Confirmation of the reported association of clonal chromosomal mosaicism with an increased risk of incident hematologic cancer

Ursula M Schick; Andrew McDavid; Paul K Crane; Noah Weston; Kelly Ehrlich; Katherine M Newton; Robert Wallace; Ebony Bookman; Tabitha Harrison; Aaron Aragaki; David R Crosslin; Sophia S Wang; Alex P Reiner; Rebecca D Jackson; Ulrike Peters; Eric B Larson; Gail P Jarvik; Christopher S Carlson

doi:10.1371/journal.pone.0059823

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Confirmation of the reported association of clonal chromosomal mosaicism with an increased risk of incident hematologic cancer

Journal article

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Confirmation of the reported association of clonal chromosomal mosaicism with an increased risk of incident hematologic cancer

Ursula M Schick, Andrew McDavid, Paul K Crane, Noah Weston, Kelly Ehrlich, Katherine M Newton, Robert Wallace, Ebony Bookman, Tabitha Harrison, Aaron Aragaki, …

PloS one, Vol.8(3), pp.e59823-e59823

2013

DOI: 10.1371/journal.pone.0059823

PMCID: PMC3606281

PMID: 23533652

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Abstract

Chromosomal abnormalities provide clinical utility in the diagnosis and treatment of hematologic malignancies, and may be predictive of malignant transformation in individuals without apparent clinical presentation of a hematologic cancer. In an effort to confirm previous reports of an association between clonal mosaicism and incident hematologic cancer, we applied the anomDetectBAF algorithm to call chromosomal anomalies in genotype data from previously conducted Genome Wide Association Studies (GWAS). The genotypes were initially collected from DNA derived from peripheral blood of 12,176 participants in the Group Health electronic Medical Records and Genomics study (eMERGE) and the Women's Health Initiative (WHI). We detected clonal mosaicism in 169 individuals (1.4%) and large clonal mosaic events (>2 mb) in 117 (1.0%) individuals. Though only 9.5% of clonal mosaic carriers had an incident diagnosis of hematologic cancer (multiple myeloma, myelodysplastic syndrome, lymphoma, or leukemia), the carriers had a 5.5-fold increased risk (95% CI: 3.3-9.3; p-value = 7.5×10(-11)) of developing these cancers subsequently. Carriers of large mosaic anomalies showed particularly pronounced risk of subsequent leukemia (HR = 19.2, 95% CI: 8.9-41.6; p-value = 7.3×10(-14)). Thus we independently confirm the association between detectable clonal mosaicism and hematologic cancer found previously in two recent publications.

Aged

Chromosome Disorders - genetics

Female

Genetic Predisposition to Disease

Genome-Wide Association Study

Hematologic Neoplasms - genetics

Humans

Middle Aged

Mosaicism

Details

Title: Subtitle: Confirmation of the reported association of clonal chromosomal mosaicism with an increased risk of incident hematologic cancer
Creators: Ursula M Schick - Fred Hutch Cancer Center
Andrew McDavid - Fred Hutch Cancer Center
Paul K Crane - University of Washington
Noah Weston - Kaiser Permanente Washington Health Research Institute
Kelly Ehrlich - Kaiser Permanente Washington Health Research Institute
Katherine M Newton - University of Washington
Robert Wallace - University of Iowa
Ebony Bookman - National Human Genome Research Institute
Tabitha Harrison - Fred Hutch Cancer Center
Aaron Aragaki - Fred Hutch Cancer Center
David R Crosslin - University of Washington Medical Center
Sophia S Wang - Beckman Research Institute
Alex P Reiner
Rebecca D Jackson - The Ohio State University
Ulrike Peters - Fred Hutch Cancer Center
Eric B Larson - University of Washington
Gail P Jarvik - University of Washington Medical Center
Christopher S Carlson - University of Washington
Resource Type: Journal article
Publication Details: PloS one, Vol.8(3), pp.e59823-e59823
DOI: 10.1371/journal.pone.0059823
PMID: 23533652
PMCID: PMC3606281
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Grant note: N01WH42132 / WHI NIH HHS N01WH42114 / WHI NIH HHS N01WH32115 / WHI NIH HHS N01WH32102 / WHI NIH HHS N01WH24152 / WHI NIH HHS U01CKA137088 / PHS HHS N01WH42117 / WHI NIH HHS N01WH44221 / WHI NIH HHS N01WH32105 / WHI NIH HHS N01WH32118 / WHI NIH HHS N01WH42122 / WHI NIH HHS N01WH42130 / WHI NIH HHS U01AG06781 / NIA NIH HHS U01 HG006375 / NHGRI NIH HHS N01WH42112 / WHI NIH HHS N01WH42129 / WHI NIH HHS AG06781 / NIA NIH HHS N01WH32122 / WHI NIH HHS U01HG004438 / NHGRI NIH HHS HG004610 / NHGRI NIH HHS N01WH32113 / WHI NIH HHS P30 CA016056 / NCI NIH HHS N01WH42121 / WHI NIH HHS R25CA094880 / NCI NIH HHS N01WH42115 / WHI NIH HHS N01WH42124 / WHI NIH HHS U01 HG004610 / NHGRI NIH HHS U01 HG005152 / NHGRI NIH HHS U01 HG004424 / NHGRI NIH HHS N01WH42109 / WHI NIH HHS N01WH42123 / WHI NIH HHS N01WH32111 / WHI NIH HHS N01WH42118 / WHI NIH HHS N01WH42110 / WHI NIH HHS N01WH32106 / WHI NIH HHS R25 CA094880 / NCI NIH HHS N01WH32119 / WHI NIH HHS N01WH32101 / WHI NIH HHS N01WH42131 / WHI NIH HHS N01WH42108 / WHI NIH HHS N01WH42126 / WHI NIH HHS N01WH42113 / WHI NIH HHS N01WH32109 / WHI NIH HHS N01WH42107 / WHI NIH HHS N01WH42125 / WHI NIH HHS U01 HG005157 / NHGRI NIH HHS N01WH42116 / WHI NIH HHS N01WH32108 / WHI NIH HHS R01CKA059045 / PHS HHS U01 HG004438 / NHGRI NIH HHS N01WH32100 / WHI NIH HHS N01WH32112 / WHI NIH HHS N01WH42119 / WHI NIH HHS U01 AG006781 / NIA NIH HHS N01WH22110 / WHI NIH HHS N01WH42111 / WHI NIH HHS N01WH42120 / WHI NIH HHS
Language: English
Date published: 2013
Academic Unit: Epidemiology; Injury Prevention Research Center; Internal Medicine
Record Identifier: 9984363631802771

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