Detectable clonal mosaicism and its relationship to aging and cancer

Details

• Personal Author:
  Abnet CC ; Ahlbom A ; Albanes D ; Aldrich MC ; Amos C ; Andersson U ; Baris D ; Berg CD ; Bertazzi, Pier A. ; Blot WJ ; Bock CH ; Burdett L ; Buring JE ; Butler MA ; Carreon T ; Chatterjee N ; Chung CC ; Consonni D ; Cullen M ; Dean MC ; Deng X ; Ding T ; Epstein CG ; Fan JH ; Feychting M ; Figueroa JD ; Freedman ND ; Freeman LE ; Gao YT ; Gapstur SM ; Garcia-Closas M ; Gaudet MM ; Gillanders EM ; Goldin L ; Goldstein AM ; Haiman CA ; Harris CC ; Henderson BE ; Horner MJ ; Hu N ; Hutchinson A ; Jacobs KB ; Johnson A ; Koh WP ; Kolonel LN ; Kovaks J ; Landi MT ; Le Marchand L ; Liao L ; Liu C ; Malats N ; Marenne G ; McNeill LH ; Prokunina-Olsson L ; Qiao YL ; Rajaraman P ; Rodriguez-Santiago B ; Rotunno M ; Rybicki BA ; Sampson J ; Schwartz AG ; Schwenn M ; Signorello LB ; Spitz MR ; Stevens VL ; Tang ZZ ; Taylor, Philip R. ; Teras LT ; Virtamo J ; Wacholder S ; Wang Z ; Weinstein SJ ; Wiencke JK ; Wrensch M ; Wu X ; Xiang YB ; Yeager M ; Yu K ; Yuan JM ; Zanetti KA ; Zhou W ; Ziegler RG
• Description:
  In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10-8). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10-11). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases. [Description provided by NIOSH]
• Subjects:
  Age Factors Blood Chromosomes Genetics Men Neoplasms Occupational Health Safety Women
• Keywords:
  Age-factors Blood-cells Cancer Cell-biology Cell-function Chromosome-disorders Genes Genetic-factors Humans
• ISSN:
  1061-4036
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  California ; Georgia ; Hawaii ; Maryland ; Massachusetts ; Michigan ; Minnesota ; OSHA Region 1 ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 5 ; OSHA Region 6 ; OSHA Region 9 ; Pennsylvania ; Rhode Island ; Tennessee ; Texas ; Vermont
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DSHEFS - Division of Surveillance, Hazard Evaluations, and Field Studies ; DART - Division of Applied Research and Technology
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  44
• Issue:
  6
• NIOSHTIC Number:
  nn:20040807
• Citation:
  Nat Genet 2012 Jun; 44(6):651-658
• Email:
  chanocks@mail.nih.gov
• Federal Fiscal Year:
  2012
• Peer Reviewed:
  True
• Source Full Name:
  Nature Genetics
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f0e616a29f216e4f55f59f14cc6bc339de54c3aa46c2af9fead16e5da2814a246c546371fa3c5214a281b9dbe2045d3a2d78b03616557bb2add75f484e82797f
• Download URL:
  https://stacks.cdc.gov/view/cdc/193539/cdc_193539_DS1.pdf
• File Type:
  [PDF - 1.08 MB ]