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Background: Germline BRCA mutations are associated with worse prostate cancer (PCa) outcomes; however, the most appropriate management for mutation carriers has not yet been investigated. Objective: To evaluate the response of BRCA carriers to conventional treatments for localised PCa by analysing metastasis-free survival (MFS) and cause-specific survival (CSS) following radical prostatectomy (RP) or external-beam radiation therapy (RT). Design, setting, and participants: Tumour features and outcomes of 1302 patients with local/locally advanced PCa (including 67 BRCA mutation carriers) were analysed. RP was undergone by 535 patients (35 BRCA); 767 received RT (32 BRCA). Median follow-up was 64 mo. Outcome measurements and statistical analysis: Median survival and 3-, 5-, and 10-yr survival rates were estimated using the Kaplan-Meier method. Generated survival curves were compared using the log-rank test. Cox regression analyses were used to assess the prognostic value of BRCA mutations. Results ...
Niraparib achieved its primary endpoint in a phase III ovarian cancer trial, demonstrating prolonged progression-free survival compared to placebo among patients who are germline BRCA mutation carriers; among patients who are not germline BRCA mutation carriers, but who have homologous recombination deficient tumors as determined by the Myriad myChoice HRD test; and overall in patients who are not germline BRCA mutation carriers.. The trial, NOVA, is a double-blind, international trial that enrolled more than 500 patients with recurrent ovarian cancer who were in a response to their most recent platinum-based chemotherapy. There is currently no therapy approved by FDA for maintenance treatment of patients with recurrent ovarian cancer following response to platinum, according to Tesaro Inc., niraparibs sponsor. Niraparib is an oral, once-daily PARP inhibitor. ...
In families of patients with and without BRCA1 mutations, breast and ovarian cancer risks correlate with the patients cancer site. Moreover, in families of breast cancer patients without BRCA mutations, breast cancer risk depends on the patients age at diagnosis. These patterns support the presenc …
Germline BRCA mutation rates in the Latina population are yet to be well described. We aimed to quantitate the rates of referral for genetic testing in qualifyi...
The first patient was enrolled on July 8, 2008 and efficacy and safety data were collected up to the data cut-off of March 26, 2010. Patients were enrolled at 6 centres in Canada. Of the 112 patients who gave informed consent 21 patients failed eligibility criteria or withdrew their consent and were not allocated to treatment ...
Diane Rose, vice president of volunteer programs at the advocacy group FORCE, discusses the importance of mutation testing in cancer (for both men and women), and talks about what it was like undergoing testing, herself, to detect the BRCA mutation (which is linked to the development of several types of cancers ...
A study looks at who is being tested for BRCA mutations as testing becomes more common. Also, a look at the impact of Zika virus on birth defects using benchmark data. Plus: How is the United States doing with infant mortality? ...
Mondays study is the largest yet to show the power of preventive ovarian surgery for those women. The surgery not only lowers their chances of getting either ovarian or breast cancer. The study estimated it also can reduce womens risk of death before age 70 by 77 percent.. Ovarian cancer is particularly deadly, and there is no good way to detect it early like there is for breast cancer. So for years, doctors have advised BRCA carriers to have their ovaries removed between the ages of 35 and 40, or when women are finished having children. The new study suggests the surgery, called an oophorectomy, should be timed differently for the different genes. For women who carry the higher-risk BRCA1, the chance of already having ovarian cancer rose from 1.5 percent at age 35 to 4 percent at age 40, said lead researcher Dr. Steven Narod of the University of Toronto. After that, the risk jumped to 14 percent by age 50.. In contrast, the researchers said carriers of the related BRCA2 gene could safely ...
Prophylactic surgery (e.g. bilateral mastectomy or salpingo-oophorectomy) has been shown to substantially reduce the risk for, as well as mortality from, breast or ovarian cancer in both high-risk women and those who are BRCA mutation carriers ...
Prophylactic surgery (e.g. bilateral mastectomy or salpingo-oophorectomy) has been shown to substantially reduce the risk for, as well as mortality from, breast or ovarian cancer in both high-risk women and those who are BRCA mutation carriers ...
Its true. They minimize the pain and emphasize the fabulous end result. And leave out a few details. My first breast surgeon told me the scar would be so tiny that I could walk buck naked down the French Riviera and no one would suspect I had a lumpectomy. He was wrong, of course...not that being naked on the Riviera was ever a goal of mine.. The surgeon who performed my hysterectomy told me that "it was his best cut ever." Wrong again. Ive sliced raw chuck roast at a better angle. He should have taken the knife skills cooking class with me. My reconstruction surgeon said my "new" stomach would be flat as the wall. Maybe. Ill let you know after I complete 15 years of boot camp. I guess surgeons think that if they appeal to your vanity, youll gladly go under the knife. Frankly, saving my life was incentive enough for me. They could skip the false promises. But apparently they didnt trust Id be that level-headed. So, Im here to tell you BRCA carriers: Get the surgery. Go under the knife. ...
An MSK medical oncologist and geneticist discusses the latest drug approved for breast cancer and how genetic testing can lead to new treatments.
Zhang H, Moisini I, Ajabnoor RM, Turner BM, Daguiar M, Cai X, Gao S, Yang Q, Wang X, Schiffhauer L, Hicks DG. "Frequency, Clinicopathologic Characteristics, and Follow-up of HER2-Positive Nonpleomorphic Invasive Lobular Carcinoma of the Breast." American journal of clinical pathology.. 2019 Nov 30; Epub 2019 Nov 30. 3/ ...
We have presented a strategy for complete gene sequence analysis followed by a unified framework for interpreting non-coding variants that may affect gene expression. This approach distills large numbers of variants detected by NGS to a limited set of variants prioritized as potential deleterious ch …
The sequencing of individual human genomes may soon be routine in certain clinical contexts - for example, to diagnose suspected Mendelian disorders in pediatri...
Mutations in BRCA1 and BRCA2 are responsible for a large proportion of breast-ovarian cancer families. Protein-truncating mutations have been effectively used in the clinical management of familial breast cancer due to their deleterious impact on protein function. However, the majority of missense variants identified throughout the genes continue to pose an obstacle for predictive informative testing due to low frequency and lack of information on how they affect BRCA1/2 function. Phosphorylation of BRCA1 and BRCA2 play an important role in their function as regulators of DNA repair, transcription and cell cycle in response to DNA damage but whether missense variants of uncertain significance (VUS) are able to disrupt this important process is not known. Here we employed a novel approach using NetworKIN which predicts in vivo kinasesubstrate relationship, and evolutionary conservation algorithms SIFT, PolyPhen and Align-GVGD. We evaluated whether 191 BRCA1 and 43 BRCA2 VUS from the Breast Cancer ...
This study confirms previous reports that BRCA2 mutation carriers have an increased risk of developing pancreatic cancer compared with the general population. It also supports previous evidence that BRCA1 mutation carriers have increased pancreatic cancer risk, but with a higher relative risk than that estimated by other studies. Furthermore, the availability of a large number of high-risk pancreatic cancer families negative for BRCA1 and BRCA2 mutations (∼5,200) has provided a unique opportunity to estimate pancreatic cancer risk in non-mutation carriers from families with breast and ovarian cancer.. The association between BRCA2 mutations and pancreatic cancer risk has been previously investigated; individuals from BRCA2 mutation carrier families have been reported to have a pancreatic cancer risk ranging from 2- to 7-fold higher than general population (14,16,17,24). In our study, we observed a relative risk of 5.79 (95% CI, 4.28-7.84), slightly higher than most previous estimates. Unlike ...
OBJECTIVE Women who are carriers of BRCA gene mutations have an elevated lifetime risk of developing breast or ovarian cancer. Although a number of risk-reducing options are currently available to mutation carriers, uncertainty exists in terms of their efficacy. A systematic review of the literature was conducted to describe the utilization of screening and preventive surgery among unaffected mutation carriers in the face of uncertainty. METHODS MEDLINE, PubMed, and CANCERLIT, English-only computerized literature searches were done to identify articles pertaining to decisions made by unaffected BRCA mutation carriers to reduce risk of breast and ovarian cancer. Studies were required to include information on choices taken by at-risk women following disclosure of a positive BRCA test. RESULTS Only seven studies (5 American and 2 Dutch studies) were identified. The proportion of mutation carriers who chose preventive surgery over screening varied widely across the studies, ranging from 0% to 54% for
It was proposed by Henderson and colleagues in 1985 that breast cancer incidence rates closely parallel the lifetime number of ovulatory cycles, in support of the hypothesis that endogenous estrogen and progesterone are important etiologic factors (2). We show here that among BRCA mutation carriers, the cumulative number of ovulatory cycles is not associated with risk. The mean number of ovulatory cycles for the controls was in fact greater (248) than it was for the cases (243), opposite to what we would expect if risk was positively associated with the number of cycles. The negative association between ovulatory cycles achieved and breast cancer risk is a reflection of the declining risk with age. Nevertheless, a number of reproductive factors are important in BRCA1 carriers including age at menarche, breastfeeding, and oophorectomy, whereas only oophorectomy was protective in BRCA2 carriers.. The diminution of risk associated with a delay of menarche by 1 year is approximately 9% and is ...
Research overview. BRCA1/BRCA2 mutations in breast and ovarian cancer. Germline mutations of BRCA1/BRCA2 genes occur in up to 5% of breast cancer patients and 15% of ovarian cancers. These genes are major players in the repair of DNA double strand breaks. BRCA carriers have therefore increased sensitivity to DNA-damaging agents, such as platinum or PARP inhibitors. We recently showed a correlation between the BRCA2 genotype and response to platinum in ovarian cancer patients. Only BRCA2 carriers, harboring mutations located in the RAD51-binding domain (RAD51-BD), have prolonged treatment-free intervals and longer survival, whereas the other BRCA2 carriers did not show a survival benefit. We are currently investigating the impact of BRCA mutations on toxicity and response to chemotherapy in breast cancer patients.. Pathogenesis of high grade serous ovarian carcinoma. ...
Recognition of early changes in the Fallopian tube cells of BRCA gene mutation carriers may be key to new strategies for preventing ovarian cancer that could also reduce the need for invasive surgery.
Risk for aggressive serous/serous-like endometrial cancer was increased in women with BRCA1 mutations, although the overall risk for uterine cancer after risk-reducing salpingo-oophorectomy (RRSO) to remove the fallopian tube and ovary was not increased, according to a new study published online by JAMA Oncology.. RRSO is part of the standard treatment for women with BRCA mutations but the role of accompanying hysterectomy remains controversial. Clarifying the issue is relevant because serous/serous-like subtypes account for only about 10% of uterine cancer cases but more than 40% of deaths due to the disease.. Noah D. Kauff, M.D., of the Duke University Health System, Durham, N.C., and coauthors looked at the risk of uterine cancer after RRSO in women with mutations in the BRAC1 and BRCA2 gene. The study included 1,083 women without a prior or associated hysterectomy. 67.1% had a history of breast cancer and 29.4% of 928 women with data available had used tamoxifen.. Researchers documented ...
The clinical role of BRCA1 and BRCA2 mutation testing for younger women with breast cancer is in rapid transition because of advances in gene sequencing technologies and accumulating evidence for the contribution of BRCA mutation status to acute management of early breast cancer. Women diagnosed with breast cancer are offered genetic counseling and testing for germline mutations in BRCA1 and BRCA2 if they have a strong family history of the disease and/or they meet other criteria which point to a mutation detection rate that exceeds a predefined threshold for her local service. Genetic risk assessment has usually been offered on completion of surgery and adjuvant therapy for a new breast cancer, and routine genetic test results in Australia has to date taken between one and six months from blood draw. In contrast, genetic counseling and testing offered around the time of breast cancer diagnosis aims to provide the patient with genetic information that will assist in the choice of breast cancer ...
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the pCR rate in the breast and lymph nodes from 43% to 57%, a difference that was stat-istically significant (P=.005). As Dr von Minckwitz explained at the 2015 SABCS, this study also showed that the addition of carboplatin significantly improved disease-free survival at 3 years from 76.1% to 85.8% (hazard ratio, 0.56; P=.035).. Regarding the effect of the presence of a BRCA mutation, the GeparSixto trial found that patients who had a germline BRCA mutation had a higher pCR rate with their control chemotherapy regimen (50% for mutated BRCA vs 33% for wild-type BRCA). Despite the higher pCR rate with the control regimen in BRCA-mutated patients, the addition of carboplatin raised it further (to 62%, although the increase was not statistically significant in this relatively small cohort). As in CALGB 40603, achievement of a pCR was associated with marked improvement in disease-free survival in both BRCA-mutated and BRCA-wild type patients.. The GeparSixto investigators also assessed the effect of ...
Approximately one out of every ten ovarian cancer cases is hereditary.. Most hereditary ovarian cancer can be attributed to two mutations in two genes, BRCA 1 (breast cancer gene 1) and BRCA2 (breast cancer gene 2).. Women who inherit a mutation in these genes are at greater risk of developing epithelial ovarian cancer. Lynch syndrome, which refers to a cluster of cancers that are related to a specific gene mutation, is also associated with increased risk of colorectal, uterine and ovarian cancer.. A thorough evaluation of family history (i.e., a history of breast, colorectal or ovarian cancer) can identify women most likely to have a hereditary cancer risk, and genetic testing can determine if these mutations exist. Although having these mutations increases risk, it does not mean a woman will definitely get the disease.. Furthermore, while genetic testing can indicate where there is increased risk and help determine appropriate monitoring, women should consider the psychological and possible ...
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SAN ANTONIO -- Women from BRCA1/2 mutation-positive families do not have an increased risk of breast cancer if they are not mutation carriers, data from a large cohort study suggest.
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Despite the efficacy of novel therapies, patients with MBC are considered incurable (28-30). Tumors that exhibit genomic instability such as HRD, especially those associated with germline BRCA mutations and potentially with other DNA-repair impediments, are promising therapeutic targets of PARPis, regardless of histologic subtype (31). While PARPis show single-agent activity and likely disrupt DNA repair through multiple mechanisms, further potentiation of synthetic lethality by combining PARPis with platinum agents in patients with BRCA-associated cancers is an attractive concept (16) that has shown encouraging results in preliminary clinical studies (9, 32, 33).. We established the MTDs, when combined, for the PARPi veliparib (150 mg BID) and carboplatin (AUC of 5), in our phase I trial. However, cytopenias leading to protocol-specified delays or dose reduction were observed in 75% of the phase I patients during cycles 1-3. In a phase I/Ib dose-escalation study of the PARPi olaparib, grade 3/4 ...
On April 30 at 7:30 PM, Ill be part of a panel on Health Link with Benita Zahn, WMHT TV, to discuss the genetics behind the "Angelina Jolie effect" that has catalyzed testing for the BRCA mutations. ...
A House panel voted to allow employers to require workers to undergo genetic testing or risk paying a penalty of thousands of dollars.
A House panel voted to allow employers to require workers to undergo genetic testing or risk paying a penalty of thousands of dollars.
Purpose: Germline mutations in the BRCA1 and BRCA2 genes confer increased risks for breast cancers. However, the clinical presentation of breast cancer among women who are carriers of the BRCA1 or BRCA2 (BRCA1/2 carriers) mutations is heterogenous. We aimed to identify the effects of the reproductive histories of women with the BRCA1/2 mutations on the clinical presentation of breast cancer. Methods: We retrospectively analyzed clinical data on women with proven BRCA1 and BRCA2 mutations who were recruited to the Korean Hereditary Breast Cancer study, from 2007 to 2014. Results: Among the 736 women who were BRCA1/2 mutation carriers, a total of 483 women had breast cancers. Breast cancer diagnosis occurred at significantly younger ages in women who experienced menarche at ≤ 14 years of age, compared to those who experienced menarche at , 14 years of age (37.38±7.60 and 43.30±10.11, respectively, p, 0.001). Additionally, the number of full-term pregnancies was significantly associated with ...
Breast Cancer is very common among Canadians. The Canadian Breast Cancer Foundation reported in 2014 " 1 in 9 women in Canada is expected to develop breast cancer during her lifetime." Today we are focusing on the genetic aspects of developing breast cancer in the body.. BRCA1 and BRCA2 genes - BRCA1 and BRCA 2 known, as a Breast Cancer Susceptibility Gene 1 and Breast Cancer Susceptibility Gene 2 are human genes and works as tumor suppressors.. How BRCA1 and BRCA2 connect to cancer? When any of those genes mutate, it causes DNA damage and it might not be able to repair properly, and as a results cell can develop additional genetic alterations. Inherited mutations in BRCA1 and BRCA2 then increase the risk of breast and ovarian cancer.. NOTE: BRCA1 and BRCA2 mutations can be inherited from a persons mother or father. Anyone who has inherited a BRCA1 or BRCA2 mutation could be an increase risk of developing breast and ovarian cancer.. Breast cancer statistics - Breast Cancer Society of Canada has ...
Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [hazard ratio (HR) = 1.17, 95%
Rapid developments in cancer genetics have exposed a knowledge vacuum about genetic testing for susceptibility to cancer. Our experience in testing for BRCA1 or BRCA2 mutation in hereditary breast cancer (HBC) syndrome, with counseling about cancer surveillance and management, inclusive of the option of prophylactic surgery, provides some important information. We provided DNA-based (BRCA1, BRCA2 germ-line mutation) findings on 442 patients from 37 HBC families. The top two reasons for receiving genetic test results are for their children and for their own health surveillance. Of those women who have tested positive for BRCA1 and have been counseled, 40% had already developed breast cancer and 6% had already developed ovarian cancer, while in BRCA2 25% had developed breast cancer and 0% had developed ovarian cancer. Of the unaffected women, prior to counseling 59% from BRCA1 and 46% from BRCA2 said they would consider prophylactic mastectomy if their result was positive; 76% of BRCA1 and 50% of BRCA2
The 12 tumors with a hypermethylated BRCA1 promoter were also analyzed for the two BRCA1 founder mutations common in the Ashkenazi Jewish population, BRCA1 185delAG (exon 2) and BRCA1 5382 insC (exon 20), and found to be free of mutation (Table 1) ⇓ . These samples were also analyzed and found to be absent for the BRCA2 6174delT (exon 11) Jewish founder mutation. The lack of a Jewish founder mutation does not, however, rule out the possibility that other BRCA1 mutations are present. The absence of BRCA1 protein staining in 2 of 9 unmethylated OCs suggests that mechanisms other than promoter hypermethylation may also inhibit BRCA1 protein expression.. A relationship between the BRCA and p53 genes has long been suspected, based upon the higher incidence of p53 mutations in tumors with BRCA mutations than in sporadic carcinomas (31, 32, 33) In view of the critical role of p53 in cell cycle regulation, it has been postulated that BRCA1 mutant cells with wild-type p53 are less susceptible to ...
While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04-1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03-1.16, p = ...
TY - JOUR. T1 - Inhibition of BRCT(BRCA1)-phosphoprotein interaction enhances the cytotoxic effect of olaparib in breast cancer cells. T2 - A proof of concept study for synthetic lethal therapeutic option. AU - Pessetto, Ziyan Yuan. AU - Yan, Ying. AU - Bessho, Tadayoshi. AU - Natarajan, Amarnath. PY - 2012/7. Y1 - 2012/7. N2 - Synthetic lethal therapeutic strategy using poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor olaparib in carriers of BRCA1 or BRCA2 mutation has shown promise in clinical settings. Since ≤5 % of patients are BRCA1 or BRCA2 mutation carriers, small molecules that functionally mimic BRCA1 or BRCA2 mutations will extend the synthetic lethal therapeutic option for non-mutation carriers. Here we provide proof of principle for this strategy using a BRCA1 inhibitor peptide 2 that targets the BRCT(BRCA1)-phosphoprotein interaction and mimics the M177R/K BRCA1 mutation. Reciprocal immunoprecipitation and immunoblotting of BRCA1 and Abraxas was used to ...
About 5% to 10% of breast cancers are thought to be hereditary, caused by abnormal genes passed from parent to child.. Genes are particles in cells, contained in chromosomes, and made of DNA (deoxyribonucleic acid). DNA contains the instructions for building proteins. And proteins control the structure and function of all the cells that make up your body.. Most inherited cases of breast cancer are associated with two abnormal genes: BRCA1 (BReast CAncer gene one) and BRCA2 (BReast CAncer gene two).. Everyone has BRCA1 and BRCA2 genes. The function of the BRCA genes is to repair cell damage and keep breast cells growing normally. But when these genes contain abnormalities or mutations that are passed from generation to generation, the genes dont function normally and breast cancer risk increases. Abnormal BRCA1 and BRCA2 genes may account for up to 10% of all breast cancers, or 1 out of every 10 cases.. Having an abnormal BRCA1 or BRCA2 gene doesnt mean you will be diagnosed with breast cancer. ...
Given how BRCA2 is believed to function as a tumour suppressor, assays related to DNA repair are directly relevant to predicting the impact of BRCA2 variants on cancer risk and therapeutic response. Additionally, such assays have demonstrated high sensitivity and specificity for predicting known benign and pathogenic variants. For these reasons, DNA repair-related assays are considered here.21 Since DNA repair-related domains are distributed throughout BRCA2, as discussed earlier, such assays should be based on expression of full-length BRCA2. BRCA2 is even larger than BRCA1 (the protein is ~390 kDa and the cDNA is 10 254 bp). Thus, it has been difficult to express full-length BRCA2 in human cells using a cDNA.69 73 As such, some functional studies of BRCA2 VUS have been based on heterologous expression of full-length BRCA2 variants in mouse ESCs using BACs.71 72 These studies, in the laboratory of Shyam Sharan, focused on VUS in the N-terminal PALB2-binding domain and the C-terminal DBD, where ...
A breast cancer (BRCA) gene test is a blood test to check for specific changes (mutations) in genes that help control normal cell growth. Finding changes in these genes, called BRCA1 and BRCA2, can help determine your chance of developing breast cancer and ovarian cancer. A BRCA gene test does not test for cancer itself. This test is only done for people with a strong family history of breast cancer, ovarian cancer and sometimes for those who already have one of these diseases. Genetic counseling before and after a BRCA test is very important to help you understand the benefits, risks, and possible outcomes of the test.. A womans risk of breast and ovarian cancer is higher if she has BRCA1 or BRCA2 gene changes. Breast cancer is extremely rare in men but BRCA2 gene changes have been linked to male breast cancer and possibly prostate, may also be higher. The gene changes can be inherited from either your mothers or fathers side of the family.. Certain people have a higher chance of inheriting ...
Men with prostate cancer who are carriers of the BRCA2 gene mutation have significantly increased mortality rates.. The study identified 938 families with the BRCA2 mutation, of which 277 (29.5%) contained one or more cases of prostate cancer, with a total of 434 cases. Of these, 67 men were found to carry the familial BRCA2 mutation and 116 were probable mutation carriers. A comparison group of men with the BRCA1 mutation was also identified. Of 1,735 families, 316 contained one or more cases of prostate cancer (18.2%), with a total of 457 cases. Of these, 37 carried the BRCA1 mutation and 82 men were probable carriers. The average age at diagnosis was similar for the two groups.. Survival analysis was performed to establish the overall survival of BRCA2 carriers with prostate cancer and relative survival compared with BRCA1 carriers. The median survival time was 4.0 years for the BRCA2 group compared with 8.0 years for the BRCA1 group, and the risk of mortality was found to be 70% greater in ...
This study aimed to determine whether telomere length (TL) is a marker of cancer risk or genetic status amongst two cohorts of BRCA1 and BRCA2 mutation carriers and controls. The first group was a prospective set of 665 male BRCA1/2 mutation carriers and controls (mean age 53 years), all healthy at time of enrollment and blood donation, 21 of whom have developed prostate cancer whilst on study. The second group consisted of 283 female BRCA1/2 mutation carriers and controls (mean age 48 years), half of whom had been diagnosed with breast cancer prior to enrollment. TL was quantified by qPCR from DNA extracted from peripheral blood lymphocytes. Weighted and unweighted Cox regressions and linear regression analyses were used to assess whether TL was associated with BRCA1/2 mutation status or cancer risk. We found no evidence for association between developing cancer or being a BRCA1 or BRCA2 mutation carrier and telomere length. It is the first study investigating TL in a cohort of genetically ...
Our study reaffirms that specific BRCA1 and BRCA2 mutations found previously to recur in French Canadian breast cancer and breast-ovarian cancer families, also recur in women with ovarian cancer not selected for family history of cancer. This is especially evident with the number of BRCA1:C4446T mutation carriers (n = 15) identified in this study, which has been the most commonly reported mutation identified in this population and this has been attributed to shared ancestry as a consequence of common founders [24,25,27-29,32,33]. This mutation was also the most common mutation found in our previous study of 74 women with serous and endometrioid ovarian cancers screened for specific BRCA1/BRCA2 mutations [36].. Our study also highlights the significance of the BRCA2:E3002K mutation in the French Canadian population. We found five E3002K mutation-positive carriers in the cohort of 439 women with ovarian cancer, which is similar in frequency to the number of carriers of each of the other three ...
TY - JOUR. T1 - Genetic testing in an ethnically diverse cohort of high-risk women. T2 - A comparative analysis of BRCA1 and BRCA2 mutations in American families of European and African ancestry. AU - Nanda, Rita. AU - Schumm, L. Philip. AU - Cummings, Shelly. AU - Fackenthal, James D.. AU - Sveen, Lise. AU - Ademuyiwa, Foluso. AU - Cobleigh, Melody. AU - Esserman, Laura. AU - Lindor, Noralane Morey. AU - Neuhausen, Susan L.. AU - Olopade, Olufunmilayo I.. PY - 2005/10/19. Y1 - 2005/10/19. N2 - Context: Ten years after BRCA1 and BRCA2 were first identified as major breast cancer susceptibility genes, the spectrum of mutations and modifiers of risk among many ethnic minorities remain undefined. Objectives: To characterize the clinical predictors, spectrum, and frequency of BRCA1 and BRCA2 mutations in an ethnically diverse high-risk clinic population and to evaluate the performance of the BRCAPRO statistical model in predicting the likelihood of a mutation. Design, Setting, and Participants: ...
The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific