Please use this identifier to cite or link to this item: https://doi.org/10.1056/NEJMoa1913948
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dc.titleBreast cancer risk genes - Association analysis in more than 113,000 women
dc.contributor.authorDorling, L
dc.contributor.authorCarvalho, S
dc.contributor.authorAllen, J
dc.contributor.authorGonzalez-Neira, A
dc.contributor.authorLuccarini, C
dc.contributor.authorWahlstrom, C
dc.contributor.authorPooley, KA
dc.contributor.authorParsons, MT
dc.contributor.authorFortuno, C
dc.contributor.authorWang, Q
dc.contributor.authorBolla, MK
dc.contributor.authorDennis, J
dc.contributor.authorKeeman, R
dc.contributor.authorAlonso, MR
dc.contributor.authorAlvarez, N
dc.contributor.authorHerraez, B
dc.contributor.authorFernandez, V
dc.contributor.authorNunez-Torres, R
dc.contributor.authorOsorio, A
dc.contributor.authorValcich, J
dc.contributor.authorLi, M
dc.contributor.authorTongren, T
dc.contributor.authorHarrington, PA
dc.contributor.authorBaynes, C
dc.contributor.authorConroy, DM
dc.contributor.authorDecker, B
dc.contributor.authorFachal, L
dc.contributor.authorMavaddat, N
dc.contributor.authorAhearn, T
dc.contributor.authorAittomaki, K
dc.contributor.authorAntonenkova, NN
dc.contributor.authorArnold, N
dc.contributor.authorArveux, P
dc.contributor.authorAusems, MGEM
dc.contributor.authorAuvinen, P
dc.contributor.authorBecher, H
dc.contributor.authorBeckmann, MW
dc.contributor.authorBehrens, S
dc.contributor.authorBermisheva, M
dc.contributor.authorBialkowska, K
dc.contributor.authorBlomqvist, C
dc.contributor.authorBogdanova, NV
dc.contributor.authorBogdanova-Markov, N
dc.contributor.authorBojesen, SE
dc.contributor.authorBonanni, B
dc.contributor.authorBorresen-Dale, AL
dc.contributor.authorBrauch, H
dc.contributor.authorBremer, M
dc.contributor.authorBriceno, I
dc.contributor.authorBruning, T
dc.contributor.authorBurwinkel, B
dc.contributor.authorCameron, DA
dc.contributor.authorCamp, NJ
dc.contributor.authorCampbell, A
dc.contributor.authorCarracedo, A
dc.contributor.authorCastelao, JE
dc.contributor.authorCessna, MH
dc.contributor.authorChanock, SJ
dc.contributor.authorChristiansen, H
dc.contributor.authorCollee, JM
dc.contributor.authorCordina-Duverger, E
dc.contributor.authorCornelissen, S
dc.contributor.authorCzene, K
dc.contributor.authorDork, T
dc.contributor.authorEkici, AB
dc.contributor.authorEngel, C
dc.contributor.authorEriksson, M
dc.contributor.authorFasching, PA
dc.contributor.authorFigueroa, J
dc.contributor.authorFlyger, H
dc.contributor.authorForsti, A
dc.contributor.authorGabrielson, M
dc.contributor.authorGago-Dominguez, M
dc.contributor.authorGeorgoulias, V
dc.contributor.authorGil, F
dc.contributor.authorGiles, GG
dc.contributor.authorGlendon, G
dc.contributor.authorGomez Garcia, EB
dc.contributor.authorGrenaker Alnaes, GI
dc.contributor.authorGuenel, P
dc.contributor.authorHadjisavvas, A
dc.contributor.authorHaeberle, L
dc.contributor.authorHahnen, E
dc.contributor.authorHall, P
dc.contributor.authorHamann, U
dc.contributor.authorHarkness, EF
dc.contributor.authorHartikainen, JM
dc.contributor.authorHartman, M
dc.contributor.authorHe, W
dc.contributor.authorHeemskerk-Gerritsen, BAM
dc.contributor.authorHillemanns, P
dc.contributor.authorHogervorst, FBL
dc.contributor.authorHollestelle, A
dc.contributor.authorHo, WK
dc.contributor.authorHooning, MJ
dc.contributor.authorHowell, A
dc.contributor.authorHumphreys, K
dc.contributor.authorIdris, F
dc.contributor.authorJakubowska, A
dc.contributor.authorJung, A
dc.contributor.authorLi, J
dc.date.accessioned2021-12-01T12:38:35Z
dc.date.available2021-12-01T12:38:35Z
dc.date.issued2021-02-04
dc.identifier.citationDorling, L, Carvalho, S, Allen, J, Gonzalez-Neira, A, Luccarini, C, Wahlstrom, C, Pooley, KA, Parsons, MT, Fortuno, C, Wang, Q, Bolla, MK, Dennis, J, Keeman, R, Alonso, MR, Alvarez, N, Herraez, B, Fernandez, V, Nunez-Torres, R, Osorio, A, Valcich, J, Li, M, Tongren, T, Harrington, PA, Baynes, C, Conroy, DM, Decker, B, Fachal, L, Mavaddat, N, Ahearn, T, Aittomaki, K, Antonenkova, NN, Arnold, N, Arveux, P, Ausems, MGEM, Auvinen, P, Becher, H, Beckmann, MW, Behrens, S, Bermisheva, M, Bialkowska, K, Blomqvist, C, Bogdanova, NV, Bogdanova-Markov, N, Bojesen, SE, Bonanni, B, Borresen-Dale, AL, Brauch, H, Bremer, M, Briceno, I, Bruning, T, Burwinkel, B, Cameron, DA, Camp, NJ, Campbell, A, Carracedo, A, Castelao, JE, Cessna, MH, Chanock, SJ, Christiansen, H, Collee, JM, Cordina-Duverger, E, Cornelissen, S, Czene, K, Dork, T, Ekici, AB, Engel, C, Eriksson, M, Fasching, PA, Figueroa, J, Flyger, H, Forsti, A, Gabrielson, M, Gago-Dominguez, M, Georgoulias, V, Gil, F, Giles, GG, Glendon, G, Gomez Garcia, EB, Grenaker Alnaes, GI, Guenel, P, Hadjisavvas, A, Haeberle, L, Hahnen, E, Hall, P, Hamann, U, Harkness, EF, Hartikainen, JM, Hartman, M, He, W, Heemskerk-Gerritsen, BAM, Hillemanns, P, Hogervorst, FBL, Hollestelle, A, Ho, WK, Hooning, MJ, Howell, A, Humphreys, K, Idris, F, Jakubowska, A, Jung, A, Li, J (2021-02-04). Breast cancer risk genes - Association analysis in more than 113,000 women. New England Journal of Medicine 384 (5) : 428-439. ScholarBank@NUS Repository. https://doi.org/10.1056/NEJMoa1913948
dc.identifier.issn00284793
dc.identifier.issn15334406
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/209052
dc.description.abstractBACKGROUND Genetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking. METHODS We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes. We evaluated missense-variant associations according to domain and classification of pathogenicity. RESULTS Protein-truncating variants in 5 genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a risk of breast cancer overall with a P value of less than 0.0001. Protein-truncating variants in 4 other genes (BARD1, RAD51C, RAD51D, and TP53) were associated with a risk of breast cancer overall with a P value of less than 0.05 and a Bayesian false-discovery probability of less than 0.05. For protein-truncating variants in 19 of the remaining 25 genes, the upper limit of the 95% confidence interval of the odds ratio for breast cancer overall was less than 2.0. For protein-truncating variants in ATM and CHEK2, odds ratios were higher for estrogen receptor (ER)-positive disease than for ER-negative disease; for protein-truncating variants in BARD1, BRCA1, BRCA2, PALB2, RAD51C, and RAD51D, odds ratios were higher for ER-negative disease than for ER-positive disease. Rare missense variants (in aggregate) in ATM, CHEK2, and TP53 were associated with a risk of breast cancer overall with a P value of less than 0.001. For BRCA1, BRCA2, and TP53, missense variants (in aggregate) that would be classified as pathogenic according to standard criteria were associated with a risk of breast cancer overall, with the risk being similar to that of protein-truncating variants. CONCLUSIONS The results of this study define the genes that are most clinically useful for inclusion on panels for the prediction of breast cancer risk, as well as provide estimates of the risks associated with protein-truncating variants, to guide genetic counseling.
dc.publisherMassachusetts Medical Society
dc.sourceElements
dc.subjectAdolescent
dc.subjectAdult
dc.subjectAge Factors
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectBreast Neoplasms
dc.subjectFemale
dc.subjectGenetic Predisposition to Disease
dc.subjectGenetic Variation
dc.subjectHumans
dc.subjectLogistic Models
dc.subjectMiddle Aged
dc.subjectMutation, Missense
dc.subjectOdds Ratio
dc.subjectRisk
dc.subjectSequence Analysis, DNA
dc.subjectYoung Adult
dc.typeArticle
dc.date.updated2021-11-30T16:30:54Z
dc.contributor.departmentDEPT OF SURGERY
dc.contributor.departmentEPIDEMIOLOGY & PUBLIC HEALTH
dc.description.doi10.1056/NEJMoa1913948
dc.description.sourcetitleNew England Journal of Medicine
dc.description.volume384
dc.description.issue5
dc.description.page428-439
dc.published.statePublished
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