Show simple item record

dc.contributor.authorHo, Peh Joo
dc.contributor.authorKhng, Alexis J.
dc.contributor.authorLoh, Hui Wen
dc.contributor.authorHo, Weang-Kee
dc.contributor.authorYip, Cheng Har
dc.contributor.authorMohd-Taib, Nur Aishah
dc.contributor.authorTan, Veronique Kiak Mien
dc.contributor.authorTan, Benita Kiat-Tee
dc.contributor.authorTan, Su-Ming
dc.contributor.authorTan, Ern Yu
dc.contributor.authorLim, Swee Ho
dc.contributor.authorJamaris, Suniza
dc.contributor.authorSim, Yirong
dc.contributor.authorWong, Fuh Yong
dc.contributor.authorNgeow, Joanne
dc.contributor.authorLim, Elaine Hsuen
dc.contributor.authorTai, Mei Chee
dc.contributor.authorWijaya, Eldarina Azfar
dc.contributor.authorLee, Soo Chin
dc.contributor.authorChan, Ching Wan
dc.contributor.authorBuhari, Shaik Ahmad
dc.contributor.authorChan, Patrick M. Y.
dc.contributor.authorChen, Juliana J. C.
dc.contributor.authorSeah, Jaime Chin Mui
dc.contributor.authorLee, Wai Peng
dc.contributor.authorMok, Chi Wei
dc.contributor.authorLim, Geok Hoon
dc.contributor.authorWoo, Evan
dc.contributor.authorKim, Sung-Won
dc.contributor.authorLee, Jong Won
dc.contributor.authorLee, Min Hyuk
dc.contributor.authorPark, Sue K.
dc.contributor.authorDunning, Alison M.
dc.contributor.authorEaston, Douglas F.
dc.contributor.authorSchmidt, Marjanka K.
dc.contributor.authorTeo, Soo-Hwang
dc.contributor.authorLi, Jingmei
dc.contributor.authorHartman, Mikael
dc.date.accessioned2021-12-15T16:27:08Z
dc.date.available2021-12-15T16:27:08Z
dc.date.issued2021-12-02
dc.date.submitted2021-03-25
dc.identifier.others13073-021-00978-9
dc.identifier.other978
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331520
dc.description.abstractAbstract: Background: Mutations in certain genes are known to increase breast cancer risk. We study the relevance of rare protein-truncating variants (PTVs) that may result in loss-of-function in breast cancer susceptibility genes on tumor characteristics and survival in 8852 breast cancer patients of Asian descent. Methods: Gene panel sequencing was performed for 34 known or suspected breast cancer predisposition genes, of which nine genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, and TP53) were associated with breast cancer risk. Associations between PTV carriership in one or more genes and tumor characteristics were examined using multinomial logistic regression. Ten-year overall survival was estimated using Cox regression models in 6477 breast cancer patients after excluding older patients (≥75years) and stage 0 and IV disease. Results: PTV9genes carriership (n = 690) was significantly associated (p < 0.001) with more aggressive tumor characteristics including high grade (poorly vs well-differentiated, odds ratio [95% confidence interval] 3.48 [2.35–5.17], moderately vs well-differentiated 2.33 [1.56–3.49]), as well as luminal B [HER−] and triple-negative subtypes (vs luminal A 2.15 [1.58–2.92] and 2.85 [2.17–3.73], respectively), adjusted for age at diagnosis, study, and ethnicity. Associations with grade and luminal B [HER2−] subtype remained significant after excluding BRCA1/2 carriers. PTV25genes carriership (n = 289, excluding carriers of the nine genes associated with breast cancer) was not associated with tumor characteristics. However, PTV25genes carriership, but not PTV9genes carriership, was suggested to be associated with worse 10-year overall survival (hazard ratio [CI] 1.63 [1.16–2.28]). Conclusions: PTV9genes carriership is associated with more aggressive tumors. Variants in other genes might be associated with the survival of breast cancer patients. The finding that PTV carriership is not just associated with higher breast cancer risk, but also more severe and fatal forms of the disease, suggests that genetic testing has the potential to provide additional health information and help healthy individuals make screening decisions.
dc.languageen
dc.publisherBioMed Central
dc.subjectResearch
dc.subjectBreast cancer
dc.subjectProtein-truncating variants
dc.subjectOverall survival
dc.titleGermline breast cancer susceptibility genes, tumor characteristics, and survival
dc.typeArticle
dc.date.updated2021-12-15T16:27:07Z
prism.issueIdentifier1
prism.publicationNameGenome Medicine
prism.volume13
dc.identifier.doi10.17863/CAM.78974
dcterms.dateAccepted2021-09-24
rioxxterms.versionofrecord10.1186/s13073-021-00978-9
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidLi, Jingmei [0000-0001-8587-7511]
dc.identifier.eissn1756-994X
pubs.funder-project-idNational Medical Research Council (NMRC/CSA-SI/0015/2017, NMRC/CG/NCIS/2010, NMRC/CG/012/2013, CGAug16M005, CGAug16M012)
pubs.funder-project-idNational Research Foundation Singapore (NRF-NRFF2017-02)


Files in this item

Thumbnail
Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record