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%

A systematic review of midwife led interventions to address post traumatic stress syndrome

Objective
to systematically identify interventions that midwives could introduce to address post-traumatic stress in women following childbirth.

Methods
a search strategy was developed and relevant papers were identified from databases including Cinahl, Cochrane Library, EMBASE, Maternity and Infant Care, MEDLINE, PsycINFO, and Web of Science. Key search terms used were post-traumatic stress, post partum, intervention, controlled trial and review. Papers eligible for inclusion were primary studies and reviews of research published from 2002–2012, focusing on interventions which could be implemented by midwives for the prevention and/or management of PTSD. For primary studies, RCTs, controlled clinical trials, and cohort studies with a control group were eligible. Eligible reviews were those with a specified search strategy and inclusion/exclusion criteria. Methodological quality was assessed using recognised frameworks.

Findings
six primary studies and eight reviews were eligible for inclusion. The majority of included studies or reviews focused on debriefing and/or counselling interventions; however the results were not consistent due to significant variation in methodological quality and use of dissimilar interventions. Two of the reviews considered the general management of post partum PTSD and one broadly covered anxiety during pregnancy and the post partum, incorporating a section on PTSD. The majority of women reported that the opportunity to discuss their childbirth experience was subjectively beneficial.

Conclusions and implications for practice
no evidence-based midwifery interventions were identified from this systematic review that can be recommended for introduction into practice to address PTSD. It is recommended that future research in this area should incorporate standardised interventions with similar outcome measures to facilitate synthesis of results. Further research on interventions used in non-maternity populations is needed in order to confirm their usefulness in addressing post partum PTSD.

A systematic review of midwife-led interventions to address post partum post-traumatic stress