Detectable clonal mosaicism and its relationship to aging and cancer.

Authors:
Kevin B Jacobs Meredith Yeager Weiyin Zhou Sholom Wacholder Zhaoming Wang Benjamin Rodriguez-Santiago Amy Hutchinson Xiang Deng Chenwei Liu Marie-Josephe Horner Michael Cullen Caroline G Epstein Laurie Burdett Michael C Dean Nilanjan Chatterjee Joshua Sampson Charles C Chung Joseph Kovaks Susan M Gapstur Victoria L Stevens Lauren T Teras Mia M Gaudet Demetrius Albanes Stephanie J Weinstein Jarmo Virtamo Philip R Taylor Neal D Freedman Christian C Abnet Alisa M Goldstein Nan Hu Kai Yu Jian-Min Yuan Linda Liao Ti Ding You-Lin Qiao Yu-Tang Gao Woon-Puay Koh Yong-Bing Xiang Ze-Zhong Tang Jin-Hu Fan Melinda C Aldrich Christopher Amos William J Blot Cathryn H Bock Elizabeth M Gillanders Curtis C Harris Christopher A Haiman Brian E Henderson Laurence N Kolonel Loic Le Marchand Lorna H McNeill Benjamin A Rybicki Ann G Schwartz Lisa B Signorello Margaret R Spitz John K Wiencke Margaret Wrensch Xifeng Wu Krista A Zanetti Regina G Ziegler Jonine D Figueroa Montserrat Garcia-Closas Nuria Malats Gaelle Marenne Ludmila Prokunina-Olsson Dalsu Baris Molly Schwenn Alison Johnson Maria Teresa Landi Lynn Goldin Dario Consonni Pier Alberto Bertazzi Melissa Rotunno Preetha Rajaraman Ulrika Andersson Laura E Beane Freeman Christine D Berg Julie E Buring Mary A Butler Tania Carreon Maria Feychting Anders Ahlbom J Michael Gaziano Graham G Giles Goran Hallmans Susan E Hankinson Patricia Hartge Roger Henriksson Peter D Inskip Christoffer Johansen Annelie Landgren Roberta McKean-Cowdin Dominique S Michaud Beatrice S Melin Ulrike Peters Avima M Ruder Howard D Sesso Gianluca Severi Xiao-Ou Shu Kala Visvanathan Emily White Alicja Wolk Anne Zeleniuch-Jacquotte Wei Zheng Debra T Silverman Manolis Kogevinas Juan R Gonzalez Olaya Villa Donghui Li Eric J Duell Harvey A Risch Sara H Olson Charles Kooperberg Brian M Wolpin Li Jiao Manal Hassan William Wheeler Alan A Arslan H Bas Bueno-de-Mesquita Charles S Fuchs Steven Gallinger Myron D Gross Elizabeth A Holly Alison P Klein Andrea LaCroix Margaret T Mandelson Gloria Petersen Marie-Christine Boutron-Ruault Paige M Bracci Federico Canzian Kenneth Chang Michelle Cotterchio Edward L Giovannucci Michael Goggins Judith A Hoffman Bolton Mazda Jenab Kay-Tee Khaw Vittorio Krogh Robert C Kurtz Robert R McWilliams Julie B Mendelsohn Kari G Rabe Elio Riboli Anne Tjønneland Geoffrey S Tobias Dimitrios Trichopoulos Joanne W Elena Herbert Yu Laufey Amundadottir Rachael Z Stolzenberg-Solomon Peter Kraft Fredrick Schumacher Daniel Stram Sharon A Savage Lisa Mirabello Irene L Andrulis Jay S Wunder Ana Patiño García Luis Sierrasesúmaga Donald A Barkauskas Richard G Gorlick Mark Purdue Wong-Ho Chow Lee E Moore Kendra L Schwartz Faith G Davis Ann W Hsing Sonja I Berndt Amanda Black Nicolas Wentzensen Louise A Brinton Jolanta Lissowska Beata Peplonska Katherine A McGlynn Michael B Cook Barry I Graubard Christian P Kratz Mark H Greene Ralph L Erickson David J Hunter Gilles Thomas Robert N Hoover Francisco X Real Joseph F Fraumeni Neil E Caporaso Margaret Tucker Nathaniel Rothman Luis A Pérez-Jurado Stephen J Chanock

Nat Genet 2012 May 6;44(6):651-8. Epub 2012 May 6.

Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), Rockville, Maryland, USA.

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.

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http://dx.doi.org/10.1038/ng.2270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3372921PMC
May 2012
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