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Publications (85)728.59 Total impact
Article: Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer.[Show abstract] [Hide abstract]
ABSTRACT: Purpose:To analyse the effect of germline mutations in BRCA1 and BRCA2 on mortality in ovarian cancer patients up to ten years after diagnosis. Experimental Design:We used unpublished survival time data for 2,242 patients from two case-control studies and extended survival-time data for 4,314 patients from previously reported studies. All participants had been screened for deleterious germline mutations in BRCA1 and BRCA2. Survival time was analysed for the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as time-varying covariates. Competing risks were analysed using Fine and Gray model. Results: The combined 10-year overall survival was 30% (95% CI, 28%-31%) for non-carriers, 25% (95% CI, 22%-28%) for BRCA1 carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The hazard ratio for BRCA1 was 0.53 at time zero and increased over time becoming greater than one at 4.8 years. For BRCA2, the hazard ratio was 0.42 at time zero and increased over time (predicted to become greater than one at 10.5 years). The results were similar when restricted to 3,202 patients with high-grade serous tumors, and to ovarian cancer specific mortality. Conclusions: BRCA1/2 mutations are associated with better short-term survival, but this advantage decreases over time and, in BRCA1 carriers is eventually reversed. This may have important implications for therapy of both primary and relapsed disease and for analysis of long-term survival in clinical trials of new agents, particularly those that are effective in BRCA1/2 mutation carriers.Clinical cancer research : an official journal of the American Association for Cancer Research. 11/2014;
- New England Journal of Medicine 10/2014; 371(17):1651-2. · 54.42 Impact Factor
Article: Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.[Show abstract] [Hide abstract]
ABSTRACT: Background: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and non-genetic modifying factors. In this study we evaluated the putative role of variants in many candidate modifier genes. Methods: Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n=3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. Results: The observed p-values of association ranged between 0.005-1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. Conclusion: There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. Impact: Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies.10/2014;
Article: Fanconi anaemia: genetics, molecular biology, and cancer - implications for clinical management in children and adults[Show abstract] [Hide abstract]
ABSTRACT: Fanconi anaemia (FA) is an inherited disease with congenital and developmental abnormalities, cross-linker hypersensitivity and extreme cancer predisposition. With better understanding of the genetic and molecular basis of the disease, and improved clinical management, FA has been transformed from a life-limiting paediatric disease to an uncommon chronic condition that needs lifelong multidisciplinary management, and a paradigm condition for the understanding of the gene-environment interaction in the aetiology of congenital anomalies, haematopoiesis and cancer development. Here we review genetic, molecular and clinical aspects of FA, and discuss current controversies and future prospects.Clinical Genetics 10/2014; · 4.25 Impact Factor
Article: Biallelic somatic SMARCA4 mutations in small cell carcinoma of the ovary, hypercalcemic type (SCCOHT)[Show abstract] [Hide abstract]
ABSTRACT: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare, aggressive tumor that primarily affects young women. SCCOHT has recently been identified as a monogenic disorder caused by germline and/or somatic SMARCA4 mutations. We describe a 15-year-old Caucasian female with a SCCOHT harboring a previously unreported somatic mutation in the SMARCA4 gene (c.1757delA; p.K586.fs) with loss of heterozygosity. No germline mutation was identified. Subsequent immunohistochemical staining confirmed loss of SMARCA4 protein. These molecular findings will aid with SCCOHT diagnosis through immunohistochemical staining for SMARCA4 and in the future may have implications for the management of this disease. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.Pediatric Blood & Cancer 10/2014; · 2.35 Impact Factor
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ABSTRACT: Germline loss-of-function mutations in PALB2 are known to confer a predisposition to breast cancer. However, the lifetime risk of breast cancer that is conferred by such mutations remains unknown.New England Journal of Medicine 08/2014; 371(6):497-506. · 54.42 Impact Factor
Article: DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.[Show abstract] [Hide abstract]
ABSTRACT: Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7×10-3) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8×10-3). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.PLoS Genetics 04/2014; 10(4):e1004256. · 8.52 Impact Factor
Article: Germline and somatic SMARCA4 mutations characterize small cell carcinoma of the ovary, hypercalcemic type.[Show abstract] [Hide abstract]
ABSTRACT: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is the most common undifferentiated ovarian malignancy in women under 40 years of age. We sequenced the exomes of six individuals from three families with SCCOHT. After discovering segregating deleterious germline mutations in SMARCA4 in all three families, we tested DNA from a fourth affected family, which also carried a segregating SMARCA4 germline mutation. All the familial tumors sequenced harbored either a somatic mutation or loss of the wild-type allele. Immunohistochemical analysis of these cases and additional familial and non-familial cases showed loss of SMARCA4 (BRG1) protein in 38 of 40 tumors overall. Sequencing of cases with available DNA identified at least one germline or somatic deleterious SMARCA4 mutation in 30 of 32 cases. Additionally, the SCCOHT cell line BIN-67 had biallelic deleterious mutations in SMARCA4. Our findings identify alterations in SMARCA4 as the major cause of SCCOHT, which could lead to improvements in genetic counseling and new treatment approaches.Nature Genetics 03/2014; · 35.21 Impact Factor
Article: Lymphocyte telomere length is longer in BRCA1 and BRCA2 mutation carriers but does not affect subsequent cancer risk.[Show abstract] [Hide abstract]
ABSTRACT: Background:Telomere length has been linked to risk of common diseases, including cancer, and has previously been proposed as a biomarker for cancer risk. Germline BRCA1 and BRCA2 mutations predispose to breast, ovarian and other cancer types. Methods:We investigated telomere length in BRCA mutation carriers and their non-carrier relatives and further examined whether telomere length is a modifier of cancer risk in mutation carriers. We measured mean telomere length in DNA extracted from whole blood using high-throughput Q-PCR. Participants were from the EMBRACE study in the UK and Eire (n=4,822) and comprised BRCA1 (n=1,628) and BRCA2 (n=1,506) mutation carriers and their non-carrier relatives (n=1,688). Results:We find no significant evidence that mean telomere length is associated with breast or ovarian cancer risk in BRCA mutation carriers. However, we find mutation carriers to have longer mean telomere length than their non-carrier relatives (all carriers vs. non-carriers, P-trend=0.0018), particularly in families with BRCA2 mutations (BRCA2 mutation carriers vs. all non-carriers, P-trend=0.0016). Conclusions:Our main and unexpected finding is that BRCA mutation carriers (regardless of cancer status) have longer telomeres than their non-mutation carrier, non-cancer-affected relatives. The longer telomere length in BRCA2 mutation carriers is consistent with its role in DNA damage response. Overall, it appears that increased telomere length may be a consequence of these mutations, but is not itself directly related to the increased cancer risk in carriers. Impact:Our findings lend little support to the hypothesis that short mean telomere length predisposes to cancer.Cancer Epidemiology Biomarkers & Prevention 03/2014; · 4.56 Impact Factor
Article: Prospective cohort study assessing outcomes of patients from families fulfilling criteria for hereditary diffuse gastric cancer undergoing endoscopic surveillance.[Show abstract] [Hide abstract]
ABSTRACT: Prophylactic total gastrectomy is performed in hereditary diffuse gastric cancer (HDGC) patients carrying the CDH1 mutation because endoscopic surveillance often fails to detect microscopic disease. The aim of this study was to determine the natural history and outcomes of patients with HDGC undergoing endoscopy. Prospective, cohort observational study. Tertiary referral center. Patients fulfilling criteria for HDGC who opted to undergo endoscopy. Research surveillance program using high-resolution white-light endoscopy with autofluorescence and narrow-band imaging combined with targeted and multiple random biopsies assessed by an expert histopathologist for the presence of signet ring cell carcinoma. The primary endpoint was the endoscopic yield of microscopic signet ring cell carcinoma according to patient mutation status and subsequent decision to undergo surgery. The secondary endpoint was the additional yield of targeted biopsies compared with random biopsies. Between September 2007 and March 2013, 29 patients from 17 families underwent 70 surveillance endoscopies. Signet ring cell carcinoma foci were identified in 14 of 22 (63.6%) patients with confirmed CDH1 germline mutations and 2 of 7 (28.6%) with no pathogenic mutation identified. Eleven of 16 (9 CDH1-positive) patients proceeded to gastrectomy in a median 5.7 months. Five patients delayed surgery. In 1 patient, advanced gastric cancer developed 40.2 months after the first endoscopic findings. No control group. Careful white-light examination with targeted and random biopsies combined with detailed histopathology can identify early lesions and help to inform decision making with regard to gastrectomy. Autofluorescence and narrow-band imaging are of limited utility. Delaying gastrectomy in individuals with signet ring cell carcinoma foci carries a high risk and has to be weighed carefully.Gastrointestinal endoscopy 01/2014; · 6.71 Impact Factor
Article: Targeted Prostate Cancer Screening in BRCA1 and BRCA2 Mutation Carriers: Results from the Initial Screening Round of the IMPACT Study.[Show abstract] [Hide abstract]
ABSTRACT: Men with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) is an international consortium of 62 centres in 20 countries evaluating the use of targeted PCa screening in men with BRCA1/2 mutations. To report the first year's screening results for all men at enrolment in the study. We recruited men aged 40-69 yr with germline BRCA1/2 mutations and a control group of men who have tested negative for a pathogenic BRCA1 or BRCA2 mutation known to be present in their families. All men underwent prostate-specific antigen (PSA) testing at enrolment, and those men with PSA >3 ng/ml were offered prostate biopsy. PSA levels, PCa incidence, and tumour characteristics were evaluated. The Fisher exact test was used to compare the number of PCa cases among groups and the differences among disease types. We recruited 2481 men (791 BRCA1 carriers, 531 BRCA1 controls; 731 BRCA2 carriers, 428 BRCA2 controls). A total of 199 men (8%) presented with PSA >3.0 ng/ml, 162 biopsies were performed, and 59 PCas were diagnosed (18 BRCA1 carriers, 10 BRCA1 controls; 24 BRCA2 carriers, 7 BRCA2 controls); 66% of the tumours were classified as intermediate- or high-risk disease. The positive predictive value (PPV) for biopsy using a PSA threshold of 3.0 ng/ml in BRCA2 mutation carriers was 48%-double the PPV reported in population screening studies. A significant difference in detecting intermediate- or high-risk disease was observed in BRCA2 carriers. Ninety-five percent of the men were white, thus the results cannot be generalised to all ethnic groups. The IMPACT screening network will be useful for targeted PCa screening studies in men with germline genetic risk variants as they are discovered. These preliminary results support the use of targeted PSA screening based on BRCA genotype and show that this screening yields a high proportion of aggressive disease. In this report, we demonstrate that germline genetic markers can be used to identify men at higher risk of prostate cancer. Targeting screening at these men resulted in the identification of tumours that were more likely to require treatment.European Urology 01/2014; · 10.48 Impact Factor
Article: Mutation analysis of PALB2 in BRCA1 and BRCA2-negative breast and/or ovarian cancer families from Eastern Ontario, Canada.[Show abstract] [Hide abstract]
ABSTRACT: PALB2 has emerged as a breast cancer susceptibility gene. Mutations in PALB2 have been identified in almost all breast cancer populations studied to date, but the rarity of these mutations and lack of information regarding their penetrance makes genetic counseling for these families challenging. We studied BRCA1/2 -negative breast and/or ovarian cancer families to a) assess the contribution of PALB2 mutations in this series and b) identify clinical, pathological and family history characteristics that might make PALB2 screening more efficient.Hereditary Cancer in Clinical Practice 01/2014; 12(1):19. · 1.71 Impact Factor
Article: Fanconi anaemia, BRCA2 mutations and childhood cancer: a developmental perspective from clinical and epidemiological observations with implications for genetic counselling.[Show abstract] [Hide abstract]
ABSTRACT: Fanconi anaemia (FA) is an inherited condition characterised by congenital and developmental abnormalities and a strong cancer predisposition. In around 3-5% of cases FA is caused by biallelic mutations in the BRCA2 gene. Individuals heterozygous for BRCA2 mutations have an increased risk of inherited breast and ovarian cancer. We reviewed the mutation spectrum in BRCA2-associated FA, and the spectrum and frequency of BRCA2 mutations in distinct populations. The rarity of FA due to biallelic BRCA2 mutations supports a fundamental role of BRCA2 for prevention of malignant transformation during development. The spectrum of malignancies seen associated with FA support the concept of a tissue selectivity of BRCA2 mutations for development of FA-associated cancers. This specificity is illustrated by the distinct FA-associated BRCA2 mutations that appear to predispose to specific brain or haematological malignancies. For some populations, the number of FA-patients with biallelic BRCA2 disruption is smaller than that expected from the carrier frequency, and this implies that some pregnancies with biallelic BRCA2 mutations do not go to term. The apparent discrepancy between expected and observed incidence of BRCA2 mutation-associated FA in high-frequency carrier populations has important implications for the genetic counselling of couples with recurrent miscarriages from high-risk populations.Journal of Medical Genetics 11/2013; · 5.70 Impact Factor
Article: Hi-Plex for high-throughput mutation screening: application to the breast cancer susceptibility gene PALB2.[Show abstract] [Hide abstract]
ABSTRACT: Massively parallel sequencing (MPS) has revolutionised biomedical research and offers enormous capacity for clinical application. We previously reported Hi-Plex, a streamlined highly-multiplexed PCR-MPS approach, allowing a given library to be sequenced with both the Ion Torrent and TruSeq chemistries. Comparable sequencing efficiency was achieved using material derived from lymphoblastoid cell lines and formalin-fixed paraffin-embedded tumour. Here, we report high-throughput application of Hi-Plex by performing blinded mutation screening of the coding regions of the breast cancer susceptibility gene PALB2 on a set of 95 blood-derived DNA samples that had previously been screened using Sanger sequencing and high-resolution melting curve analysis (n = 90), or genotyped by Taqman probe-based assays (n = 5). Hi-Plex libraries were prepared simultaneously using relatively inexpensive, readily available reagents in a simple half-day protocol followed by MPS on a single MiSeq run. We observed that 99.93% of amplicons were represented at >=10X coverage. All 56 previously identified variant calls were detected and no false positive calls were assigned. Four additional variant calls were made and confirmed upon re-analysis of previous data or subsequent Sanger sequencing. These results support Hi-Plex as a powerful approach for rapid, cost-effective and accurate high-throughput mutation screening. They further demonstrate that Hi-Plex methods are suitable for and can meet the demands of high-throughput genetic testing in research and clinical settings.BMC Medical Genomics 11/2013; 6(1):48. · 3.91 Impact Factor
Article: Familial Rhabdoid Tumour "Avant La Lettre" - from pathology review to exome sequencing and back again.[Show abstract] [Hide abstract]
ABSTRACT: Here we provide compelling evidence that Next Generation Sequencing will revolutionise diagnostics. We reappraised a case from 1991, published in 1993, describing the unique occurrence of an ovarian immature teratoma arising in a young woman and a clonally distinct intracerebral immature teratoma developing in her daughter. We conducted whole exome sequencing on constitutional DNA from the mother and her daughter and identified a previously unreported nonsense mutation (c.3533G>A; p.Trp1178*) in the chromatin remodelling gene, SMARCA4, that was present in both individuals and was subject to nonsense-mediated decay. Tumour analysis by Sanger sequencing revealed a somatic SMARCA4 mutation, both in the mother (c.2438+1G>T), and in her daughter (c.3229C>T; p.Arg1077*), which are predicted to be truncating. As immature teratomas are classified as germ cell tumours, we performed a comprehensive mutation survey of 106 apparently sporadic germ cell tumours but did not find any other clearly deleterious SMARCA4 mutations. Recently, inactivating mutations in SMARCA4 have been found in two cases of rhabdoid tumour predisposition syndrome type 2. In the light of these findings, renewed efforts to locate previously unobtainable tumour samples were successfully undertaken. Histopathological and immunohistochemical re-analysis of the daughter's tumour revealed that it was indeed a rhabdoid tumour (atypical teratoid/rhabdoid tumour). In this context, the original pathology report of the mother's ovarian tumour was re-interpreted as describing a malignant rhabdoid tumour of the ovary. This report raises the question as to whether molecular genetic analysis should be included in tumour classification, alongside more traditional microscopy-based methods. The use of new sequencing technologies, particularly when applied to archived samples, will lead to many more "molecular re-diagnoses". This is the earliest known case of rhabdoid tumour predisposition syndrome type 2 and the only described case with an autosomal dominant pattern of inheritance, only discovered through an exome sequencing project.The Journal of Pathology 06/2013; · 7.59 Impact Factor
Article: Germline BRCA Mutations Are Associated With Higher Risk of Nodal Involvement, Distant Metastasis, and Poor Survival Outcomes in Prostate Cancer.[Show abstract] [Hide abstract]
ABSTRACT: PURPOSETo analyze the baseline clinicopathologic characteristics of prostate tumors with germline BRCA1 and BRCA2 (BRCA1/2) mutations and the prognostic value of those mutations on prostate cancer (PCa) outcomes. PATIENTS AND METHODS This study analyzed the tumor features and outcomes of 2,019 patients with PCa (18 BRCA1 carriers, 61 BRCA2 carriers, and 1,940 noncarriers). The Kaplan-Meier method and Cox regression analysis were used to evaluate the associations between BRCA1/2 status and other PCa prognostic factors with overall survival (OS), cause-specific OS (CSS), CSS in localized PCa (CSS_M0), metastasis-free survival (MFS), and CSS from metastasis (CSS_M1).ResultsPCa with germline BRCA1/2 mutations were more frequently associated with Gleason ≥ 8 (P = .00003), T3/T4 stage (P = .003), nodal involvement (P = .00005), and metastases at diagnosis (P = .005) than PCa in noncarriers. CSS was significantly longer in noncarriers than in carriers (15.7 v 8.6 years, multivariable analyses [MVA] P = .015; hazard ratio [HR] = 1.8). For localized PCa, 5-year CSS and MFS were significantly higher in noncarriers (96% v 82%; MVA P = .01; HR = 2.6%; and 93% v 77%; MVA P = .009; HR = 2.7, respectively). Subgroup analyses confirmed the poor outcomes in BRCA2 patients, whereas the role of BRCA1 was not well defined due to the limited size and follow-up in this subgroup. CONCLUSION Our results confirm that BRCA1/2 mutations confer a more aggressive PCa phenotype with a higher probability of nodal involvement and distant metastasis. BRCA mutations are associated with poor survival outcomes and this should be considered for tailoring clinical management of these patients.Journal of Clinical Oncology 04/2013; · 18.04 Impact Factor
Article: Germ-line DICER1 mutations do not make a major contribution to the etiology of familial testicular germ cell tumours.[Show abstract] [Hide abstract]
ABSTRACT: BACKGROUND: The RNase III enzyme DICER1 plays a central role in maturation of microRNAs. Identification of neoplasia-associated germ-line and somatic mutations in DICER1 indicates that mis-expression of miRNAs in cancer may result from defects in their processing. As part of a recent study of DICER1 RNase III domains in 96 testicular germ cell tumors, a single RNase IIIb domain mutation was identified in a seminoma. To further explore the importance of DICER1 mutations in the etiology of testicular germ cell tumors (TGCT), we studied germ-line DNA samples from 43 probands diagnosed with familial TGCT. FINDINGS: We carried out High Resolution Melting Curve Analysis of DICER1 exons 2--12, 14--19, 21 and 24--27. All questionable melt curves were subjected to confirmatory Sanger sequencing.Sanger sequencing was used for exons 13, 20, 22 and 23. Intron-exon boundaries were included in all analyses. We identified 12 previously reported single nucleotide polymorphisms and two novel single nucleotide variants. No likely deleterious variants were identified; notably no mutations that were predicted to truncate the protein were identified. CONCLUSIONS: Taken together with previous studies, the findings reported here suggest a very limited role for either germ-line or somatic DICER1 mutations in the etiology of TGCT.BMC Research Notes 04/2013; 6(1):127.
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ABSTRACT: Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10(-8)). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer.PLoS Genetics 03/2013; 9(3):e1003173. · 8.52 Impact Factor
Article: Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk.[Show abstract] [Hide abstract]
ABSTRACT: BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2×10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers.PLoS Genetics 03/2013; 9(3):e1003212. · 8.52 Impact Factor
Article: Heterozygous mutations in the PALB2 hereditary breast cancer predisposition gene impact on the three-dimensional nuclear organization of patient-derived cell lines.[Show abstract] [Hide abstract]
ABSTRACT: PALB2/FANCN is a BRCA1- and BRCA2-interacting Fanconi Anemia (FA) protein crucial for key BRCA2 genome caretaker functions. Heterozygous germline mutations in PALB2 predispose to breast cancer and biallelic mutations cause FA. FA proteins play a critical role in the telomere maintenance pathway, with telomeric shortening observed in FA cells. Less is known about telomere maintenance in the heterozygous state. Here, we investigate the roles of PALB2 heterozygous mutations in genomic instability, an important carcinogenesis precursor. Patient-derived lymphoblastoid (LCL) and fibroblast (FCL) cell lines with monoallelic truncating PALB2 mutations were investigated using a combination of molecular imaging techniques including centromeric FISH, telomeric Q-FISH and spectral karyotyping (SKY). Mitomycin C and Cisplatin sensitivity was assayed via cellular metabolism of WST-1. The PALB2 c.229delT FCL showed increases in telomere counts associated with increased mean intensity compared with two wild-type FCLs generated from first-degree relatives (P =1.04E-10 and P =9.68E-15) and it showed evidence of chromosomal rearrangements. Significant differences in centromere distribution were observed in one of three PALB2 heterozygous FCLs analyzed when compared with PALB2 wild-type, BRCA1 and BRCA2 heterozygous FCLs. No significant consistently increased sensitivity to Mitomycin C or Cisplatin was observed in LCLs. Our results are suggestive of an altered centromere distribution profile and a telomere instability phenotype. Together, these may indicate critical nuclear organization defects associated with the predisposition to transformation and early stage development of PALB2-related cancers. © 2013 Wiley Periodicals, Inc.Genes Chromosomes and Cancer 01/2013; · 3.55 Impact Factor
Top Journals
University of Cambridge
Cambridge, England, United Kingdom
- Department of Medical Genetics
University of ManitobaWinnipeg, Manitoba, Canada
McGill University
Montréal, Quebec, Canada
- • Department of Human Genetics
- • Department of Oncology
- • Sir Mortimer B. Davis Jewish General Hospital
Université de Montréal
Montréal, Quebec, Canada
- Department of Radiology, Radiation Oncology and Nuclear Medicine
Centre hospitalier de l'Université de Montréal (CHUM)
Montréal, Quebec, Canada
- Département Médecine dentaire
Memorial Sloan-Kettering Cancer Center
New York City, NY, United States
- Department of Medicine
Jewish General HospitalMontréal, Quebec, Canada
Institute for Child Health Policy (ICHP)North East, Pennsylvania, United States
King's College London
London, ENG, United Kingdom
- Department of Medical and Molecular Genetics


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New answers tagged reading
I found this interesting. but only reading is not enough you also need to grab ideas from what you read. this may help you, and by clicking on these and reading these article means you are trying to read. So your journey begin from here with hopefully good starting points.
Just don't read them. Or, imagine what's next if you just let it go. Is it really that bad? Well, since you've posted a question here, I guess it is. So get deeper into why is it important for you to read programming books, or what will you miss if you don't. Two more helpful things to think about is to have some kind of a motivational kick before drifting ...
I partly switched to podcasts. I listen them in the train, while running, ... And when I hear an interesting thing I'm searching the internet. Normally the texts there are shorter and not that timeconsuming. It's not like reading a good book, but it's better than nothing.
I'll try to contribute by throwing some ideas around. I think reading (or better said, learning) is a way of life, which one I do not fully master all of the time, but at least seem to be quite comfortable with some of the time. I hope it helps you. First, ask yourself why you are reading programming books in the first place. If you want to become a better ...
There are only a couple of programming books I've read cover to cover: Code Complete and The Pragmatic Programmer. Any other programming book I've read has been with the purpose to extract enough information to get a job done. It's a question of utility. Reading a short story is usually a different matter. You're drawn into the world the author created. ...
From experience, opening a new programming book is always exciting. I start reading (even the dedication, acknowledgements etc.), but gradually loose the vibe and get tired. Here are a few concepts that help me carry on: Divide and Conquer - in programming (and GTD), D&C is dividing a complex task into simpler ones that can be more easily tackled. Plan ...
Top 50 recent answers are included

subset: commoncrawl


text:
W&T Offshore
MCC Transport's New Weekly Indonesia to Japan Service
MCC Transport launched of a new weekly Indonesia - Japan Service (TS4) that links the ports of Indonesia directly with those in Japan, Taiwan and South China. The TS4 service goes on a 28 days rotation, covering the following ports: Tokyo (Japan), Yokohama (Japan), Nagoya (Japan), Osaka (Japan), Kobe (Japan), Keelung (Taiwan), Taichung (Taiwan), Kaohsiung (Taiwan), Hong Kong (China), Shekou (China), Jakarta (Indonesia), Surabaya (Indonesia), Shekou (China), Hong Kong (China), Xiamen (China) and Tokyo (Japan). The first sailing will be on the TS Nagoya, which is scheduled to depart Tokyo on 23 June 2010. www.mcc.com.sg
This Day in U.S. Naval History – November 10
1775 - Congress votes to raise two battalions of Continental Marines, establishing the Marine Corps. 1941 - U.S. escorted convoy WS 12, carrying 20,000 British troops to Singapore, sails from Halifax (Source: Navy News Service)
Gulf Tanker Rates Fall
Crude tanker rates from the Arabian Gulf to Asia on 2mn-barrel tankers fell to its lowest in more than six weeks as the ships available at the end of August outnumber cargoes, according to a Bloomberg report. In less than a month freight rates for VLCCs reportedly have dropped 40 percent as charterers held back from hiring vessels, allowing a surplus to build up. GS Caltex Corp, South Korea's second-largest oil refiner, booked a VLCC, Hebei Mountain to load crude on August 23 at WS 62
Oil Freight Charges To Go Higher?
Bloated oil freight charges could surge yet higher this year, adding to the already inflated cost of world oil imports, shippers said. Tanker brokers are predicting a mid-November stampede to ship crude from the Middle East, pushing charter rates to new peaks amid a perceived shortage of quality vessels. In January, very large crude carriers (VLCCs) sailing from the Gulf to Japan were fetching a price of worldscale 49, equivalent to 75 cents a barrel
Cargotec Appoints Svennevig as VP
Cargotec appoints Tom Svennevig Vice President for MacGregor advanced load-handling business. Cargotec has appointed Tom Svennevig as Vice President responsible for the company's advanced load-handling business line as of 24 October 2011. Mr Svennevig is experienced in the offshore business, and he joins Cargotec from Aker Pusnes in Norway where he was Vice President, Deck Machinery. Mr Svennevig is based in Kristiansand, Norway
ISS Wins Gas Pipeline Logistics Contract
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McKenna Long & Aldridge LLP (MLA) is an international law firm with more than 575 attorneys and public policy advisors in 13 offices and 11 markets. The firm is uniquely positioned at the intersection of law, business and government, representing clients in the areas of complex litigation, corporate, energy, environment, family wealth, finance, government contracts, health care, infrastructure, insurance, intellectual property, public policy, real estate, and technology.
Hobie Alter dies at 80: LA Times obituary
Bora Bora owners charged with tax evasion
Skateboardermag.com: Norb Garrett's video obit for Skateboarder in print and online
YoungEntrepreneur.com: Aaron Levant
Ad Age: Bonnier sells Ski, Skiing and Skiing Business magazines, Warren Miller Entertainment
Sports Goggles Provide Data and Distraction
Inc. Magazine: "The Way I Work: Yvon Choinard"
OC Weekly: Profile of Pelle Klein, founder of skate startup Costa Misery
Forbes: Profile of Nick Woodman, the "Mad Billionaire behind Go-Pro, the world's hottest camera company"
Being an Executive Edition member allows me to not miss a beat when it comes to the Industry business news. Definitely keeps me in the loop plus goes great with my morning joe.- By Tony Perez, Surfer and Surfing magazines
"Shop-Eat-Surf" is now officially, the first stop in the morning for industry news. Accurate reporting, no sensationalism, and just the facts. Refreshing support to an incredible industry with a very bright future. Tiffany has cemented her role in the industry....the site is thought provoking, and inspirational. Learning the stories of others is incredibly useful. Great way to connect the retail community with the wholesale and financial, instantly and nationwide. ... And the Executive Edition rules.- By Bob Hurley, Chairman, Hurley International
MOSS ADAMS: Webinar 12/2 on internal controls to increase the value of your business.
AGENDA: 12/30 deadline to pre-register for Jan. 5-6 Long Beach show.
CIT TRADE FINANCE: Middle-market retailers cautiously optimistic for holiday.
Details on Industry Insight.
Press Release:
Vans and DQM followed up Thursday's big opening day and private event at the new Vans DQM General store in NYC with a larger party for the community on Friday, September 16 at the House of Vans in Brooklyn featuring food, drink and a performance by Suicidal Tendencies.
Bringing ST out from Venice capped off a special week that saw the Vans & DQM crews put in long hours in final prep for business. Mike Muir and company didn't disappoint playing for nearly 90 minutes and inviting the moshers up on stage to close out the set.
Check out photographer Bryan Derballa's images that capture the night's energy.
Special thanks to Brooklyn Brewery and Vita Coco for drinks and the amazing food from the Korilla BBQ truck and the LES' Meatball Shop.
Located at 93 Grand, the Vans DQM General is Vans' first store in Manhattan and the co-branded project with local skate and streetwear purveyor DQM is the first of a kind in the United States for Vans. Expect to find the newest cut & sew and accessories from DQM, the latest from Vans across several lines including our Classics, California, Surf, OTW, Skate and Vault collections and a nice selection of boards, wheels and trucks – all in a setting that beautifully nods to SOHO's unique heritage and personality.
Follow the Vans DQM General on Twitter @vansdqm and at facebook.com/vansdqm.


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CNET breaks out the most important things to know when shopping for a new television.
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The Acer Aspire Switch 10 is a budget hybrid that skips the more-common fold-back or button-clasp hinges and instead attaches its screen via a magnetic connection. It shares the same hardware limitations as other small hybrids, but can be easier to use.
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Robin Lopez had successful knee surgery
Aug 5, 2012, 9:00 AM EST
Really, New Orleans' luck had been going too well.
They draft Austin Rivers, he has surgery. They trade for Robin Lopez, now he has knee surgery. It's fine, it's just not the kind of thing you want right off the bat as the rebuilding project gets underway. From the team's presser:
The New Orleans Hornets announced today that center Robin Lopez underwent successful surgery to correct a tear of his medial meniscus in his left knee.
Lopez was acquired July 27 along with forward Hakim Warrick and cash considerations from the Phoenix Suns. The 7'0'' center averaged 5.4 points and 3.3 rebounds for the Suns last season in 14.0 minutes over 64 games.
The procedure was performed by Dr. El Attrache at the Kerlan Jobe Clinic in Los Angeles. Lopez is expected to make a full recovery and be ready for training camp this fall.
So not just arthroscopic, but a tear, albeit in the meniscus. Great. Fantastic.
Lopez has had a rash of injuries in his young career, and that's not a great sign. But these things happen, and he's expected to recover. But bear in mind he's got two months to get healthy from surgery. Not ideal.
But the Hornets were prepared to go smallball regardless, for if they hadn't pulled off the trade for Lopez, they would have had only Jason Smith as a reliable center. The surgery went well and Lopez can likely recover with no ill effects. It's just a concern for the knife to be necessary so soon after the Hornets' acquisition of him.
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Progressive Insurance
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23 March In Pakistan History
About the author
Related Posts
42 Comments
so informative….!!!!
i like this day very much.
it is so nice.i like this day very much.
it is very nice mind of vew.
i love u pakistan <3
nice speech and [I REALLY LOVE PAKISTAN]
♥ ♥ ♥ ♥ ♥ ♥ ♥ ♥ ♥ ♥ ♥ ♥ ♥ ♥ ♥ ♥ ♥
koi btaskta ha k ye copy q nhi ho raha????
Love u MUHAMMAD ALI JINNAH(THE GREATEST LEADER OF HISTORY N PAK'S HERO)SALUTE U……N THNX ALOT FOR THIS LOVELY GIFT U HAVE GIVEN US THNX THNX ALOT
I love pakistan.
i love my notion and our national hero quaid e azam
i lovwe my notion
quaide was our hero!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
nice mam/sir
speech is vry intresting so we should learn it.
so nice and informative.we should have to pray for pakistan that allah gave us a leader like muhammad ali jinnah and allama iqbal
rememberable day for pak
A nice day for me and muslim
It did helped me to write a speach for my daughter with good detail. thanx
it helped me out for my speech … thank you
i love pakistan and it's history so much…
u r ryt….
i agree with you. (pyari pari)
we should do something for poor people which sleep on roads we have to give them homes clothes
if we look aroad we are all muslims
hmmm we shOuld spend Our sOme mOny fOr pOor peOple.
and we shOuld respect poor people because they have many tentions they have many probs
ilove pakistan but if people
get love between them ,but what jinnha have making
for pakistan and look know what pakistan have did
we can get information from it
why pakistan was demanded could'nt we adjust with hindus
literature is very informative but history description is less.
this is proud for pakistan to know such history i am proud to b a pakistani
I love this all Pakistani history but sad thing is most of the Pakistani people's are going on a wrong path now a days.
it is great knowlege 4 us.
what u say,about the history of pakistan..???
it is very great knowlege for us
Thanx were payable to Allah and it is payable for providing the such leadership who gave pakistan ,
its so great knowledge of history
really nice sir
really nice
but unfortunate majority pakistani forgot their promise.We have justice in our mind and in our voice,also we have guts to raise our voice against injustice… but not guts to change.
Very nice sir


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Protester shot during Cairo sit-in may have been targeted
CAIRO — Gunmen drove into Cairo's Tahrir Square before dawn on Monday and fired at an anti-government sit-in, seriously wounding a protester who had been jailed and tortured by former military rulers after he witnessed the killing of another activist. Two lawyers involved in the case suggested it was a targeted attack.
Lawyer Tamer Gomaa identified the seriously wounded activist as Muhanad Samir, 19, and said he was battling for his life with a number of pellets embedded in his skull and in his face.
Gomaa said witnesses recognized the attackers and identified them as security agents dressed in civilian clothes. Gomaa quoted witnesses as saying some of the attackers had visited the square hours before and inquired about Samir by name and about others at the sit-in.
A security official dismissed the charges as nonsense, noting that some of the witnesses said the attackers were masked.
Other witnesses said the attacker aimed at Samir, shooting him at close range, according to Gomaa. One of the attackers was collecting bullet shells, apparently to clear evidence.
Political tensions have been running high in Egypt over the past month pitting opponents of Islamist President Mohamed Morsy against his supporters, turning violent at times.
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Dual Fuel Systems, at what point do they make sense?
Heat Pump with furnace backup. These make no sense in our area with local NG rates, but they do…See More
Hi. I would like to participate in the development/refinement of the pattern language. Please advise.
© 2014 Created by Lawrence Berkeley National Laboratory.


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MainStay Suites
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107 Brentwood Blvd , Brentwood, TN, US, 37027
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The Vanderbilt Commodores represent the athletic programs and teams of Vanderbilt University in Nashville, Tennessee. The school maintains Division I standing as a member of the Southeastern Conference, and is also an active member of the American Lacrosse Conference. Since the debut of its athletics program in 1886, Vanderbilt University has grown to become one of the most recognizable names in intercollegiate sports. In addition to the school's success across several varsity sports, the women's bowling team became the first in Vanderbilt University's history to win a team NCAA Championship.View More >
Tin Roof RevivalTin RoofNovember 25, 2014 8:00 PM
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Some of Nashvilles greatest musicians and up and coming somgwriters get together and jam out at the roof every Tuesday starting at 8pm! Join us for what is shaping up to be Nashville's hottest Writers Round.View More >
Artist lineup announced via Twitter every week! Follow us here!
Artist lineup announced via Twitter every week! Follow us here!
Lucinda WilliamsCity WineryNovember 25, 2014 8:00 PM
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Lucinda Williams is an Americana/alternative country singer/songwriter who rose to national prominence with the release of her universally-acclaimed self-titled third album in 1988. Williams began her ascent to music stardom by tirelessly recording music in a traditional country and blues style since 1978, despite never truly receiving much attention for her efforts. However, following the release of an eponymous album in 1988, Williams would not only receive the national attention she deserved, but a track off the album, "Passionate Kisses," was covered and recorded by Mary Chapin Carpenter in 1994, earning Williams a songwriting Grammy that year for "Best Country Song." Since then, Williams has managed to maintain a successful career as a singer/songwriter and was even named "America's Best Songwriter" by Time magazine in 2002.View More >
Two Fresh @ Anthem In Nashville, TnAnthemNovember 25, 2014 7:00 PM
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Two Fresh is a hip-hop/electronica duo from Asheville, North Carolina that was formed into a professional act in 2008 by fraternal twins Sherwyn and Kendrick Nicholls. Since adding a third member that year to man the drums, the Nicholls brothers have been making tremendous waves in the world of underground hip-hop, particularly throughout the southeast US. Two Fresh's debut album The Baker's Dozen was hailed by critics as an ingenious mixture of a variety of unique musical elements into a hip-hop tinged electronica brew, leaving many to wonder where these freshly minted golden twins of hip-hop will end up next.View More >
Earn valuable points toward free nights.


text:
I have come to understand that language shapes the way people think and feel, and vice versa. I often felt that I could not describe in English what I was feeling. I could not find in English exact expressions matching my bodily sensations.Kyung-Joo Yoon, Canberra, 2007
A busy street. An unfamiliar country. You're lost. All you can hear is a language you can't understand. Suddenly you hear words or an accent you recognise. Immediately you feel more at home.
Often we take our own language and accent for granted. Yet our words connect us to so many parts of identity — our family, literature, humour, even our dreams. What language do you dream in?
Language and accents also separate us. Some people hear a conversation in a public place that's not in English, and feel threatened.
Are they talking about me? Why don't they speak English?
If we lose our language we lose a part of ourselves.
Meet Carlos and hear his story.
Download the Carlos - language video
Watch this video with a transcript
I respect others by respecting all race and religions
Hi Michael. I was wondering where you got the information about Robert Parry being a seaman on the Eliza Caroline. I too have heard a similar story but have nev...
To read the latest tweets from @immigration_mv
Follow Immigration Museum on
I had a question about the Myer rooftop carnival during the 1960's. I was wondering whether there are any photographs available as I remember it fondly but ...


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Clomid and OI #107
Started by Forum Moderator , Dec 23 2012 06:16 PM
270 replies to this topic
Posted 23 December 2012 - 06:16 PM
New thread time ladies.
Here's the link to your old thread.
Posted 23 December 2012 - 06:56 PM
Veryclucky It's great that you are doing so well towards your weight loss goal. Hopefully you reach it soon and can start using clomid to try and get your BFP. I'm trying to lose weight as well as I am overweight but it's proving hard to shift. I will just have to increase my exercise frequency I think but I'll get there. Thank you for sharing your story too.
Jessie Awesome work on making an egg, I knew you would, I had a good feeling about it and it was just delayed. It must be something in the water as it's been good BD here too. Let's hope that continues as sometimes when TTC it just becomes a chore and that sucks.
Rosie Ooh, two eggs, fantastic! I hope one of them becomes your BFP. Hanging out to test is horrible though but at least Christmas should help to make it go a little faster with everything happening. Oh, and with my BFP I had such sore boobs from very early on. Hopefully the sore nipples are a very good sign for you!
NSG Aww, how sweet is your DB and it's great that he understands that this process can get you down sometimes. How lovely of him to get you the card. Hopefully your FS can figure out what happened and next cycle won't end so quickly. Good luck.
Fossy I take clomid CD2-6 and then O between CD14 and CD16 so 8 to 10 days for me.
Merry Christmas to everyone as I don't know that I'll be on for a few days. I hope you all have a wonderful Christmas day with friends and family.
Posted 24 December 2012 - 09:07 AM
Let us see here... I have so much to catch up on!!
jessie - HURRAH! egg on its way AND great sex - best of both worlds
Have you tested yet rosie? I demand that you pee in a cup and put a stick in it!
Veryclucky - weight loss is tough and it takes true dedication to get through it. Eventually it just becomes 'what you do'/your new lifestyle and you adjust, but those first few months are mentally and emotionally painful. So glad you are managing things well
Fossy - last cycle I o'ed 12 days after my last clomid pill. This cycle, I don't think I've O'ed - looking at my temps. BUT if I have (as FF insists), it would have been, again, 12 days after my last clomid pill.
NSG, esther, bek, Bazinga, fluffybun, Brooooookey, Mrscarlton & Lalliana - Hope everything is going all well for you ladies!
I hope I haven't left anybody out!
Quick update on my end: I'll go do my blood test today to see if I've O'ed. Hopefully will find out the results very soon after Christmas. I've just been so busy with christmas gatherings and we threw a housewarming/wedding anniversary party on Friday (was so much fun!! such a success ), life has been keeping me busy to the point where I take my temperature in the morning and forget about TTC thereafter, heh.
I don't think I've ovulated...... I'm just looking at today's and yesterday's temps, they're just, SO SO low!! FF is still saying that I have though Guess my progesterone levels shall reveal all.
Merry Christmas everybody, and be safe! Looking forward to hearing positive news from you all after the festive celebrations are over
Posted 24 December 2012 - 11:33 AM
Stuck on my phone, so it's a bit hard to toggle back to the old thread to see what's happening with everyone. Hope all is well with all of you!
Poseidon- Gopd luck for your blood test! I haven't tested yet (11DPO today), because my FS said not to until 29 December, and while I probably won't wait that long, I'm scared or ruining Christmas. My temp was down a bit this morning, so I'm feeling a bit negative about it all- not very festive! My boobs weren't sore this morning, but they are again now, and I feel heavy in my abdomen still- who knows?
To top it off, my husband's bike hasn't arrived for Christmas, and my puppy had explosive diarrhea - nothing says Christmas like a trip to the vet first thing!
Ok, going to buck up now- going to think positive!
Posted 25 December 2012 - 05:24 PM
Hope you have all had a great day ladies
Rosie my dog just got out of icu after a boute of gastro not fun at all.
Afm I forgot to call about bloods but did an way to early test yesterday and bfn
Posted 26 December 2012 - 06:47 PM
Veryclucky, I am glad your weightless journey is going well. I went to a dietician last week and she gave me a rude shock.
Lalliana, I am also overweight and that's why I have decided to do something about it. The dietician said not to have sugar for four days and that's all it takes to realise you feel so much better. But those four days will be he'll seeing as I love my soft drinks. I think I will definitely get a lot of useful tips from her. Where are you up to with anything? I am not sure what it is about this month but the best ever as you said, it becomes a chore which it has been but this month has been different
Bek_p, oh no about your dog I hope he has been resting and getting better. Let us know how you go about the results of your bloods. When can you ring up and find out?
Rosie, that's not good about your puppy I hope it's all gone and is all better crap about DH's bike it's annoying when things don't come in time mum thought that she wouldn't have anything to giv to me as we ordered Tom ford sunglasses over the net but luckily it came at Christmas Eve. Hopefully it will come in soon. Have you done a sneaky Poas?
NSG, Esther, bazinga, fluffy bun, mrscarlton and broooooky, I hope you all had a lovely Christmas and you are travelling well.
AFM, gyno sad I was making an egg and would release within three days. i still has strong strong strong opks 5 days Late? i think this is a very very strong ovulation. well anyways, about two or three days I was very nauseous, very sick and definitely not right. Christmas Eve I was not well at all and went to the walk in clinic but they were shut, I think possible hyperstimulation? Not much else is happening..... Tomorrow I am turning a quarter of a century. I really thought I would have had a baby by now, but obviously someone had other plans for me. I have my gyno appointment on 2 January, I shall see what he says. I am going to try not to Poas u til af arrives.i have told dh to hide them. But if he doesn't...... I know I am kidding myself.
I hope all of you had a lovely day. I am still recovering from it!
Edited by jessietroy, 26 December 2012 - 06:47 PM.
Posted 27 December 2012 - 04:00 AM
Tested finally, and BFN. I think I already knew- boobs haven't been nearly as sore, although no sign if AF at all...
I suppose I'll test again over the next few days if no AF, but I think this cycle is over. Gutted and going back to sleep now. Hopefully for a month!
Posted 27 December 2012 - 08:39 AM
I didn't ovulate feeling crappy dh is being super nice taking me shopping. Ill write some more later not sure if ill need to end cycle with provera or not
Posted 27 December 2012 - 08:41 AM
Sorry to hear that bek_p- today seems to suck for both of us! Shopping sounds like a nice distraction, take care of yourself! Xx
Posted 27 December 2012 - 10:17 AM
And another one for the BFN. Tested on Christmas morning because if it was + then I would have best Christmas pres ever but if was - I could have a few drinks. Oh well just have to wait for the next go around.
Posted 27 December 2012 - 10:42 AM
Rosie, bek, Esther what cd are you now bek? The BFNers, so long as AF hasn't turned up yet, there is still hope to hold onto.
AFM- did my blood test today. Nurse mutilated my arm and I feel a bruise pending (ugh!). Not sure if I Oed or not... My temp went up today, have no idea what to think. I hope I'm put out of my unknowing misery tomorrow... I tested today because I have too many HPT ICs than I know what to do with - BFN of course. Would be awkward if it was positive and I still didn't know if I Oed, heh.
Take care ladies. We're going to get through this
Edited by Poseidon768, 27 December 2012 - 10:43 AM.
Posted 27 December 2012 - 10:51 AM
Cd 27
Posted 27 December 2012 - 01:18 PM
I suppose you're right Poseidon, but I think if the test is negative at 14 days, then it is likely to stay that way. I feel really silly sitting here in tears when some people have had months of negative tests and this is my first. It just feels like it took so much to get to ovulate at all, what if it never happens again? The timing for next cycle might suck- does anyone know if you can do clomid combined with injectibles? My FS is away, but I'm going to speak to the FS covering for her tomorrow. I need to ovulate before 24 January, or there isn't any point this cycle. And if there is no point I'd really rather not take the Clomid- I ended up so depressed last time it scared me.
Posted 27 December 2012 - 02:53 PM
And I've just started spotting. Is it wrong to make today Cd1? Or does it have to be tomorrow because it's afternoon?
Steeling myself for a family do this evening. If there is a pregnancy announcement you might hear me crying from wherever you are. Just want a couple of glasses of wine and to cry into it at the moment- don't feel at all up to facing 30 family members!
Posted 27 December 2012 - 03:52 PM
QUOTE (rosie28 @ 27/12/2012, 02:18 PM) <{POST_SNAPBACK}>
It just feels like it took so much to get to ovulate at all, what if it never happens again? The timing for next cycle might suck- does anyone know if you can do clomid combined with injectibles?
*nod* I know the feeling all too well... I ended up deciding to be content with the fact that I ovulated last cycle. I was definitely upset that we didn't succeed at making a baby, but I decided to just let me see that month as a victory in its own right.
Now, having gone through the second cycle of that same dose of Clomid, and not seeing success again (in my heart of hearts, I think I didn't O), it's heart breaking. I keep thinking, "what's wrong with me?!!!!! "
I definitely was fretting about the dosage not working again. I totally understand how you can be upset about it Rosie . I hope you didn't think that I meant that you shouldn't be. I guess I was trying to sprinkle a bit of optimism into the mix.
QUOTE (rosie28 @ 27/12/2012, 03:53 PM) <{POST_SNAPBACK}>
And I've just started spotting. Is it wrong to make today Cd1? Or does it have to be tomorrow because it's afternoon?
Steeling myself for a family do this evening. If there is a pregnancy announcement you might hear me crying from wherever you are. Just want a couple of glasses of wine and to cry into it at the moment- don't feel at all up to facing 30 family members!
Oh no..
It might be a nice distraction... possibly? Chin up chickie.
RE spotting - my gynae told me to treat any kind of bleeding, as bleeding therefore spotting = CD1.
This cycle I started spotting at around 11pm-12am, so I didn't call that day CD1, but the next.
I think if I were you, I would just end up deciding that tomorrow is CD1.
Oh chickie You've earned that
Posted 27 December 2012 - 03:56 PM
QUOTE (bek_p @ 27/12/2012, 11:51 AM) <{POST_SNAPBACK}>
Cd 27
seems fairly late in the cycle now. Are you temping?
What's the game plan from here on out? Upping the dose?
Posted 27 December 2012 - 04:29 PM
Thanks Poseidon, I do appreciate the optimism, particularly when I can't muster any of my own!
Ok, so today is CD1. I'm choosing to be positive about the last cycle because first, I ovulated, a major achievement in itself, and second, my LP is 13-14 days, which is good. I also learned about my cycle (or whatever, my clomid cycle), how to temp and read charts and knew enough to know the test would be negative before I took it today. That's kind of comforting in a way, to know what is going on with my body.
Poseidon, forgive my if you've already said, but when do you get your results? You never know, you might have just had a sneaky O (I'm imagining a little eggy dodging a huge thermometer now- and I haven't started drinking, it's a bit of a worry...). I assume you BD'd for Australia throughout the possible O time? If so, you've done everything you can do.
Posted 27 December 2012 - 05:47 PM
QUOTE (rosie28 @ 27/12/2012, 05:29 PM) <{POST_SNAPBACK}>
Thanks Poseidon, I do appreciate the optimism, particularly when I can't muster any of my own!
Ok, so today is CD1. I'm choosing to be positive about the last cycle because first, I ovulated, a major achievement in itself, and second, my LP is 13-14 days, which is good. I also learned about my cycle (or whatever, my clomid cycle), how to temp and read charts and knew enough to know the test would be negative before I took it today. That's kind of comforting in a way, to know what is going on with my body.
Poseidon, forgive my if you've already said, but when do you get your results? You never know, you might have just had a sneaky O (I'm imagining a little eggy dodging a huge thermometer now- and I haven't started drinking, it's a bit of a worry...). I assume you BD'd for Australia throughout the possible O time? If so, you've done everything you can do.
First paragraph - absolutely. That sounds excellent and healthy and you should pat your body on the back for doing what it was meant to
Second paragraph - get my results back, presumably, tomorrow. Otherwise, Monday (boo).
We BD for Australia all cycle long, haha
SOo.. breaking news for me: I went to check my cervix about 5min ago (DH and I were going to BD but I wanted to get an untainted reading of CM first). Blood. Light red blood in my CM. It wasn't period coloured either.
I am freaking the eff out. Is it AF?! Is something wrong with my insides?! And, last but not least, is it implantation bleeding?!
My stomach is in such a knot because I'm so worried as to what it could be. I've never had mid cycle spotting in my entire life
Hah, is my wanting to puke an EPS or just the effect of anxiety? the latter, definitely *sure nod*
ETA: lmao @ the article I Googled:
What can I do if I have an implantation bleed?
Sit tight and don't become anxious.
Edited by Poseidon768, 27 December 2012 - 05:49 PM.
Posted 27 December 2012 - 08:28 PM
Well something is up because I had a bit of a light bleed that stopped, and I had this sharp stabbing pain to the left of my belly button for about an hour - that, too, has stopped.
Will have to call gynae and see what she has to say tomorrow. Hopefully I can get my CD21 results back from her too.
I hope it's not ectopic or anything like that
Edited by Poseidon768, 27 December 2012 - 08:28 PM.
Posted 27 December 2012 - 09:08 PM
for those with BFNs.
Poisedon...fingers crossed that the light bleed and pain was implantation and that the egg is getting snuggly and safe in the right place.
AFM: I will be POAS before new years just in case as I am on 70-100 day cycles currently so I test about monthly just in case I spontaneously ovulate and then manage to catch the egg. New Years will be a big night as I am going to my best friends mum's 50th and there will be lots of drinking involved so need to know if I have a BFP beforehand.
Also in good news, I came third for the women in the 8 week challenge that I finished last week. I will be doing the next challenge starting on the 2nd Jan and am aiming to finish higher this time so that is extra motivation to get out there and work hard. Main issue is eating healthy majority of the time but am getting better at avoiding the junk food temptation. I have given myself a couple of days off over Christmas but am back into the exercise as of today.
I did a personal best in swimming with 2.8km in 95mins which is the longest distance I have ever swum and a pretty decent time as well. Very happy about that.
Hopefully all this hard work will pay off in the baby stakes with my body being in the best fitness it has been for years and the kgs melting off slowly.
Posted 27 December 2012 - 09:30 PM
Perhaps implantation Poseidon, how many days post O are you now?
My spotting has stopped. No idea what is going on! I assume it will come back tomorrow properly, and I'm going to have a chat to the FS about the plan for this cycle.
Have thoroughly enjoyed 3 glasses of bubbly.
Posted 27 December 2012 - 09:50 PM
QUOTE (rosie28 @ 27/12/2012, 10:30 PM) <{POST_SNAPBACK}>
Have thoroughly enjoyed 3 glasses of bubbly.
Well, IF I O'ed (hah, who knows? this is such a confusing mess ), I would be 8DPO.
Posted 27 December 2012 - 10:32 PM
Well you'll know tomorrow, an I bet you did! Sneaky O!
Posted 27 December 2012 - 10:56 PM
I'm starting to think it's AF
Like you said rosie, I'll find out tomorrow! Aaaand the wait continues
So I think it's AF and I just had an annovulatory cycle
Temp is down, nothing about my chart looks biphasic. Oh well
Did get an evap line on the HPT though (confirmed by DH who is less delusional than I am )
Sorry for the false alarm ladies! This has never happened to me before.
Not sure what to do now.....
Edited by Poseidon768, 28 December 2012 - 06:40 AM.
Posted 28 December 2012 - 08:09 AM
Yep. Annovulatory cycle.
Progesterone was 2.1
I think we'll be taking a month's break in Jan.... get ourselves excited and collected again about TTC. To have only ovulated once since March this year has been such a drain (as you all probably know). Need a break.
I'll still hang around though, I want to see your successes
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