Effect of decision aid for breast cancer prevention on decisional conflict in women with a BRCA1 or BRCA2 mutation: a multisite, randomized, controlled trial.

PURPOSE: Women with a BRCA1 or BRCA2 mutation are at high risk for breast cancer and must make important decisions about breast cancer prevention and screening. In the current study, we report a multisite, randomized, controlled trial evaluating the effectiveness of a decision aid for breast cancer prevention in women with a BRCA mutation with no previous diagnosis of cancer. METHODS: Within 1 month of receiving a positive BRCA result, women were randomized to receive either usual care (control group) or decision aid (intervention group). Participants were followed at 3, 6, and 12 months; were asked about preventive measures; and completed standardized questionnaires assessing decision making and psychosocial functioning. RESULTS: One hundred fifty women were randomized. Mean cancer-related distress scores were significantly lower in the intervention group compared with the control group at 6 months (P = 0.01) and at 12 months postrandomization (P = 0.05). Decisional conflict scores declined over time for both groups and at no time were there statistical differences between the two groups. CONCLUSION: The decision aid for breast cancer prevention in women with a BRCA1 or BRCA2 mutation is effective in significantly decreasing cancer-related distress within the year following receipt of positive genetic test results.Genet Med 19 3, 330-336.

An anadysplasia-like, spontaneously remitting spondylometaphyseal dysplasia secondary to lamin B receptor (LBR) gene mutations: further definition of the phenotypic heterogeneity of LBR-bone dysplasias.

We describe a boy who has an anadysplasia-like spondylometaphyseal dysplasia. By whole exome sequencing he was shown to have compound heterozygous mutations of LBR that codes for the lamin B receptor. He shares many similarities with a case previously described, but in whom the early natural history could not be established [Borovik et al., 2013]. Thus, in addition to Greenberg dysplasia (a perinatal lethal disorder), homozygosity or compound heterozygosity of mutations in LBR can result in a mild, spontaneously regressing bone dysplasia.

Long-term follow-up of Jewish women with a BRCA1 and BRCA2 mutation who underwent population genetic screening.

There are two mutations in BRCA1 and one in BRCA2, which are present in up to 2.5% of Jewish women. Population genetic testing for Jewish women has been proposed; however, it is unclear how this would impact the uptake of cancer prevention options and psychosocial functioning in women with a positive result. Two thousand and eighty unselected Jewish women were tested for the Jewish BRCA mutations, and 1.1% were positive. Cancer-related distress was measured before testing, and at 1 and 2 years post-testing. Information on uptake of cancer risk reduction options was collected at 2 years. Breast and ovarian cancer risks were estimated using BRCAPRO. Within 2 years of receiving a positive result, 11.1% of women had prophylactic mastectomy, and 89.5% had a prophylactic oophorectomy. The mean breast cancer risk was estimated to be 37.2% at time of testing, compared to 20.9% at 2 years post-testing. The mean ovarian cancer risk was estimated to be 24.5% at time of testing, compared to 7.5% at 2 years following testing. Distress decreased between 1 and 2 years for women with prophylactic mastectomy and oophorectomy (P = 0.02), and for women with prophylactic oophorectomy only (P = 0.04) but not for those with neither surgery. The majority of Jewish women with a BRCA mutation identified through a population screening elected prophylactic oophorectomy, but a few had a prophylactic mastectomy. Uptake of either surgery resulted in decreased distress. Provision of population BRCA testing resulted in reduced risks of breast and ovarian cancers in women with a mutation.

Excessive genomic DNA copy number variation in the Li-Fraumeni cancer predisposition syndrome.

DNA copy number variations (CNVs) are a significant and ubiquitous source of inherited human genetic variation. However, the importance of CNVs to cancer susceptibility and tumor progression has not yet been explored. Li-Fraumeni syndrome (LFS) is an autosomal dominantly inherited disorder characterized by a strikingly increased risk of early-onset breast cancer, sarcomas, brain tumors and other neoplasms in individuals harboring germline TP53 mutations. Known genetic determinants of LFS do not fully explain the variable clinical phenotype in affected family members. As part of a wider study of CNVs and cancer, we conducted a genome-wide profile of germline CNVs in LFS families. Here, by examining DNA from a large healthy population and an LFS cohort using high-density oligonucleotide arrays, we show that the number of CNVs per genome is well conserved in the healthy population, but strikingly enriched in these cancer-prone individuals. We found a highly significant increase in CNVs among carriers of germline TP53 mutations with a familial cancer history. Furthermore, we identified a remarkable number of genomic regions in which known cancer-related genes coincide with CNVs, in both LFS families and healthy individuals. Germline CNVs may provide a foundation that enables the more dramatic chromosomal changes characteristic of TP53-related tumors to be established. Our results suggest that screening families predisposed to cancer for CNVs may identify individuals with an abnormally high number of these events.

Younger age of cancer initiation is associated with shorter telomere length in Li-Fraumeni syndrome.

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome frequently associated with germ line TP53 mutations. Unpredictable and disparate age of cancer onset is a major challenge in the management of LFS. Genetic modifiers, including the MDM2-SNP309 polymorphism, and genetic anticipation have been suggested as plausible explanations for young age of tumor onset, but the molecular mechanisms for these observations are unknown. We speculated that telomere attrition will increase genomic instability and cause earlier tumor onset in successive generations. We analyzed mean telomere length and MDM2-SNP309 polymorphism status in individuals from multiple LFS families and controls. A total of 45 peripheral blood lymphocyte samples were analyzed from 9 LFS families and 15 controls. High rate of MDM2-SNP309 was found in TP53 carriers (P = 0.0003). In children, telomere length was shorter in carriers affected with cancer than in nonaffected carriers and wild-type controls (P < 0.0001). The same pattern was seen in adults (P = 0.002). Within each family, telomere length was shorter in children with cancer than in their nonaffected siblings and their noncarrier parents. Telomere attrition between children and adults was faster in carriers than in controls. Our results support the role of MDM2-SNP309 as a genetic modifier in LFS. The novel finding of accelerated telomere attrition in LFS suggests that telomere length could explain earlier age of onset in successive generations of the same family with identical TP53/MDM2-SNP309 genotypes. Furthermore, telomere shortening could predict genetic anticipation observed in LFS and may serve as the first rational biological marker for clinical monitoring of these patients.

Root conditioning in periodontology - Revisited.

OBJECTIVE: Root surfaces of periodontitis-affected teeth are hypermineralized and contaminated with cytotoxic and other biologically active substances. To achieve complete decontamination of the tooth surfaces, various methods including root conditioning following scaling and root planning are present. The main objective of this article is to throw light on the different root conditioning agents used and the goals accomplished by root conditioning in the field of periodontology. MATERIALS AND METHODS: 20 human maxillary anterior teeth indicated for extraction due to chronic periodontitis were collected and root planned. The teeth were sectioned and specimens were divided into two groups - Group I and II. Group I dentin specimens were treated with EDTA and group II specimens were treated with tetracycline HCl solution at concentration of 10% by active burnishing technique for 3 minutes. The root surface samples were then examined by scanning electron microscope (SEM). RESULTS: The results of the study showed that EDTA and tetracycline HCl were equally effective in removing the smear layer. It was observed that the total and patent dentinal tubules were more in number in teeth treated with tetracycline as compared to EDTA group. However, EDTA was found to be much more effective as root conditioning agent because it enlarged the diameter of dentinal tubules more than that of tetracycline HCl. CONCLUSION: Results of in-vitro study showed that both the agents are good root conditioning agents if applied in addition to periodontal therapy. However, further studies are required to establish the in-vivo importance of EDTA and tetracycline HCL as root conditioners.

Comparison of the effect of different medicaments on surface reproduction of two commercially available Polyvinyl Siloxane impression materials - An Invitro Study.

OBJECTIVE: To determine the effect of different retraction cord medicaments on surface detail reproduction of polyvinyl siloxane impression materials and compare this effect on any two brands of commercially available polyvinyl siloxane impression materials. MATERIAL AND METHODS: Four stainless steel dies were made according to ADA specification no.19. Three dies were treated with aluminium chloride (5%), ferric sulphate (13.3%) and epinephrine (0.1%) while the fourth one was left untreated to serve as control. Two impression materials (Dentsply and 3M ESPE) were used. RESULTS: All the three medicaments adversely affected the surface detail reproduction of both the brands of the polyvinyl siloxane impression materials. These effects were statistically significant as compared to untreated control. The impressions of 3M ESPE brand have shown better surface detail reproduction as compared to Dentsply impression material. CONCLUSION: Surface detail reproduction of the polyvinyl siloxane impression materials is adversely affected by the retraction cord medicaments. The presence of moisture or any traces of the medicaments should be removed from the tooth surface to provide a dry field for the correct reproduction of the surface detail of these materials. Key words:Polyvinyl Siloxane, retraction cord medicaments, surface detail reproduction.