Identification of Two Genetic Loci Associated with Leukopenia after Chemotherapy in Patients with Breast Cancer.
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
02 08 2022
02 08 2022
Historique:
received:
09
12
2020
revised:
20
01
2022
accepted:
27
05
2022
pubmed:
3
6
2022
medline:
5
8
2022
entrez:
2
6
2022
Statut:
ppublish
Résumé
To identify molecular predictors of grade 3/4 neutropenic or leukopenic events (NLE) after chemotherapy using a genome-wide association study (GWAS). A GWAS was performed on patients in the phase III chemotherapy study SUCCESS-A (n = 3,322). Genotyping was done using the Illumina HumanOmniExpress-12v1 array. Findings were functionally validated with cell culture models and the genotypes and gene expression of possible causative genes were correlated with clinical treatment response and prognostic outcomes. One locus on chromosome 16 (rs4784750; NLRC5; P = 1.56E-8) and another locus on chromosome 13 (rs16972207; TNFSF13B; P = 3.42E-8) were identified at a genome-wide significance level. Functional validation revealed that expression of these two genes is altered by genotype-dependent and chemotherapy-dependent activity of two transcription factors. Genotypes also showed an association with disease-free survival in patients with an NLE. Two loci in NLRC5 and TNFSF13B are associated with NLEs. The involvement of the MHC I regulator NLRC5 implies the possible involvement of immuno-oncological pathways.
Identifiants
pubmed: 35653140
pii: 699313
doi: 10.1158/1078-0432.CCR-20-4774
pmc: PMC9357161
mid: NIHMS1814667
doi:
Substances chimiques
Intracellular Signaling Peptides and Proteins
0
NLRC5 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3342-3355Subventions
Organisme : NIGMS NIH HHS
ID : U19 GM061388
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004438
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA116201
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA015083
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG005137
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA196648
Pays : United States
Informations de copyright
©2022 American Association for Cancer Research.
Références
J Biol Chem. 2012 Jul 13;287(29):24294-303
pubmed: 22645137
Transpl Immunol. 2013 Mar;28(2-3):93-9
pubmed: 23353568
Cancer Discov. 2013 Jul;3(7):812-25
pubmed: 23764426
Arthritis Res Ther. 2011 Jul 06;13(4):227
pubmed: 21745420
Ann Oncol. 2013 Jun;24(6):1513-25
pubmed: 23396606
Protein Cell. 2013 Mar;4(3):168-75
pubmed: 23483478
Front Pharmacol. 2018 Mar 13;9:158
pubmed: 29593529
Annu Rev Immunol. 2003;21:231-64
pubmed: 12427767
Cell Death Differ. 2014 Jan;21(1):15-25
pubmed: 23787994
Cancer Res. 2008 Sep 1;68(17):7050-8
pubmed: 18757419
Nat Genet. 2013 Oct;45(10):1238-1243
pubmed: 24013639
Curr Opin Hematol. 2015 Jan;22(1):67-73
pubmed: 25402621
Eur J Cancer. 2011 Jan;47(1):8-32
pubmed: 21095116
J Med Chem. 1987 Feb;30(2):395-9
pubmed: 3806619
Pharmacogenet Genomics. 2011 Sep;21(9):552-8
pubmed: 21799462
Clin Breast Cancer. 2005 Aug;6(3):260-6; discussion 267-9
pubmed: 16137438
Drug Metab Dispos. 2019 Sep;47(9):983-994
pubmed: 31292129
Curr Opin Immunol. 2004 Feb;16(1):67-75
pubmed: 14734112
J Immunol. 2012 Apr 15;188(8):3820-8
pubmed: 22412192
Lancet Oncol. 2007 Dec;8(12):1071-1078
pubmed: 18024211
Pharmacogenomics. 2008 Nov;9(11):1695-709
pubmed: 19018724
Support Care Cancer. 2006 Sep;14(9):901-9
pubmed: 16622653
Proc Natl Acad Sci U S A. 2016 May 24;113(21):5999-6004
pubmed: 27162338
Immunity. 2015 Nov 17;43(5):923-32
pubmed: 26572062
Breast Cancer Res Treat. 2012 Apr;132(3):947-53
pubmed: 21706156
PLoS Genet. 2015 Mar 26;11(3):e1005088
pubmed: 25811463
Oncotarget. 2017 May 9;8(44):78133-78143
pubmed: 29100455
JAMA Oncol. 2019 Aug 01;5(8):1205-1214
pubmed: 30973611
Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13794-9
pubmed: 20639463
Curr Med Chem. 2012;19(12):1792-803
pubmed: 22414087
J Natl Cancer Inst. 2014 May 15;106(5):
pubmed: 24832787
Cancer Cell. 2009 Sep 8;16(3):259-66
pubmed: 19732725
Int J Epidemiol. 2012 Feb;41(1):273-86
pubmed: 22253303
Genet Epidemiol. 2010 Sep;34(6):591-602
pubmed: 20718045
Oncoimmunology. 2016 Mar 28;5(6):e1151593
pubmed: 27471621
J Exp Med. 2007 Aug 6;204(8):1959-71
pubmed: 17664289
J Immunother Cancer. 2016 Jul 19;4:39
pubmed: 27437103
Mol Psychiatry. 2021 Dec;26(12):7454-7464
pubmed: 34535768
Crit Rev Oncol Hematol. 2014 Jun;90(3):190-9
pubmed: 24434034
Haematologica. 2007 Feb;92(2):e20-3
pubmed: 17405749
Clin Cancer Res. 2006 Aug 1;12(15):4533-44
pubmed: 16899599
J Natl Cancer Inst. 2003 Oct 15;95(20):1545-8
pubmed: 14559877
BMC Cancer. 2014 Mar 19;14:201
pubmed: 24641830
Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9440-5
pubmed: 12883005
Hum Mol Genet. 2013 May 15;22(10):2119-27
pubmed: 23314186
J Interferon Cytokine Res. 2013 Oct;33(10):588-96
pubmed: 23705899
Breast Cancer Res. 2020 Oct 23;22(1):111
pubmed: 33097092
Cell. 2010 Apr 30;141(3):483-96
pubmed: 20434986
Cell Res. 2012 May;22(5):836-47
pubmed: 22491475
Biochim Biophys Acta Mol Cell Res. 2017 Jan;1864(1):51-61
pubmed: 27741412
Biofactors. 2016 Jul 8;42(4):349-57
pubmed: 27087581
Breast Care (Basel). 2018 Mar;13(1):8-14
pubmed: 29950961
Nat Rev Immunol. 2009 Jul;9(7):491-502
pubmed: 19521398
Lancet. 2015 May 9;385(9980):1863-72
pubmed: 25740286
Semin Immunol. 2006 Oct;18(5):284-9
pubmed: 16931039
J Thorac Oncol. 2011 Nov;6(11):1881-8
pubmed: 21841503