Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : identification of a modifier of breast cancer risk at locus 11q22.3
Permalink
Citation
Hamdi , Y , Soucy , P , Kuchenbaeker , K B , Pastinen , T , Droit , A , Lemacon , A , Adlard , J , Aittomäki , K , Andrulis , I L , Arason , A , Arnold , N , Arun , B K , Azzollini , J , Bane , A , Barjhoux , L , Barrowdale , D , Benitez , J , Berthet , P , Blok , M J , Bobolis , K , Bonadona , V , Bonanni , B , Bradbury , A R , Brewer , C , Buecher , B , Buys , S S , Caligo , M A , Chiquette , J , Chung , W K , Claes , K B M , Daly , M B , Damiola , F , Davidson , R , De la Hoya , M , De Leeneer , K , Diez , O , Ding , Y C , Dolcetti , R , Domchek , S M , Dorfling , C M , Eccles , D , Eeles , R , Einbeigi , Z , Ejlertsen , B , Engel , C , Evans , D G , Feliubadalo , L , Foretova , L , Fostira , F , Nevanlinna , H , EMBRACE , GEMO Study Collaborators , HEBON & kConFab Investigators 2017 , ' Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : identification of a modifier of breast cancer risk at locus 11q22.3 ' , Breast Cancer Research and Treatment , vol. 161 , no. 1 , pp. 117-134 . https://doi.org/10.1007/s10549-016-4018-2
| Title: | Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : identification of a modifier of breast cancer risk at locus 11q22.3 |
| Author: | Hamdi, Yosr; Soucy, Penny; Kuchenbaeker, Karoline B.; Pastinen, Tomi; Droit, Arnaud; Lemacon, Audrey; Adlard, Julian; Aittomäki, Kristiina; Andrulis, Irene L.; Arason, Adalgeir; Arnold, Norbert; Arun, Banu K.; Azzollini, Jacopo; Bane, Anita; Barjhoux, Laure; Barrowdale, Daniel; Benitez, Javier; Berthet, Pascaline; Blok, Marinus J.; Bobolis, Kristie; Bonadona, Valerie; Bonanni, Bernardo; Bradbury, Angela R.; Brewer, Carole; Buecher, Bruno; Buys, Saundra S.; Caligo, Maria A.; Chiquette, Jocelyne; Chung, Wendy K.; Claes, Kathleen B. M.; Daly, Mary B.; Damiola, Francesca; Davidson, Rosemarie; De la Hoya, Miguel; De Leeneer, Kim; Diez, Orland; Ding, Yuan Chun; Dolcetti, Riccardo; Domchek, Susan M.; Dorfling, Cecilia M.; Eccles, Diana; Eeles, Ros; Einbeigi, Zakaria; Ejlertsen, Bent; Engel, Christoph; Evans, D. Gareth; Feliubadalo, Lidia; Foretova, Lenka; Fostira, Florentia; Nevanlinna, Heli; EMBRACE; GEMO Study Collaborators; HEBON; kConFab Investigators |
| Contributor organization: | Medicum Clinicum Department of Medical and Clinical Genetics HUS Gynecology and Obstetrics Department of Obstetrics and Gynecology |
| Date: | 2017-01 |
| Language: | eng |
| Number of pages: | 18 |
| Belongs to series: | Breast Cancer Research and Treatment |
| ISSN: | 0167-6806 |
| DOI: | https://doi.org/10.1007/s10549-016-4018-2 |
| URI: | http://hdl.handle.net/10138/176716 |
| Abstract: | Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of similar to 320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 x 10(-6)). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk. |
| Subject: |
Breast cancer
Genetic modifiers Differential allelic expression Genetic susceptibility Cis-regulatory variants BRCA1 and BRCA2 mutation carriers OVARIAN-CANCER CYCLIN E-CDK2 HUMAN-CELLS DISEASE NPAT INVESTIGATORS CONSORTIUM DNA 3123 Gynaecology and paediatrics 3122 Cancers 3111 Biomedicine 1184 Genetics, developmental biology, physiology |
| Peer reviewed: | Yes |
| Rights: | cc_by |
| Usage restriction: | openAccess |
| Self-archived version: | publishedVersion |
Files in this item
Total number of downloads: Loading...
| Files | Size | Format | View |
|---|---|---|---|
| s10549_016_4018_2.pdf | 1.016Mb |
View/ |
This item appears in the following Collection(s)
-
Articles from TUHAT CRIS [52299]
Related items
Showing items related by title, author, creator and subject.
-
(2019)Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-Adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572000 deaths and 15.2 million DALYs), and stomach cancer (542000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601000 deaths and 17.4 million DALYs), TBL cancer (596000 deaths and 12.6 million DALYs), and colorectal cancer (414000 deaths and 8.3 million DALYs). Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care. © 2019 American Medical Association. All rights reserved.
-
(2017)Familial risks of lung cancer are well-established, but whether lung cancer clusters with other discordant cancers is less certain, particularly beyond smoking-related sites, which may provide evidence on genetic contributions to lung cancer aetiology. We used a novel approach to search for familial associations in the Swedish Family-Cancer Database. This involved assessment of familial relative risk for cancer X in families with increasing numbers of lung cancer patients and, conversely, relative risks for lung cancer in families with increasing numbers of patients with cancers X. However, we lacked information on smoking. The total number of lung cancers in the database was 125 563. We applied stringent statistical criteria and found that seven discordant cancers were associated with lung cancer among family members, and six of these were known to be connected with smoking: oesophageal, upper aerodigestive tract, liver, cervical, kidney and urinary bladder cancers. A further novel finding was that cancer of unknown primary also associated with lung cancer. We also factored in histological evidence and found that anal and connective tissue cancers could be associated with lung cancer for reasons other than smoking. For endometrial and prostate cancers, suggestive negative associations with lung cancer were found. Although we lacked information on smoking it is prudent to conclude that practically all observed discordant associations of lung cancer were with cancers for which smoking is a risk factor. © ERS 2017.
-
(2018)Background: ECCO essential requirements for quality cancer care (ERQCC) are checklists and explanations of organisation and actions that are necessary to give high-quality care to patients who have a specific type of cancer. They are written by European experts representing all disciplines involved in cancer care. ERQCC papers give oncology teams, patients, policymakers and managers an overview of the elements needed in any healthcare system to provide high quality of care throughout the patient journey. References are made to clinical guidelines and other resources where appropriate, and the focus is on care in Europe. Oesophageal and gastric: essential requirements for quality care: Oesophageal and gastric (OG) cancers are a challenging tumour group with a poor prognosis and wide variation in outcomes among European countries. Increasing numbers of older people are contracting the diseases, and treatments and care pathways are becoming more complex in both curative and palliative settings. High-quality care can only be a carried out in specialised OG cancer units or centres which have both a core multidisciplinary team and an extended team of allied professionals, and which are subject to quality and audit procedures. Such units or centres are far from universal in all European countries. It is essential that, to meet European aspirations for comprehensive cancer control, healthcare organisations implement the essential requirements in this paper, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis, to treatment, to survivorship. Conclusion: Taken together, the information presented in this paper provides a comprehensive description of the essential requirements for establishing a high-quality OG cancer service. The ERQCC expert group is aware that it is not possible to propose a one size fits all' system for all countries, but urges that access to multidisciplinary units or centres must be guaranteed for all those with OG cancer.