Refining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions

被引：0

作者：

Jia, Guochong ^{[1
]}

Chen, Zhishan ^{[1
]}

Ping, Jie ^{[1
]}

Cai, Qiuyin ^{[1
]}

Tao, Ran ^{[2
]}

Li, Chao ^{[1
]}

Bauer, Joshua A. ^{[3
]}

Xie, Yuhan ^{[4
]}

Ambs, Stefan ^{[5
]}

Barnard, Mollie E. ^{[6
]}

Chen, Yu ^{[7
]}

Choi, Ji-Yeob ^{[8
,9
]}

Gao, Yu-Tang ^{[10
,11
]}

Garcia-Closas, Montserrat ^{[12
]}

Gu, Jian ^{[13
]}

Hu, Jennifer J. ^{[14
]}

Iwasaki, Motoki ^{[15
]}

John, Esther M. ^{[16
,17
]}

Kweon, Sun-Seog ^{[18
,19
]}

Li, Christopher I. ^{[20
]}

Matsuda, Koichi ^{[21
]}

Matsuo, Keitaro ^{[22
,23
]}

Nathanson, Katherine L. ^{[24
,25
]}

Nemesure, Barbara ^{[26
]}

Olopade, Olufunmilayo I. ^{[27
]}

Pal, Tuya ^{[28
]}

Park, Sue K. ^{[9
,29
,30
]}

Park, Boyoung ^{[31
]}

Press, Michael F. ^{[32
]}

Sanderson, Maureen ^{[33
]}

Sandler, Dale P. ^{[34
]}

Shen, Chen-Yang ^{[35
,36
]}

Troester, Melissa A. ^{[37
]}

Yao, Song ^{[38
]}

Zheng, Ying ^{[39
]}

Ahearn, Thomas ^{[12
]}

Brewster, Abenaa M. ^{[40
]}

Falusi, Adeyinka ^{[41
]}

Hennis, Anselm J. M. ^{[26
,42
]}

Ito, Hidemi ^{[43
,44
]}

Kubo, Michiaki ^{[45
]}

Lee, Eun-Sook ^{[46
,47
]}

Makumbi, Timothy ^{[48
]}

Ndom, Paul ^{[49
]}

Noh, Dong-Young ^{[50
,51
]}

O'Brien, Katie M. ^{[34
]}

Ojengbede, Oladosu ^{[52
]}

Olshan, Andrew F. ^{[37
]}

Park, Min-Ho ^{[53
]}

Reid, Sonya ^{[54
]}

机构：

[1] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr, Med Ctr,Dept Med,Div Epidemiol, Nashville, TN 37235 USA

[2] Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN USA

[3] Vanderbilt Univ, Sch Med, Vanderbilt Inst Chem Biol, Dept Biochem, Nashville, TN 37240 USA

[4] Yale Sch Publ Hlth, Dept Biostat, New Haven, CT USA

[5] NCI, Ctr Canc Res, Lab Human Carcinogenesis, NIH, Bethesda, MD USA

[6] Boston Univ, Slone Epidemiol Ctr, Boston, MA USA

[7] NYU Grossman Sch Med, Dept Populat Hlth, Div Biostat, New York, NY USA

[8] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul, South Korea

[9] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea

[10] Shanghai Jiaotong Univ Sch Med, Shanghai Canc Inst, Renji Hosp, State Key Lab Oncogene & Related Genes, Shanghai, Peoples R China

[11] Shanghai Jiao Tong Univ, Renji Hosp, Shanghai Canc Inst, Sch Med,Dept Epidemiol, Shanghai, Peoples R China

[12] NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA

[13] Univ Texas, Md Anderson Canc Ctr, Houston, TX USA

[14] Univ Miami, Sch Med, Dept Publ Hlth Sci, Miami, FL USA

[15] Natl Canc Ctr, Inst Canc Control, Div Epidemiol, Tokyo, Japan

[16] Stanford Univ, Sch Med, Dept Epidemiol & Populat Hlth, Stanford, CA USA

[17] Stanford Univ, Sch Med, Dept Med, Stanford, CA USA

[18] Chonnam Natl Univ, Med Sch, Dept Prevent Med, Hwasun, South Korea

[19] Chonnam Natl Univ, Hwasun Hosp, Jeonnam Reg Canc Ctr, Hwasun, South Korea

[20] Fred Hutchinson Canc Ctr, Div Publ Hlth Sci, Seattle, WA USA

[21] Univ Tokyo, Grad Sch Frontier Sci, Lab Clin Genome Sequencing, Tokyo, Japan

[22] Aichi Canc Ctr Res Inst, Div Canc Epidemiol & Prevent, Nagoya, Japan

[23] Nagoya Univ, Grad Sch Med, Div Canc Epidemiol, Nagoya, Japan

[24] Univ Penn, Perelman Sch Med, Dept Med, Div Hematol Oncol, Philadelphia, PA USA

[25] Univ Penn, Perelman Sch Med, Basser Ctr BRCA, Abramson Canc Ctr, Philadelphia, PA USA

[26] SUNY Stony Brook, Renaissance Sch Med, Dept Family Populat & Prevent Med, Stony Brook, NY USA

[27] Univ Chicago, Dept Med, Ctr Clin Canc Genet & Global Hlth, Chicago, IL USA

[28] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr Dept Med, Med Ctr, Dept Med,Div Genet Med, Nashville, TN 37232 USA

[29] Seoul Natl Univ, Coll Med, Integrated Major Innovat Med Sci, Seoul, South Korea

[30] Seoul Natl Univ, Canc Res Inst, Seoul, South Korea

[31] Hanyang Univ, Coll Med, Dept Prevent Med, Seoul, South Korea

[32] Univ Southern Calif, Norris Comprehens Canc Ctr, Dept Pathol, Los Angeles, CA USA

[33] Meharry Med Coll, Dept Family & Community Med, Nashville, TN USA

[34] Natl Inst Environm Hlth Sci, NIH, Epidemiol Branch, Res Triangle Pk, NC USA

[35] China Med Univ, Coll Publ Hlth, Taichong, Taiwan

[36] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan

[37] Univ North Carolina Chapel Hill, Lineberger Comprehens Canc Ctr, Dept Epidemiol, Chapel Hill, NC USA

[38] Roswell Pk Comprehens Canc Ctr, Dept Canc Prevent & Control, Buffalo, NY USA

[39] Shanghai Municipal Ctr Dis Control & Prevent, Shanghai, Peoples R China

[40] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX USA

[41] Univ Ibadan, Inst Adv Med Res & Training, Coll Med, Genet & Bioeth Res Unit, Ibadan, Nigeria

[42] Univ West Indies, George Alleyne Chron Dis Res Ctr, Bridgetown, Barbados

[43] Aichi Canc Ctr Res Inst, Div Canc Informat & Control, Nagoya, Japan

[44] Nagoya Univ, Grad Sch Med, Dept Descript Canc Epidemiol, Nagoya, Japan

[45] RIKEN Ctr Integrat Med Sci, Yokohama, Japan

[46] Natl Canc Ctr, Grad Sch Canc Sci & Policy, Goyang, South Korea

[47] Natl Canc Ctr, Hosp, Goyang, Gyeonggi, South Korea

[48] Mulago Hosp, Dept Surg, Kampala, Uganda

[49] Yaounde Gen Hosp, Yaounde, Cameroon

[50] Seoul Natl Univ, Canc Res Inst, Coll Med, Seoul, South Korea

来源：

NATURE GENETICS | 2025年 / 57卷 / 01期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; IDENTIFIES; VARIANTS; EXPRESSION; ENHANCERS; DATABASE; WOMEN; EQTL;

D O I：

10.1038/s41588-024-02031-y

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant. Analyses integrating functional genomics data identified 195 putative susceptibility genes, enriched in PI3K/AKT, TNF/NF-kappa B, p53 and Wnt/beta-catenin pathways. Single-cell RNA sequencing or in vitro experiment data provided additional functional evidence for 105 genes. Our study uncovered large numbers of association signals and candidate susceptibility genes for breast cancer, uncovered breast cancer genetics and biology, and supported the value of including multi-ancestry data in fine-mapping analyses.

引用

页码：80 / 87

页数：17

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