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Detectable clonal mosaicism and its relationship to aging and cancer.

Authors
Jacobs-KB; Yeager-M; Zhou-W; Wacholder-S; Wang-Z; Rodriguez-Santiago-B; Hutchinson-A; Deng-X; Liu-C; Horner-MJ; Cullen-M; Epstein-CG; Burdett-L; Dean-MC; Chatterjee-N; Sampson-J; Chung-CC; Kovaks-J; Gapstur-SM; Stevens-VL; Teras-LT; Gaudet-MM; Albanes-D; Weinstein-SJ; Virtamo-J; Taylor-PR; Freedman-ND; Abnet-CC; Goldstein-AM; Hu-N; Yu-K; Yuan-JM; Liao-L; Ding-T; Qiao-YL; Gao-YT; Koh-WP; Xiang-YB; Tang-ZZ; Fan-JH; Aldrich-MC; Amos-C; Blot-WJ; Bock-CH; Gillanders-EM; Harris-CC; Haiman-CA; Henderson-BE; Kolonel-LN; Le Marchand-L; McNeill-LH; Rybicki-BA; Schwartz-AG; Signorello-LB; Spitz-MR; Wiencke-JK; Wrensch-M; Wu-X; Zanetti-KA; Ziegler-RG; Figueroa-JD; Garcia-Closas-M; Malats-N; Marenne-G; Prokunina-Olsson-L; Baris-D; Schwenn-M; Johnson-A; Landi-MT; Goldin-L; Consonni-D; Bertazzi-PA; Rotunno-M; Rajaraman-P; Andersson-U; Freeman-LE; Berg-CD; Buring-JE; Butler-MA; Carreon-T; Feychting-M; Ahlbom-A; Gaziano-JM; Giles-GG; Hallmans-G; Hankinson-SE; Hartge-P; Henriksson-R; Inskip-PD; Johansen-C; Landgren-A; McKean-Cowdin-R; Michaud-DS; Melin-BS; Peters-U; Ruder-AM; Sesso-HD; Severi-G; Shu-XO; Visvanathan-K; White-E; Wolk-A; Zeleniuch-Jacquotte-A; Zheng-W; Silverman-DT; Kogevinas-M; Gonzalez-JR; Villa-O; Li-D; Duell-EJ; Risch-HA; Olson-SH; Kooperberg-C; Wolpin-BM; Jiao-L; Hassan-M; Wheeler-W; Arslan-AA; Bueno-de-Mesquita-HB; Fuchs-CS; Gallinger-S; Gross-MD; Holly-EA; Klein-AP; Lacroix-A; Mandelson-MT; Petersen-G; Boutron-Ruault-MC; Bracci-PM; Canzian-F; Chang-K; Cotterchio-M; Giovannucci-EL; Goggins-M; Bolton-JA; Jenab-M; Khaw-KT; Krogh-V; Kurtz-RC; McWilliams-RR; Mendelsohn-JB; Rabe-KG; Riboli-E; Tjřnneland-A; Tobias-GS; Trichopoulos-D; Elena-JW; Yu-H; Amundadottir-L; Stolzenberg-Solomon-RZ; Kraft-P; Schumacher-F; Stram-D; Savage-SA; Mirabello-L; Andrulis-IL; Wunder-JS; García-AP; Sierrasesúmaga-L; Barkauskas-DA; Gorlick-RG; Purdue-M; Chow-WH; Moore-LE; Schwartz-KL; Davis-FG; Hsing-AW; Berndt-SI; Black-A; Wentzensen-N; Brinton-LA; Lissowska-J; Peplonska-B; McGlynn-KA; Cook-MB; Graubard-BI; Kratz-CP; Greene-MH; Erickson-RL; Hunter-DJ; Thomas-G; Hoover-RN; Real-FX; Fraumeni-JF Jr.; Caporaso-NE; Tucker-M; Rothman-N; Pérez-Jurado-LA; Chanock-SJ
Source
Nat Genet 2012 Jun; 44(6):651-658
NIOSHTIC No.
20040807
Abstract
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.
Keywords
Cell-biology; Cell-function; Genetics; Genetic-factors; Genes; Chromosome-disorders; Blood-cells; Cancer; Humans; Men; Women; Age-factors
CODEN
NGENEC
Publication Date
20120601
Document Type
Journal Article
Email Address
chanocks@mail.nih.gov
Fiscal Year
2012
NTIS Accession No.
NTIS Price
Identifying No.
B06062012
Issue of Publication
6
ISSN
1061-4036
NIOSH Division
DSHEFS; DART
Source Name
Nature Genetics
State
MD; GA; MN; PA; TN; TX; MI; CA; HI; VT; MA; RI
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