Autores: Jacobs, K.B.; Yeager, M.; Zhou, W.; Wacholder, S.; Wang, Z.; Rodríguez-Santiago, B.; Hutchinson, A.; Deng, X.; Liu, C.; Horner, M.J.; Cullen, M.; Epstein, C.G.; Burdett, L.; Dean, M.C.; Chatterjee, N.; Samson, J.; Chung, C.C.; Kovaks, J.; Gapstur, S.M.; Stevens, V.L.; Teras, L.T.; Gaudet, M.M.; Albanes, D.; Weinstein, S.J.; Virtamo, J.; Taylor, P.R.; Freedman, N.D.; Abnet, C.C.; Goldstein, A.M.; Hu, N.; Yu, K.; Yuan, J.M.; Liao, L.; Ding, T.; Qiao, Y.L.; Gao, Y.T.; Koh, W.P.; Xiang, Y.B.; Tang, Z.Z.; Fan, J.H.; Aldrich, M.C.; Amos, C.; Blot, W.J.; Bock, C.H.; Gillanders, E.M.; Harris, C.C.; Haiman, C.A.; Henderson, B.E.; Kolonel, L.N.; Le Marchand, L.
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.