dc.contributor.author | Muranen, TA | |
dc.contributor.author | Greco, D | |
dc.contributor.author | Blomqvist, C | |
dc.contributor.author | Aittomäki, K | |
dc.contributor.author | Khan, S | |
dc.contributor.author | Hogervorst, F | |
dc.contributor.author | Verhoef, S | |
dc.contributor.author | Pharoah, PDP | |
dc.contributor.author | Dunning, AM | |
dc.contributor.author | Shah, M | |
dc.contributor.author | Luben, R | |
dc.contributor.author | Bojesen, SE | |
dc.contributor.author | Nordestgaard, BG | |
dc.contributor.author | Schoemaker, M | |
dc.contributor.author | Swerdlow, A | |
dc.contributor.author | García-Closas, M | |
dc.contributor.author | Figueroa, J | |
dc.contributor.author | Dörk, T | |
dc.contributor.author | Bogdanova, NV | |
dc.contributor.author | Hall, P | |
dc.contributor.author | Li, J | |
dc.contributor.author | Khusnutdinova, E | |
dc.contributor.author | Bermisheva, M | |
dc.contributor.author | Kristensen, V | |
dc.contributor.author | Borresen-Dale, A-L | |
dc.contributor.author | NBCS Investigators, | |
dc.contributor.author | Peto, J | |
dc.contributor.author | Dos Santos Silva, I | |
dc.contributor.author | Couch, FJ | |
dc.contributor.author | Olson, JE | |
dc.contributor.author | Hillemans, P | |
dc.contributor.author | Park-Simon, T-W | |
dc.contributor.author | Brauch, H | |
dc.contributor.author | Hamann, U | |
dc.contributor.author | Burwinkel, B | |
dc.contributor.author | Marme, F | |
dc.contributor.author | Meindl, A | |
dc.contributor.author | Schmutzler, RK | |
dc.contributor.author | Cox, A | |
dc.contributor.author | Cross, SS | |
dc.contributor.author | Sawyer, EJ | |
dc.contributor.author | Tomlinson, I | |
dc.contributor.author | Lambrechts, D | |
dc.contributor.author | Moisse, M | |
dc.contributor.author | Lindblom, A | |
dc.contributor.author | Margolin, S | |
dc.contributor.author | Hollestelle, A | |
dc.contributor.author | Martens, JWM | |
dc.contributor.author | Fasching, PA | |
dc.contributor.author | Beckmann, MW | |
dc.contributor.author | Andrulis, IL | |
dc.contributor.author | Knight, JA | |
dc.contributor.author | kConFab/AOCS Investigators, | |
dc.contributor.author | Anton-Culver, H | |
dc.contributor.author | Ziogas, A | |
dc.contributor.author | Giles, GG | |
dc.contributor.author | Milne, RL | |
dc.contributor.author | Brenner, H | |
dc.contributor.author | Arndt, V | |
dc.contributor.author | Mannermaa, A | |
dc.contributor.author | Kosma, V-M | |
dc.contributor.author | Chang-Claude, J | |
dc.contributor.author | Rudolph, A | |
dc.contributor.author | Devilee, P | |
dc.contributor.author | Seynaeve, C | |
dc.contributor.author | Hopper, JL | |
dc.contributor.author | Southey, MC | |
dc.contributor.author | John, EM | |
dc.contributor.author | Whittemore, AS | |
dc.contributor.author | Bolla, MK | |
dc.contributor.author | Wang, Q | |
dc.contributor.author | Michailidou, K | |
dc.contributor.author | Dennis, J | |
dc.contributor.author | Easton, DF | |
dc.contributor.author | Schmidt, MK | |
dc.contributor.author | Nevanlinna, H | |
dc.date.accessioned | 2016-11-24T11:28:17Z | |
dc.date.issued | 2017-05-01 | |
dc.identifier.citation | Genetics in medicine : official journal of the American College of Medical Genetics, 2017, 19 (5), pp. 599 - 603 | |
dc.identifier.issn | 1098-3600 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/280 | |
dc.identifier.eissn | 1530-0366 | |
dc.identifier.doi | 10.1038/gim.2016.147 | |
dc.description.abstract | PURPOSE: CHEK2*1100delC is a founder variant in European populations that confers a two- to threefold increased risk of breast cancer (BC). Epidemiologic and family studies have suggested that the risk associated with CHEK2*1100delC is modified by other genetic factors in a multiplicative fashion. We have investigated this empirically using data from the Breast Cancer Association Consortium (BCAC). METHODS: Using genotype data from 39,139 (624 1100delC carriers) BC patients and 40,063 (224) healthy controls from 32 BCAC studies, we analyzed the combined risk effects of CHEK2*1100delC and 77 common variants in terms of a polygenic risk score (PRS) and pairwise interaction. RESULTS: The PRS conferred odds ratios (OR) of 1.59 (95% CI: 1.21-2.09) per standard deviation for BC for CHEK2*1100delC carriers and 1.58 (1.55-1.62) for noncarriers. No evidence of deviation from the multiplicative model was found. The OR for the highest quintile of the PRS was 2.03 (0.86-4.78) for CHEK2*1100delC carriers, placing them in the high risk category according to UK NICE guidelines. The OR for the lowest quintile was 0.52 (0.16-1.74), indicating a lifetime risk close to the population average. CONCLUSION: Our results confirm the multiplicative nature of risk effects conferred by CHEK2*1100delC and the common susceptibility variants. Furthermore, the PRS could identify carriers at a high lifetime risk for clinical actions.Genet Med advance online publication 06 October 2016. | |
dc.format | Print-Electronic | |
dc.format.extent | 599 - 603 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.subject | NBCS Investigators | |
dc.subject | kConFab/AOCS Investigators | |
dc.subject | Humans | |
dc.subject | Breast Neoplasms | |
dc.subject | Genetic Predisposition to Disease | |
dc.subject | Odds Ratio | |
dc.subject | Sequence Deletion | |
dc.subject | Penetrance | |
dc.subject | Female | |
dc.subject | Genes, Modifier | |
dc.subject | Checkpoint Kinase 2 | |
dc.title | Genetic modifiers of CHEK2*1100delC-associated breast cancer risk. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-07-27 | |
rioxxterms.versionofrecord | 10.1038/gim.2016.147 | |
rioxxterms.licenseref.startdate | 2017-05 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Genetics in medicine : official journal of the American College of Medical Genetics | |
pubs.issue | 5 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Aetiological Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Aetiological Epidemiology | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Aetiological Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Aetiological Epidemiology | |
pubs.publication-status | Published | |
pubs.volume | 19 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Aetiological Epidemiology | |
dc.contributor.icrauthor | Schoemaker, Minouk | |
dc.contributor.icrauthor | Swerdlow, Anthony | |