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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; Tjønneland 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
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
Page last reviewed: March 25, 2022
Content source: National Institute for Occupational Safety and Health Education and Information Division