Can multiple SNP testing in BRCA2 and BRCA1 female carriers be used to improve risk prediction models in conjunction with clinical assessment?

Background: Several single nucleotide polymorphisms (SNPs) at different loci have been associated with breast cancer susceptibility, accounting for around 10% of the familial component. Recent studies have found direct associations between specific SNPs and breast cancer in BRCA1/2 mutation carriers. Our aim was to determine whether validated susceptibility SNP scores improve the predictive ability of risk models in comparison/conjunction to other clinical/demographic information.

Increased rate of phenocopies in all age groups in BRCA1/BRCA2 mutation kindred, but increased prospective breast cancer risk is confined to BRCA2 mutation carriers.

Background: To establish, if among unaffected noncarrier relatives in a family with an established BRCA1/2 mutation, there is an increased risk of breast cancer.

Methods: We identified 49 women with breast cancer who were first-degree relatives of a pathogenic mutation carrier among 807 BRCA1/2 families but who tested negative for the specific mutation. A prospective analysis of breast cancer from date of family ascertainment was performed for first-degree relatives of proven BRCA1/2 mutation carriers and compared with population-expected incidence rates.

Risk-reducing surgery increases survival in BRCA1/2 mutation carriers unaffected at time of family referral.

The aim of this study was to establish if risk-reducing surgery (RRS) increases survival among BRCA1/2 carriers without breast/ovarian cancer at the time of family referral. Female BRCA1/2 carriers were identified from the Manchester Genetic Medicine Database. Those patients alive and unaffected at the date of first family ascertainment were included in this study.

Reduced life expectancy seen in hereditary diseases which predispose to early-onset tumors.

There are several hereditary diseases that are a predisposition to early-onset tumors. These include syndromic conditions like neurofibromatosis 1 and 2, von Hippel-Lindau syndrome, Gorlin syndrome, multiple endocrine neoplasia, and familial adenomatous polyposis; and conditions which are usually not possible to diagnose clinically in a single individual, such as Lynch syndrome and BRCA1/2. Understanding of the mortality in hereditary cancer predisposing diseases is important for developing effective disease treatment programs.

Contralateral mastectomy improves survival in women with BRCA1/2-associated breast cancer.

BRCA1/2 mutation carriers with breast cancer are at high risk of contralateral disease. Such women often elect to have contralateral risk-reducing mastectomy (CRRM) to reduce the likelihood of recurrence. This study considers whether CRRM improves overall survival.

Ovarian cancer among 8,005 women from a breast cancer family history clinic: no increased risk of invasive ovarian cancer in families testing negative for BRCA1 and BRCA2.

Background: Mutations in BRCA1/2 genes confer ovarian, alongside breast, cancer risk. We examined the risk of developing ovarian cancer in BRCA1/2-positive families and if this risk is extended to BRCA negative families.

Patients And Methods: A prospective study involving women seen at a single family history clinic in Manchester, UK.

Contralateral breast cancer risk in BRCA1/2-positive families needs to be adjusted for phenocopy rates particularly in second-degree untested relatives.

In the previous issue of Breast Cancer Research, Rhiem and colleagues report contralateral breast cancer risks in relatives of BRCA1/2 mutation carriers as well as those testing negative. The authors quote 25-year risks of 44.1% for BRCA1 and 33.

Life expectancy in hereditary cancer predisposing diseases: an observational study.

Background: Neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), familial adenomatous polyposis (FAP), von Hippel-Lindau syndrome (VHL), and Gorlin syndrome (GS) are single gene diseases that predispose to early onset tumours. Few studies have assessed the effect of these diseases on life expectancy. This study's aim was to assess this effect, and to test the hypothesis that genetic registers increase survival.

Mortality in neurofibromatosis 1: in North West England: an assessment of actuarial survival in a region of the UK since 1989.

Neurofibromatosis 1 (NF1) is a comparatively common autosomal dominant disorder. However, relatively few studies have assessed lifetime risk; and information about the effect of NF1 on mortality remains uncertain. NF1 patients were identified using The North West regional family Genetic Register, which covers the 4.

Nottingham knee osteoarthritis risk prediction models.

Objectives: (1) To develop risk prediction models for knee osteoarthritis (OA) and (2) to estimate the risk reduction that results from modification of potential risk factors.

Method: This was a 12-year retrospective cohort study undertaken in the general population in Nottingham, UK. Baseline risk factors were collected by questionnaire.

Development and validation of self-reported line drawings for assessment of knee malalignment and foot rotation: a cross-sectional comparative study.

Background: For large scale epidemiological studies clinical assessments and radiographs can be impractical and expensive to apply to more than just a sample of the population examined. The study objectives were to develop and validate two novel instruments for self-reported knee malalignment and foot rotation suitable for use in questionnaire studies of knee pain and osteoarthritis.

Methods: Two sets of line drawings were developed using similar methodology.