Genome- and transcriptome-wide association studies of 386,000 Asian and European-ancestry women provide new insights into breast cancer genetics

Jia, Guochong; Ping, Jie; Shu, Xiang; Yang, Yaohua; Cai, Qiuyin; Kweon, Sun‐Seog; Choi, Ji‐Yeob; Kubo, Michiaki; Park, Sung Sup; Bolla, Manjeet K.; Dennis, Joe; Wang, Qin; Li, Bingshan; Tao, Ran; Aronson, Kristan J.; Chan, Tsun Leung; Gao, Yu‐Tang; Hartman, Mikael; Ho, Weang Kee; Ito, Hidemi; Iwasaki, Motoki; Iwata, Hiroji; John, Esther M.; Kasuga, Yoshio; Kim, Mi-Kyung; Kurian, Allison W.; Kwong, Ava; Li, Jingmei; Lophatananon, Artitaya; Low, Siew‐Kee; Mariapun, Shivaani; Matsuda, Koichi; Matsuo, Keitaro; Muir, Kenneth; Noh, Dong‐Young; Park, Boyoung; Park, Min‐Ho; Shen, Chen‐Yang; Shin, Min‐Ho; Spinelli, John J.; Takahashi, Atsushi; Tseng, Chiu-Chen; Tsugane, Shoichiro; Wu, Anna H.; Yamaji, Taiki; Zheng, Ying; Dunning, Alison M.; Pharoah, Paul D.P.; Teo, Soo‐Hwang; Kang, Daehee; Easton, Douglas F.; Simard, Jacques; Shu, Xiao‐Ou; Long, Jirong; Wang, Zheng

doi:10.1016/j.ajhg.2022.10.011

Cited by 16 publications

(15 citation statements)

References 55 publications

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“…Of the 21 proteins identified in previous GWAS-identified loci for breast cancer, 10 proteins were no longer significantly associated with breast cancer risk after index variant adjustment, suggesting that these proteins are likely protein targets at the risk loci. Some encoding genes of the identified proteins are also the nearest protein-coding genes of the reported index variants (AKR1A1, GSTM2, TLR1 and PDCD6), or have been reported as potential target genes by previous TWAS [5][6][7][8][9] (GSTM1, GSTM2, GSTM4, SEMA4A, TLR1, GDI2, NTN4, SNUPN, NAGLU and CPNE1). Our findings are also supported by a previous study which reported TLR1 and NTN4…”

Section: Discussionmentioning

confidence: 99%

Identification of target proteins for breast cancer genetic risk loci and blood risk biomarkers in a large study by integrating genomic and proteomic data

Jia

Yang

Ping

et al. 2023

Intl Journal of Cancer

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Genome-wide association studies (GWAS) have identified around 200 loci associated with breast cancer risk. However, protein targets for these loci remain largely unknown. Identifying protein targets and biomarkers can improve the understanding of cancer biology and etiology and identify high-risk individuals for cancer prevention. In this study, we investigated genetically predicted levels of 1142 circulating proteins with breast cancer risk in 133 384 cases and 113 789 controls of European ancestry included in the Breast Cancer Association Consortium (BCAC). We identified 22 blood protein biomarkers associated with the risk of overall breast cancer at a false discovery rate (FDR) <0.05, including nine proteins encoded by genes located at least 500 kb away from previously reported risk variants for breast cancer. Analyses focusing on 124 encoding genes located at GWAS-identified breast cancer risk loci found 20 proteins associated with overall breast cancer risk and one protein associated with triple-negative breast cancer risk at FDR <0.05. Adjustment for the GWAS-identified risk variants significantly attenuated the association for 13 of these proteins, suggesting that these proteins may be the targets of these GWAS-identified risk loci. The identified proteins are involved in various biological processes, including glutathione conjugation, STAT5 signaling and NF-κB signaling pathways. Our study identified novel protein targets and risk biomarkers for breast cancer risk.

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Section: Discussionmentioning

confidence: 99%

Identification of target proteins for breast cancer genetic risk loci and blood risk biomarkers in a large study by integrating genomic and proteomic data

Jia

Yang

Ping

et al. 2023

Intl Journal of Cancer

Self Cite

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“…Due to the large number of variants being investigated, in order to describe these risks it was necessary to conduct increasingly large-scale studies with increasingly large numbers of cases – not only because of the sometimes marginal influence of individual variants, but also because of the difficulties in dealing with multiple tests when performing a large number of statistical tests. The largest study conducted to date in this context has now been published 1 . This study includes data from 160 500 breast cancer patients and 226 196 control subjects.…”

Section: Preventionmentioning

confidence: 99%

“…As standard, the patients were given dose-dense doxorubicin and cyclophosphamide, followed by treatment with paclitaxel in combination with trastuzumab and pertuzumab. The patients ▶ Table 1 Newly discovered gene loci that have been found to have an association with breast cancer risk (according to [1]).…”

Section: Atezolizumab In Neoadjuvant Therapymentioning

confidence: 99%

“…Für die Beschreibung dieser Risiken waren wegen der hohen Anzahl untersuchter Varianten immer größere Studien mit immer größeren Fallzahlen notwendig, nicht nur wegen des teilweise geringen Einflusses der einzelnen Varianten, sondern auch wegen der Problematik des multiplen Testens bei einer hohen Anzahl durchgeführter statistischer Tests. Nun ist die bislang größte Studie in diesem Zusammenhang veröffentlicht worden [1]. In dieser Studie sind Daten von 160 500 Patientinnen mit Mammakarzinom und von 226 196 gesunden Kontrollpersonen zusammen untersucht worden.…”

Section: Größte Studie Zu Neuen Risikovarianten Veröffentlichtunclassified

“…Es ▶ Tab. 1 Neu entdeckte Genloci, die mit dem Brustkrebsrisiko in Verbindung gebracht werden konnten (nach [1]). verbessert das ereignisfreie Überleben signifikant, und die Daten zum Gesamtüberleben deuten ebenfalls auf eine Verlängerung hin, allerdings ist der Unterschied noch nicht statistisch signifikant [15].…”

Section: Atezolizumab In Der Neoadjuvanzunclassified

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Update Breast Cancer 2022 Part 5 – Early Stage Breast Cancer

Fehm

Welslau

Müller

et al. 2023

Geburtshilfe Frauenheilkd

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The treatment of patients with early stage breast cancer has changed in recent years due to the introduction of pembrolizumab, olaparib, and abemaciclib. These and other drugs with the same class of active ingredient are currently in trial for various indications. This review article summarizes the latest results that have either been presented at major conferences such as the ESMO 2022 or published recently in international journals. This includes reports on newly discovered breast cancer genes, atezolizumab in neoadjuvant therapy in HER2-positive patients, long-term data from the APHINITY study, and on how preoperative peritumoral application of local anesthetics can influence the prognosis. We also present solid data on dynamic Ki-67 from the ADAPT studies.

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A joint transcriptome-wide association study across multiple tissues identifies candidate breast cancer susceptibility genes

Fiorica

McClellan

Barbeira

et al. 2023

The American Journal of Human Genetics

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Genome- and transcriptome-wide association studies of 386,000 Asian and European-ancestry women provide new insights into breast cancer genetics

Cited by 16 publications

References 55 publications

Identification of target proteins for breast cancer genetic risk loci and blood risk biomarkers in a large study by integrating genomic and proteomic data

Identification of target proteins for breast cancer genetic risk loci and blood risk biomarkers in a large study by integrating genomic and proteomic data

Update Breast Cancer 2022 Part 5 – Early Stage Breast Cancer

A joint transcriptome-wide association study across multiple tissues identifies candidate breast cancer susceptibility genes

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