Evidence map›Paper›PMID 40288678›Full record

ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2025

Association of gene variant type and location with breast cancer risk in the general population.

M P Akamandisa, N J Boddicker, S Yadav, C Hu, S N Hart, C B Ambrosone, H Anton-Culver, P L Auer, C Bodelon, E S Burnside and 35 more

Abstract read
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Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Inherited cancer syndromes in adult oncology: a referral guide based on malignant tumor and polyp features.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

45 authors.

M P AkamandisaDivision of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA.
N J BoddickerDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, USA.
S YadavDepartment of Oncology, Mayo Clinic, Rochester, USA.
C HuDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, USA.
S N HartDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, USA.
C B AmbrosoneDepartment of Cancer Prevention and Control, Roswell Park Cancer Center, Buffalo, USA.
H Anton-CulverUniversity of California Irvine, Irvine, USA.
P L AuerDivision of Biostatistics, Institute for Health & Equity, and Cancer Center, Medical College of Wisconsin, Milwaukee, USA.
C BodelonDepartment of Population Science, American Cancer Society, Atlanta, USA.
E S BurnsideDepartment of Radiology, University of Wisconsin, Madison, USA.
F ChenKeck School of Medicine, University of Southern California, Los Angeles, USA.
A H EliassenHarvard TH Chan School of Public Health, Harvard University, Cambridge, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston.
D E GoldgarUniversity of Utah, Salt Lake, USA.
C HaimanKeck School of Medicine, University of Southern California, Los Angeles, USA.
J M HodgeDepartment of Population Science, American Cancer Society, Atlanta, USA.
H HuangHarvard TH Chan School of Public Health, Harvard University, Cambridge, USA.
E M JohnDepartment of Epidemiology and Population Health, Stanford University School of Medicine, Palo Alto, USA.
R KaramAmbry Genetics, Aliso Viejo, USA.
J V LaceyBeckman Research Institute, City of Hope Cancer Center, Duarte, USA.
S LindstroemDepartment of Epidemiology, University of Washington, Seattle, USA.
M E MartinezDepartment of Family Medicine and Public Health, University of California San Diego, San Dieg, USA.
J NaDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, USA.
S L NeuhausenBeckman Research Institute, City of Hope Cancer Center, Duarte, USA.
K M O'BrienNational Institute of Environmental Health Sciences, Durham, USA.
J E OlsonDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, USA.
T PalDivision of Genetic Medicine in the Department of Medicine, Vanderbilt University Medical Center, Nashville, USA.
J R PalmerSlone Epidemiology Center, Boston University, Boston, USA.
A V PatelDepartment of Population Science, American Cancer Society, Atlanta, USA.
T PesaranAmbry Genetics, Aliso Viejo, USA.
E C PolleyDepartment of Public Health Sciences, University of Chicago, Chicago, USA.
M E RichardsonAmbry Genetics, Aliso Viejo, USA.
K J RuddyDepartment of Oncology, Mayo Clinic, Rochester, USA.
D P SandlerNational Institute of Environmental Health Sciences, Durham, USA.
L R TerasDepartment of Population Science, American Cancer Society, Atlanta, USA.
A Trentham-DietzUniversity of Wisconsin-Madison School of Medicine and Public Health, Madison, USA.
C M VachonDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, USA.
C WeinbergBiostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Durham.
S J WinhamDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, USA.
S YaoDepartment of Cancer Prevention and Control, Roswell Park Cancer Center, Buffalo, USA.
G ZirpoliSlone Epidemiology Center, Boston University, Boston, USA.
P KraftTrans-Divisional Research Program, National Cancer Institute, Rockville, USA.
J N WeitzelThe University of Kansas Cancer Center, Kansas City, USA.
S M DomchekBasser Center for BRCA, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA; Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA.
F J CouchDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, USA.
K L NathansonDivision of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA; Basser Center for BRCA, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA. Electronic address: knathans@upenn.edu.

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Christian Capitini · 1985 to 2026
$142.6M
Statistical MethodsP01CA087969 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ROSNER, BERNARD A · 2000 to 2019
$77.8M
WOMEN'S HEALTH INITIATIVE - CLINICAL COORDINATING CENTER: TASK AREA B - LONG LIFE STUDY VISIT 2 LIMITED HOME VISIT75N92021D00001 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ANDERSON, GARNET L. · 2021 to 2025
$52.0M
The Role of CHFR in Tumorigenesis and Paclitaxel-Sensitivity in Breast CancerP50CA116201 · NCI · MAYO CLINIC ROCHESTER · PI Fergus Joseph Couch · 2005 to 2026
$49.9M
The Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4M
A Follow-up Study for Causes of Cancer in Black WomenU01CA164974 · NCI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Kimberly A. Bertrand, Yvette C Cozier · 2017 to 2026
$24.0M
Long Term Multidisciplinary Study of Cancer in Women: The Nurses Health StudyUM1CA186107 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, STAMPFER, MEIR · 2014 to 2023
$22.3M
Paul Calabresi Program in Clinical/Translational Research at Mayo ClinicK12CA090628 · NCI · MAYO CLINIC ROCHESTER · PI WEROHA, SARAVUT · 2001 to 2025
$19.7M
Life Course Cancer Epidemiology Cohort in WomenUM1CA176726 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI WILLETT, WALTER C. · 2013 to 2017
$15.7M
Breast Cancer genetic study in African-ancestry populationsR01CA202981 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Wei Zheng · 2016 to 2026
$14.1M
Epidemiologic StudiesU19CA148065 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI AHSAN, HABIBUL, BRUGGE, JOAN SIEFERT · 2010 to 2014
$10.6M
The Two Sister StudyZIAES102245 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI WEINBERG, CLARICE · 2009 to 2025
$8.6M
Intramural NIH HHS Z01 ES044005Intramural NIH HHS Z01 ES049033Intramural NIH HHS ZIA ES102245NCATS NIH HHS UL1 TR000445NCI NIH HHS K12 CA090628NCI NIH HHS P01 CA087969NCI NIH HHS P30 CA014520NCI NIH HHS P50 CA116201NCI NIH HHS R01 CA097396NCI NIH HHS R01 CA098663NCI NIH HHS R01 CA140286NCI NIH HHS R01 CA192393NCI NIH HHS R01 CA202981NCI NIH HHS R01 CA225662NCI NIH HHS R35 CA253187NCI NIH HHS U01 CA164974NCI NIH HHS U19 CA148065NCI NIH HHS UM1 CA176726NCI NIH HHS UM1 CA186107NHLBI NIH HHS 75N92021D00001NHLBI NIH HHS 75N92021D00002WHI NIH HHS 75N92021D00003WHI NIH HHS 75N92021D00004WHI NIH HHS 75N92021D00005
6 · The paper itself

Abstract

backgroundPathogenic variants (PVs) in ATM, BRCA1, BRCA2, CHEK2, and PALB2 are associated with increased breast cancer risk. It is unknown, however, whether this risk differs by PV type or location in carriers ascertained from the general population. PATIENTS AND

methodsTo evaluate breast cancer risks associated with PV type and location in ATM, BRCA1, BRCA2, CHEK2, and PALB2, we carried out age-adjusted case-control association analysis in 32 247 women with and 32 544 age-matched women without breast cancer from the CARRIERS Consortium. PVs were grouped by type and location within genes and assessed for risks of breast cancer [odds ratios (OR), 95% confidence intervals (CI), and P values] using logistic regression.

resultsCompared with women carrying BRCA2 exon 11 protein truncating variants (PTVs) in the CARRIERS population-based study, women with BRCA2 ex1-10 PTVs (OR = 13.5, 95% CI 6.0-38.7, P < 0.001) and ex13-27 PTVs (OR = 9.0, 95% CI 4.9-18.5, P < 0.001) had higher breast cancer risks, lower rates of estrogen receptor (ER)-negative breast cancer (ex13-27 OR = 0.5, 95% CI 0.2-0.9, P = 0.035; ex1-10 OR = 0.5, 95% CI 0.1-1.0, P = 0.065), and earlier age at breast cancer diagnosis (ex13-27 5.5 years, P < 0.001; ex1-10 2.4 years, P = 0.169). These associations with ER-negative breast cancer and age were replicated in a high-risk clinical cohort from Ambry Genetics and the population-based UK Biobank cohort. No differences in risk by gene region were observed for PTVs in other predisposition genes.

conclusionsPopulation-based and clinical high-risk cohorts establish that PTVs in exon 11 of BRCA2 are associated with reduced breast cancer risk, later age at diagnosis, and greater risk of ER-negative disease. These differential risks may improve individualized risk prediction and clinical management for women carrying BRCA2 PTVs.

Indexed as

Breast NeoplasmsGenetic Predisposition to DiseaseAdultAgedAtaxia Telangiectasia Mutated ProteinsBRCA1 ProteinBRCA2 ProteinCase-Control StudiesCheckpoint Kinase 2Fanconi Anemia Complementation Group N ProteinFemaleHumansMiddle AgedRisk FactorsAtaxia Telangiectasia Mutated ProteinsATM protein, humanBRCA1 ProteinBRCA1 protein, humanBRCA2 ProteinBRCA2 protein, humanCheckpoint Kinase 2CHEK2 protein, humanFanconi Anemia Complementation Group N ProteinPALB2 protein, humanbreast cancer riskpathogenic variant type and locationpopulation-based cohort

Identifiers

PMID40288678
PMCPMC12288856

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