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Detectable clonal mosaicism and its relationship to aging and cancer.
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2012 (English)In: Nature Genetics, ISSN 1061-4036, Vol. 44, no 6, 651-658 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
New York: Nature Publishing Group, 2012. Vol. 44, no 6, 651-658 p.
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Medical Genetics
URN: urn:nbn:se:umu:diva-55639DOI: 10.1038/ng.2270ISI: 000304551100011PubMedID: 22561519OAI: diva2:528494
Available from: 2012-05-25 Created: 2012-05-25 Last updated: 2015-04-22Bibliographically approved

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Andersson, UlrikaHallmans, GöranHenriksson, RogerMelin, Beatrice S
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