Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk Prediction

The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for BRCA2 carriers (per-allele HR - 1.10, 95% CI: 1.03-1.18, P - 0.006 and HR - 1.09, 95% CI: 1.01-1.19, P = 0.03, respectively). Neither SNP was associated with breast cancer risk for BRCA1 carriers, and rs6504950 was not associated with breast cancer for either BRCA1 or BRCA2 carriers. Of the 9 polymorphisms investigated, 7 were associated with breast cancer for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, P 7 = 10 x (11) - 0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (P = 0.0049, 0.03, respectively). All risk-associated polymorphisms appear to interact multiplicatively on breast cancer risk for mutation carriers. Based on the joint genotype distribution of the 7 risk-associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e., between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing breast cancer by age 80, compared with 42%

Evaluation of a candidate breast cancer associated SNP in ERCC4 as a risk modifier in BRCA1 and BRCA2 mutation carriers. Results from the Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA)

BACKGROUND: In this study we aimed to evaluate the role of a SNP in intron I of the ERCC4 gene (rs744154), previously reported to be associated with a reduced risk of breast cancer in the general population, as a breast cancer risk modifier in BRCA1 and BRCA2 mutation carriers.

Non-uptake of predictive genetic testing for BRCA1/2 among relatives of known carriers: Attributes, cancer worry, and barriers to testing in a multicenter clinical cohort

BRCA1/2 test decliners/deferrers have received almost no attention in the literature and this is the first study of this population in the United Kingdom. The aim of this multicenter study is to examine the attributes of a group of individuals offered predictive genetic testing for breast/ovarian cancer predisposition who did not wish to proceed with testing at the time of entry into this study. This forms part of a larger study involving 9 U.K. centers investigating the psychosocial impact of predictive genetic testing for BRCA1/2. Cancer worry and reasons for declining or deferring BRCA1/2 predictive genetic testing were evaluated by questionnaire following genetic counseling. A total of 34 individuals declined the offer of predictive genetic testing. Compared to the national cohort of test acceptors, test decliners are significantly younger. Female test decliners have lower levels of cancer worry than female test acceptors. Barriers to testing include apprehension about the result, traveling to the genetics clinic, and taking time away from work/family. Women are more likely than men to worry about receiving less screening if found not to be a carrier. The findings do not indicate that healthy BRCA1/2 test decliners are a more vulnerable group in terms of cancer worry. However, barriers to testing need to be discussed in genetic counseling.

Racism, masculine peer-group relations and the schooling of African/Caribbean infant boys

The past decade has witnessed the publication of a growing number of important ethnographic studies investigating the schooling experiences of Black students. Their focus has largely been upon student-teacher relations during the students' last few years of compulsory schooling. What they have highlighted is the complexity of racism and the varied nature of Black students' experiences of schooling. Drawing upon data from a year-long ethnographic study of an inner-city, multi-ethnic primary school, this paper aims to compliment these studies in two ways. Firstly the paper will broaden the focus to examine how student peer-group relations play an integral role, within the context of student-teacher relations, in shaping many Black students' schooling experiences. By focussing on African/Caribbean infant boys, it will be shown how student-teacher relations on the one hand, and peer-group relations on the other, form a continuous feed-back loop; the products of each tending to exacerbate and inflate the other. Secondly, by concentrating on infant children, the paper will assess the extent to which these resultant processes and practices are also evident for Black pupils at the beginning of their school careers - at the ages of five and six.

Essential and toxic elements in infant foods from Spain, UK, China and USA

Spanish gluten-free rice, cereals with gluten, and pureed baby foods were analysed for essential macro-elements (Ca and Na), essential trace elements (Fe, Cu, Zn, Mn, Se, Cr, Co and Ni) and non-essential trace elements (As, Pb, Cd and Hg) using ICP-MS and AAS. Baby cereals were an excellent source of most of the essential elements (Ca, Fe, Cu, Mn and Zn). Sodium content was high in pureed foods to improve their flavour; fish products were also rich in Se. USA pure baby rice samples had the highest contents of all studied essential elements, showing a different nutrient pattern compared to those of other countries. Mineral fortification was not always properly stated in the labelling of infant foods. Complementary infant foods may also contain significant amounts of contaminants. The contents of Hg and Cd were low enough to guarantee the safety of these infant foods. However, it will be necessary to identify the source and reduce the levels of Pb, Cr and As in Spanish foods. Pure baby rice samples contained too much: Pb in Spain; As in UK; As, Cr and Ni in USA; and Cr and Cd in China.