Abstract：
:African-American women are more likely to develop aggressive breast cancer at younger ages and experience poorer cancer prognoses than non-Hispanic Caucasians. Deficiency in repair of DNA by homologous recombination (HR) is associated with cancer development, suggesting that mutations in genes that affect this process may cause breast cancer. Inherited pathogenic mutations have been identified in genes involved in repairing DNA damage, but few studies have focused on African-Americans. We screened for germline mutations in seven HR repair pathway genes in DNA of 181 African-American women with breast cancer, evaluated the potential effects of identified missense variants using in silico prediction software, and functionally characterized a set of missense variants by yeast two-hybrid assays. We identified five likely-damaging variants, including two PALB2 truncating variants (Q151X and W1038X) and three novel missense variants (RAD51C C135R, and XRCC3 L297P and V337E) that abolish protein-protein interactions in yeast two-hybrid assays. Our results add to evidence that HR gene mutations account for a proportion of the genetic risk for developing breast cancer in African-Americans. Identifying additional mutations that diminish HR may provide a tool for better assessing breast cancer risk and improving approaches for targeted treatment.
journal_name
Fam Cancerjournal_title
Familial cancerauthors
Ding YC,Adamson AW,Steele L,Bailis AM,John EM,Tomlinson G,Neuhausen SLdoi
10.1007/s10689-017-0036-4subject
Has Abstractpub_date
2018-04-01 00:00:00pages
187-195issue
2eissn
1389-9600issn
1573-7292pii
10.1007/s10689-017-0036-4journal_volume
17pub_type
杂志文章相关文献
Familial Cancer文献大全abstract：:Somerset has a relatively high incidence of cancer. The county is very rural with pockets of deprivation and sizeable areas of poor access to services. The Cancer Plan advocates early identification of cancer and identified the genetic revolution as having the potential to predict risk, and detect and diagnose cancer ...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-007-9133-0
更新日期：2007-01-01 00:00:00
abstract：:The Dutch Hereditary Cancer Registry was established in 1985 with the support of the Ministry of Health (VWS). The aims of the registry are: (1) to promote the identification of families with hereditary cancer, (2) to encourage the participation in surveillance programs of individuals at high risk, (3) to ensure the c...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-016-9897-1
更新日期：2016-07-01 00:00:00
abstract：:Approximately 39.6% of people will be diagnosed with cancer during their lifetime. Several factors including, lifestyle, environment and genetics may play a role in its development. Understanding these causes will greatly improve treatment methods, prevention, and survival rates of these patients. Our patient, who has...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-017-9982-0
更新日期：2017-10-01 00:00:00
abstract：:Ovarian cancer is the fourth leading cause of cancer deaths among American women. While women in both the Ashkenazi and non-Ashkenazi populations have an estimated 1.7% lifetime risk of acquiring malignancy, the proportion of hereditary ovarian cancer is much higher in the Ashkenazim. Most of this increased proportion...
journal_title：Familial cancer
pub_type： 杂志文章,评审
doi：10.1007/s10689-004-9552-0
更新日期：2004-01-01 00:00:00
abstract：:Hereditary diffuse gastric cancer has an early onset and poor prognosis, therefore, individuals who carry a pathogenic (CDH1) mutation in the E-cadherin gene (CDH1) are offered endoscopic surveillance and advised to undergo prophylactic total gastrectomy (PTG) in their early to mid-twenties. Patients not ready or fit ...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-016-9910-8
更新日期：2016-10-01 00:00:00
abstract：:One of a pair of monozygous twins was diagnosed and died of small cell carcinoma of the ovary of hypercalcemic type (SCCOHT) at the age of 30 years. Her sister remained unaffected and was very concerned about her risk for developing SCCOHT. By performing comprehensive molecular analysis using whole exome sequencing (W...
journal_title：Familial cancer
pub_type： 信件
doi：10.1007/s10689-018-0108-0
更新日期：2019-04-01 00:00:00
abstract：:The invalidation of the Mismatch Repair (MMR) system is responsible for a so-called "deficient MMR" phenotype (dMMR) characterized by microsatellite instability and abnormal pattern of expression of MMR proteins in tumor tissue. This phenotype occurs in at least 20% of sporadic endometrial adenocarcinomas by epigeneti...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-017-0032-8
更新日期：2018-04-01 00:00:00
abstract：:This study reports a randomized clinical trial evaluating the efficacy of an intervention to prepare individuals to communicate BRCA1/BRCA2 results to family members. Women aged 18 years and older, who had genetic testing, and who had adult first-degree relatives, were randomly assigned to a communication skills-build...
journal_title：Familial cancer
pub_type： 杂志文章,随机对照试验
doi：10.1007/s10689-013-9609-z
更新日期：2013-09-01 00:00:00
abstract：:Familial adenomatous polyposis (FAP) provides a model for sporadic colorectal cancer development. Cyclooxygenase (COX) inhibition may ameliorate polyp development, but rofecoxib was withdrawn due to cardiovascular side effects. Although this selective COX-2 inhibitor, like diet, may alter the fatty acid and eicosanoid...
journal_title：Familial cancer
pub_type： 杂志文章,随机对照试验
doi：10.1007/s10689-010-9365-2
更新日期：2010-12-01 00:00:00
abstract：:We recently described a novel g.8097_22733del14637 deletion encompassing exons 3-5 in BRCA1 gene. This rearrangement was detected in 3 of 15 (20 %) breast and/or ovarian cancer families of Eastern Spain. This finding made us suspect that the newly identified deletion could be a founder mutation. To confirm this hypoth...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-012-9579-6
更新日期：2013-03-01 00:00:00
abstract：:Li-Fraumeni Syndrome (LFS) is characterized by risk of multiple primary malignancies in diverse sites, pediatric onset, near complete penetrance by age 70 years, limited options for prevention, and substantial uncertainty regarding disease manifestation and prognosis. Forty-five families, including 117 individuals age...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-020-00173-6
更新日期：2020-07-01 00:00:00
abstract：:We assessed mismatch repair by immunohistochemistry (IHC) and microsatellite instability (MSI) analysis in an early onset endometrial cancer and a sister's colon cancer. We demonstrated high-level MSI and normal expression for MLH1, MSH2 and MSH6. PMS2 failed to stain in both tumors, strongly implicating a PMS2 defect...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-009-9276-2
更新日期：2009-01-01 00:00:00
abstract：:Familial Adenomatous Polyposis (FAP) is a model for the adenoma-carcinoma sequence in several respects. One important area in which FAP serves as a model is chemoprevention. Early prevention trials mainly utilized micronutrients and were largely unsuccessful in preventing or causing regression of adenomas. A new era w...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-007-9158-4
更新日期：2008-01-01 00:00:00
abstract：:To support persons having a genetic predisposition to cancer and their partners during reproductive decision-making, an online decision aid was developed and evaluated. To maximize the impact of the support tool, this mixed methods study aims at developing the optimal implementation strategy for the decision aid. A qu...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-019-00119-7
更新日期：2019-04-01 00:00:00
abstract：:Prediction models for the identification of Lynch syndrome have been developed to quantify an individual's risk of carrying a mismatch repair gene mutation and help clinicians decide for whom further risk assessment and genetic testing is necessary. There are diverse clinical settings in which a healthcare provider ha...
journal_title：Familial cancer
pub_type： 杂志文章,评审
doi：10.1007/s10689-013-9632-0
更新日期：2013-06-01 00:00:00
abstract：:Dominantly inherited syndromes of colorectal cancer predisposition are characterized by multifocal neoplasia with an early age of onset. The risk of colorectal cancer is high in affected patients and care of the patients is based on the aims of cancer prevention and cancer cure. At the same time, quality of life shoul...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-016-9886-4
更新日期：2016-07-01 00:00:00
abstract：PURPOSE:The aim of the present descriptive study was to investigate the experience of sharing genetic information among cancer genetic counselees and their at-risk relatives. METHODS:In total, 147 cancer genetic counselees and 81 of their at-risk relatives answered to a study specific questionnaire and/or were intervi...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-010-9364-3
更新日期：2010-12-01 00:00:00
abstract：:To evaluate perceived pain during repetitive annual endometrial sampling at gynaecologic surveillance in asymptomatic women with Lynch syndrome (LS) over time and in addition to symptomatic women without LS, undergoing single endometrial sampling. In this prospective study, 52 women with LS or first degree relatives w...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-016-9937-x
更新日期：2017-04-01 00:00:00
abstract：:Founder mutations in BRCA1/2 genes have been detected in several Jewish communities in Israel, including in Ashkenazi Jews and Jews who immigrated to Israel from Iraq, Yemen, Iran and Afghanistan. We analyzed DNA samples of patients of Sephardic origin (descendents of Jews from the Iberian Peninsula) with breast cance...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-010-9395-9
更新日期：2011-03-01 00:00:00
abstract：:The hereditary forms of colorectal cancer have been given many names historically as the manifestations have been gradually understood. Lynch syndrome has had several names, most prominently 'Hereditary Nonpolyposis Colorectal Cancer' or HNPCC. Clarification of the genetic basis and full phenotypic expression of this ...
journal_title：Familial cancer
pub_type： 杂志文章,评审
doi：10.1007/s10689-004-4489-x
更新日期：2005-01-01 00:00:00
abstract：:Inherited colorectal cancer predisposition involves a rather heterogeneous range of rare, yet relatively well-defined disorders, including Familial Adenomatous Polyposis (FAP), Hereditary Non-polyposis Colorectal Cancer (HNPCC) or Lynch syndrome, Peutz-Jeghers syndrome, Juvenile Polyposis, and their respective variant...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-007-9159-3
更新日期：2008-01-01 00:00:00
abstract：:Infantile and childhood hepatoblastoma (HB) occurs more frequently in children with hereditary predisposition to familial adenomatous polyposis (FAP) than in the general population. The occurrence of HB in two infant siblings is reported. The sister died of the disease. The brother survived the HB and was later diagno...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-012-9538-2
更新日期：2012-09-01 00:00:00
abstract：:Colorectal cancer (CRC) risk associated with germline monoallelic MUTYH mutations remains controversial, although a slightly increased risk for this disease has been suggested. MUTYH and MSH6 proteins act in cooperation during the DNA repair process. Based on this interaction, it was hypothesized that the combination ...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-009-9282-4
更新日期：2009-01-01 00:00:00
abstract：:Muir-Torre syndrome (MTS) is a rare cancer-predisposing syndrome that is autosomal dominantly inherited and characterized by the development of sebaceous skin lesions (adenomas, epitheliomas, basaliomas and carcinomas). These lesions are typically associated with tumors that belong to the spectrum of hereditary nonpol...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-006-9105-9
更新日期：2007-01-01 00:00:00
abstract：:Clinical practice guidelines discourage pediatric genetic testing for BRCA1/2 mutations due to a lack of timely medical benefit and psychosocial risk. Yet, some high risk families approach primary care providers (PCPs) about testing adolescents, and little is known about PCPs attitudes regarding these requests. We ass...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-009-9243-y
更新日期：2010-03-01 00:00:00
abstract：:New Zealand Māori have a considerably higher incidence of gastric cancer compared to non-Māori, and are one of the few populations worldwide with a higher prevalence of diffuse-type disease. Pathogenic germline CDH1 mutations are causative of hereditary diffuse gastric cancer, a cancer predisposition syndrome primaril...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-018-0080-8
更新日期：2019-01-01 00:00:00
abstract：:Following the identification in a proband of a germline BRCA1/BRCA2 mutation in hereditary breast-ovarian cancer (HBOC) or a DNA mismatch repair gene mutation in Lynch syndrome (LS) he or she will be asked to inform at-risk family members about the option for presymptomatic DNA testing. However, in clinical practice m...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-018-0089-z
更新日期：2019-01-01 00:00:00
abstract：:Desmoid tumors occur with high frequency in individuals with Familial Adenomatous Polyposis (FAP). Because of this, individuals developing desmoid tumors may be referred for genetic risk assessment. Determining whether a person has a FAP-related desmoid tumor or a sporadic desmoid can be challenging. We sought to char...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-005-5959-5
更新日期：2006-01-01 00:00:00
abstract：:Distress levels among female BRCA1/2 mutation carriers can be similar to levels found among breast cancer patients. While psychological distress has been associated with unmet needs among cancer patients no study has examined this among BRCA1/2 mutation carriers. The objectives of this study were to: (1) describe the ...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-012-9596-5
更新日期：2013-09-01 00:00:00
abstract：:Assessing adherence behavior among mutation carriers to cancer risk management guidelines is important for both service improvement and cost-effectiveness analyses, but such real-world data is often lacking. The present study aims to report adherence rates among mutation carriers in a recently established cancer genet...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-018-0071-9
更新日期：2018-10-01 00:00:00
