Please use this identifier to cite or link to this item: https://doi.org/10.1186/s13073-021-00978-9
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dc.titleGermline breast cancer susceptibility genes, tumor characteristics, and survival
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.accessioned2022-10-26T08:59:58Z
dc.date.available2022-10-26T08:59:58Z
dc.date.issued2021-12-01
dc.identifier.citationHo, Peh Joo, Khng, Alexis J., Loh, Hui Wen, Ho, Weang-Kee, Yip, Cheng Har, Mohd-Taib, Nur Aishah, Tan, Veronique Kiak Mien, Tan, Benita Kiat-Tee, Tan, Su-Ming, Tan, Ern Yu, Lim, Swee Ho, Jamaris, Suniza, Sim, Yirong, Wong, Fuh Yong, Ngeow, Joanne, Lim, Elaine Hsuen, Tai, Mei Chee, Wijaya, Eldarina Azfar, Lee, Soo Chin, Chan, Ching Wan, Buhari, Shaik Ahmad, Chan, Patrick M. Y., Chen, Juliana J. C., Seah, Jaime Chin Mui, Lee, Wai Peng, Mok, Chi Wei, Lim, Geok Hoon, Woo, Evan, Kim, Sung-Won, Lee, Jong Won, Lee, Min Hyuk, Park, Sue K., Dunning, Alison M., Easton, Douglas F., Schmidt, Marjanka K., Teo, Soo-Hwang, Li, Jingmei, Hartman, Mikael (2021-12-01). Germline breast cancer susceptibility genes, tumor characteristics, and survival. Genome Medicine 13 (1) : 185. ScholarBank@NUS Repository. https://doi.org/10.1186/s13073-021-00978-9
dc.identifier.issn1756-994X
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/233529
dc.description.abstractBackground: 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. © 2021, The Author(s).
dc.publisherBioMed Central Ltd
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceScopus OA2021
dc.subjectBreast cancer
dc.subjectOverall survival
dc.subjectProtein-truncating variants
dc.typeArticle
dc.contributor.departmentDEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL)
dc.contributor.departmentDEPT OF SURGERY
dc.contributor.departmentSAW SWEE HOCK SCHOOL OF PUBLIC HEALTH
dc.contributor.departmentDEPT OF MEDICINE
dc.description.doi10.1186/s13073-021-00978-9
dc.description.sourcetitleGenome Medicine
dc.description.volume13
dc.description.issue1
dc.description.page185
dc.published.statePublished
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