade 3. Among palpable, grade 3 cancers, Ghanaians had the highest prevalence of triple-negative tumors (82.2%), followed by African Americans (32.8%) and white Americans (10.2%). CONCLUSIONS: Our study demonstrates progressively increasing frequency of estrogen receptor-negative and triple-negative tumors among breast cancer patients with white American, African American, and Ghanaian/African backgrounds. This pattern indicates a need for additional investigations correlating the extent of African ancestry and high-risk breast cancer subtypes. Cancer 2010. © 2010 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78243/1/25276_ftp.pd

Analysis of alternative lengthening of telomere markers in BRCA1 defective cells

Telomeres are specialized structures responsible for the chromosome end protection. Previous studies have revealed that defective BRCA1 may lead to elevated telomere fusions and accelerated telomere shortening. In addition, BRCA1 associates with promyelocytic leukemia (PML) bodies in alternative lengthening of telomeres (ALTs) positive cells. We report here elevated recombination rates at telomeres in cells from human BRCA1 mutation carriers and in mouse embryonic stem cells lacking both copies of functional Brca1. An increased recombination rate at telomeres is one of the signs of ALT. To investigate this possibility further we employed the C-circle assay that identifies ALT unequivocally. Our results revealed elevated levels of ALT activity in Brca1 defective mouse cells. Similar results were obtained when the same cells were assayed for the presence of another ALT marker, namely the frequency of PML bodies. These results suggest that BRCA1 may act as a repressor of ALT.We acknowledge Dr Amir Hassan-Khani from Bent-Al-Hoda Hospital Mashhad, Iran, for partly funding Parisa K Kargaran. Supported in part by a grant from the DoReMi consortium, EC

Estimating the survival benefits gained from providing national cancer genetic services to women with a family history of breast cancer

The aim of this paper is to compare a service offering genetic testing and presymptomatic surveillance to women at increased risk of developing breast cancer with its predecessor of no service at all in terms of survival and quality-adjusted survival (QALYs) by means of a Markov cohort chain simulation model. Genetic assessment and presymptomatic care provided between 0.07-1.61 mean additional life years and 0.05-1.67 mean QALYs over no services. Prophylactic surgery and surveillance extended mean life expectancy by 0.41-1.61 and 0.32-0.99 years, respectively over no services for high-risk women. Model outcomes were sensitive to all the parameters varied in the sensitivity analysis. Providing cancer genetic services increase survival and as long as services do not induce adverse psychological effects they also provide more QALYs. The greatest survival and QALY benefits were found for women with identified mutations. As more cancer genes are identified, the survival and cost-effectiveness of genetic services will improve. Although mastectomy provided most additional life years, when quality of life was accounted for oophorectomy was the optimal strategy. Delayed entry into coordinated genetic services was found to diminish the average survival and QALY gains for a woman utilising these services