ArticleJournal of the National Cancer Institute2016
BRCA2 Polymorphic Stop Codon K3326X and the Risk of Breast, Prostate, and Ovarian Cancers.
Huong D Meeks, Honglin Song, Kyriaki Michailidou, Manjeet K Bolla, Joe Dennis, Qin Wang, Daniel Barrowdale, Debra Frost, EMBRACE, Lesley McGuffog and 250 more
Article in Journal of the National Cancer Institute, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 1 pooled it
9.1field-weighted citation impact, top 2% of its field
1 · What the graph read from it
What it found
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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
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
PRostate cancer AssoCiation group To Investigate Cancer Associated aLterations in the genome
Antonis C Antoniou
Andrew Berchuck
Anthony Swerdlow
Georgia Chenevix-Trench
Alison M Dunning
Paul D P Pharoah
Per Hall
Douglas F Easton
Fergus J Couch
Amanda B Spurdle
David E Goldgar
QIMR Berghofer Medical Research Institute · AUUniversity of Cambridge · GBThe Netherlands Cancer Institute · NLThe University of Melbourne · AUPeter MacCallum Cancer Centre · AUGerman Cancer Research Center · DEHeidelberg University · DEUniversity of Utah · USBreast Cancer Research Foundation · USCancer Council Victoria · AUCentre for Human Genetics · GBGuy's Hospital · GBImperial College London · GBRoyal Marsden NHS Foundation Trust · GBUniversity of California, Los Angeles · USBorstkankervereniging Nederland · NLComprehensive Cancer Center Erlangen · DELondon Women's Clinic · GB
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
NRG Oncology Network Group Operations Center - GY9 BIQSFP Reports/BudgetsU10CA180868 · NCI · NRG ONCOLOGY FOUNDATION, INC. · PI NORMAN WOLMARK · 2014 to 2026
$206.8M
Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3M
NRG Oncology NCORP Research Base-BIQSFPUG1CA189867 · NCI · NRG ONCOLOGY FOUNDATION, INC. · PI Deborah Watkins Bruner, Lisa A. Kachnic · 2014 to 2026
$140.5M
WORD PROCESSING CENTER--COREP30CA006927 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI Margaret von Mehren · 1985 to 2026
$138.8M
Clinical Genetic Studies of Familial and Hereditary Cancer SyndromesZIACP010144 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI SAVAGE, SHARON A. · 2009 to 2025
$111.8M
The Role of CHFR in Tumorigenesis and Paclitaxel-Sensitivity in Breast CancerP50CA116201 · NCI · MAYO CLINIC ROCHESTER · PI PETER C LUCAS · 2005 to 2026
$49.9M
Epidemiologic StudiesU19CA148065 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI AHSAN, HABIBUL, BRUGGE, JOAN SIEFERT · 2010 to 2014
$10.6M
Epidemiological and Clinical Translational Studies Post Genome-Wide AssociationU19CA148537 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI EASTON, DOUGLAS FREDERICK, EELES, ROSALIND · 2010 to 2014
$10.4M
Ovarian cancer GWAS discovery, expansion and replication (N2 - Project #1)U19CA148112 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI SELLERS, THOMAS A · 2010 to 2014
$10.2M
A genome-wide association study for breast cancer in BRCA1 mutation carriersR01CA128978 · NCI · MAYO CLINIC ROCHESTER · PI COUCH, FERGUS JOSEPH · 2008 to 2012
$4.8M
Identifying and validating novel susceptibility genes for breast cancerR01CA176785 · NCI · MAYO CLINIC ROCHESTER · PI COUCH, FERGUS JOSEPH, NATHANSON, KATHERINE L. · 2014 to 2018
$3.4M
Cancer Research UK 10119Cancer Research UK 10124Cancer Research UK 11174Cancer Research UK 16459Cancer Research UK 16561Cancer Research UK 16563Cancer Research UK 16565Cancer Research UK 17523Cancer Research UK 19170Cancer Research UK C12292/A11174Cancer Research UK C1287/A10118Cancer Research UK C1287/A12014Medical Research Council MR/N005813/1NCI NIH HHS CA128978NCI NIH HHS P30 CA006927NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA015083NCI NIH HHS P50 CA116201NCI NIH HHS R01 CA116167NCI NIH HHS R01 CA128978NCI NIH HHS R01 CA176785NCI NIH HHS U01 CA116167NCI NIH HHS U10 CA180868NCI NIH HHS U19 CA148065NCI NIH HHS U19 CA148112NCI NIH HHS U19-CA148112NCI NIH HHS U19 CA148537NCI NIH HHS UG1 CA189867
6 · The paper itself
Abstract
backgroundThe K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers.
methodsUsing weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided.
resultsThe K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10(-) (6)) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10(-3)). These associations were stronger for serous ovarian cancer and for estrogen receptor-negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10(-5) and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10(-5), respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed.
conclusionsOur study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations.
Indexed as
Codon, TerminatorPolymorphism, Single NucleotideAdultAgedBRCA2 ProteinBreast NeoplasmsFemaleGenetic Predisposition to DiseaseHeterozygoteHumansLogistic ModelsLysineMaleMiddle AgedNeoplasm InvasivenessOdds RatioBRCA2 ProteinBRCA2 protein, humanCodon, TerminatorLysine
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.
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