Detectable clonal mosaicism and its relationship to aging and cancer

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

doi:10.1038/ng.2270

Detectable clonal mosaicism and its relationship to aging and cancer

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 StevensLauren 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

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.

Originalsprog	Engelsk
Tidsskrift	Nature Genetics
Vol/bind	44
Udgave nummer	6
Sider (fra-til)	651-8
Antal sider	8
ISSN	1061-4036
DOI	https://doi.org/10.1038/ng.2270
Status	Udgivet - 6 maj 2012
Udgivet eksternt	Ja

Adgang til dokumentet

10.1038/ng.2270

Citationsformater

Jacobs, K. B., Yeager, M., Zhou, W., Wacholder, S., Wang, Z., Rodriguez-Santiago, B., Hutchinson, A., Deng, X., Liu, C., Horner, M.-J., Cullen, M., Epstein, C. G., Burdett, L., Dean, M. C., Chatterjee, N., Sampson, J., Chung, C. C., Kovaks, J., Gapstur, S. M., ... Chanock, S. J. (2012). Detectable clonal mosaicism and its relationship to aging and cancer. Nature Genetics, 44(6), 651-8. https://doi.org/10.1038/ng.2270

Jacobs, KB, Yeager, M, Zhou, W, Wacholder, S, Wang, Z, Rodriguez-Santiago, B, Hutchinson, A, Deng, X, Liu, C, Horner, M-J, 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, 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, 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, Beane 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, X-O, 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, M-C, Bracci, PM, Canzian, F, Chang, K, Cotterchio, M, Giovannucci, EL, Goggins, M, Hoffman Bolton, JA, Jenab, M, Khaw, K-T, 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, Patiño García, A, Sierrasesúmaga, L, Barkauskas, DA, Gorlick, RG, Purdue, M, Chow, W-H, 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, Caporaso, NE, Tucker, M, Rothman, N, Pérez-Jurado, LA & Chanock, SJ 2012, 'Detectable clonal mosaicism and its relationship to aging and cancer', Nature Genetics, bind 44, nr. 6, s. 651-8. https://doi.org/10.1038/ng.2270

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title = "Detectable clonal mosaicism and its relationship to aging and cancer",

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.",

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year = "2012",

month = may,

day = "6",

doi = "10.1038/ng.2270",

language = "English",

volume = "44",

pages = "651--8",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "6",

}

TY - JOUR

T1 - Detectable clonal mosaicism and its relationship to aging and cancer

AU - Jacobs, Kevin B

AU - Yeager, Meredith

AU - Zhou, Weiyin

AU - Wacholder, Sholom

AU - Wang, Zhaoming

AU - Rodriguez-Santiago, Benjamin

AU - Hutchinson, Amy

AU - Deng, Xiang

AU - Liu, Chenwei

AU - Horner, Marie-Josephe

AU - Cullen, Michael

AU - Epstein, Caroline G

AU - Burdett, Laurie

AU - Dean, Michael C

AU - Chatterjee, Nilanjan

AU - Sampson, Joshua

AU - Chung, Charles C

AU - Kovaks, Joseph

AU - Gapstur, Susan M

AU - Stevens, Victoria L

AU - Teras, Lauren T

AU - Gaudet, Mia M

AU - Albanes, Demetrius

AU - Weinstein, Stephanie J

AU - Virtamo, Jarmo

AU - Taylor, Philip R

AU - Freedman, Neal D

AU - Abnet, Christian C

AU - Goldstein, Alisa M

AU - Hu, Nan

AU - Yu, Kai

AU - Yuan, Jian-Min

AU - Liao, Linda

AU - Ding, Ti

AU - Qiao, You-Lin

AU - Gao, Yu-Tang

AU - Koh, Woon-Puay

AU - Xiang, Yong-Bing

AU - Tang, Ze-Zhong

AU - Fan, Jin-Hu

AU - Aldrich, Melinda C

AU - Amos, Christopher

AU - Blot, William J

AU - Bock, Cathryn H

AU - Gillanders, Elizabeth M

AU - Harris, Curtis C

AU - Haiman, Christopher A

AU - Henderson, Brian E

AU - Kolonel, Laurence N

AU - Le Marchand, Loic

AU - McNeill, Lorna H

AU - Rybicki, Benjamin A

AU - Schwartz, Ann G

AU - Signorello, Lisa B

AU - Spitz, Margaret R

AU - Wiencke, John K

AU - Wrensch, Margaret

AU - Wu, Xifeng

AU - Zanetti, Krista A

AU - Ziegler, Regina G

AU - Figueroa, Jonine D

AU - Garcia-Closas, Montserrat

AU - Malats, Nuria

AU - Marenne, Gaelle

AU - Prokunina-Olsson, Ludmila

AU - Baris, Dalsu

AU - Schwenn, Molly

AU - Johnson, Alison

AU - Landi, Maria Teresa

AU - Goldin, Lynn

AU - Consonni, Dario

AU - Bertazzi, Pier Alberto

AU - Rotunno, Melissa

AU - Rajaraman, Preetha

AU - Andersson, Ulrika

AU - Beane Freeman, Laura E

AU - Berg, Christine D

AU - Buring, Julie E

AU - Butler, Mary A

AU - Carreon, Tania

AU - Feychting, Maria

AU - Ahlbom, Anders

AU - Gaziano, J Michael

AU - Giles, Graham G

AU - Hallmans, Goran

AU - Hankinson, Susan E

AU - Hartge, Patricia

AU - Henriksson, Roger

AU - Inskip, Peter D

AU - Johansen, Christoffer

AU - Landgren, Annelie

AU - McKean-Cowdin, Roberta

AU - Michaud, Dominique S

AU - Melin, Beatrice S

AU - Peters, Ulrike

AU - Ruder, Avima M

AU - Sesso, Howard D

AU - Severi, Gianluca

AU - Shu, Xiao-Ou

AU - Visvanathan, Kala

AU - White, Emily

AU - Wolk, Alicja

AU - Zeleniuch-Jacquotte, Anne

AU - Zheng, Wei

AU - Silverman, Debra T

AU - Kogevinas, Manolis

AU - Gonzalez, Juan R

AU - Villa, Olaya

AU - Li, Donghui

AU - Duell, Eric J

AU - Risch, Harvey A

AU - Olson, Sara H

AU - Kooperberg, Charles

AU - Wolpin, Brian M

AU - Jiao, Li

AU - Hassan, Manal

AU - Wheeler, William

AU - Arslan, Alan A

AU - Bueno-de-Mesquita, H Bas

AU - Fuchs, Charles S

AU - Gallinger, Steven

AU - Gross, Myron D

AU - Holly, Elizabeth A

AU - Klein, Alison P

AU - LaCroix, Andrea

AU - Mandelson, Margaret T

AU - Petersen, Gloria

AU - Boutron-Ruault, Marie-Christine

AU - Bracci, Paige M

AU - Canzian, Federico

AU - Chang, Kenneth

AU - Cotterchio, Michelle

AU - Giovannucci, Edward L

AU - Goggins, Michael

AU - Hoffman Bolton, Judith A

AU - Jenab, Mazda

AU - Khaw, Kay-Tee

AU - Krogh, Vittorio

AU - Kurtz, Robert C

AU - McWilliams, Robert R

AU - Mendelsohn, Julie B

AU - Rabe, Kari G

AU - Riboli, Elio

AU - Tjønneland, Anne

AU - Tobias, Geoffrey S

AU - Trichopoulos, Dimitrios

AU - Elena, Joanne W

AU - Yu, Herbert

AU - Amundadottir, Laufey

AU - Stolzenberg-Solomon, Rachael Z

AU - Kraft, Peter

AU - Schumacher, Fredrick

AU - Stram, Daniel

AU - Savage, Sharon A

AU - Mirabello, Lisa

AU - Andrulis, Irene L

AU - Wunder, Jay S

AU - Patiño García, Ana

AU - Sierrasesúmaga, Luis

AU - Barkauskas, Donald A

AU - Gorlick, Richard G

AU - Purdue, Mark

AU - Chow, Wong-Ho

AU - Moore, Lee E

AU - Schwartz, Kendra L

AU - Davis, Faith G

AU - Hsing, Ann W

AU - Berndt, Sonja I

AU - Black, Amanda

AU - Wentzensen, Nicolas

AU - Brinton, Louise A

AU - Lissowska, Jolanta

AU - Peplonska, Beata

AU - McGlynn, Katherine A

AU - Cook, Michael B

AU - Graubard, Barry I

AU - Kratz, Christian P

AU - Greene, Mark H

AU - Erickson, Ralph L

AU - Hunter, David J

AU - Thomas, Gilles

AU - Hoover, Robert N

AU - Real, Francisco X

AU - Fraumeni, Joseph F

AU - Caporaso, Neil E

AU - Tucker, Margaret

AU - Rothman, Nathaniel

AU - Pérez-Jurado, Luis A

AU - Chanock, Stephen J

PY - 2012/5/6

Y1 - 2012/5/6

N2 - 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.

AB - 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.

KW - Aged

KW - Aging/genetics

KW - Chromosome Aberrations

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Mosaicism

KW - Neoplasms/genetics

KW - Risk

U2 - 10.1038/ng.2270

DO - 10.1038/ng.2270

M3 - Journal article

C2 - 22561519

SN - 1061-4036

VL - 44

SP - 651

EP - 658

JO - Nature Genetics

JF - Nature Genetics

IS - 6

ER -

Detectable clonal mosaicism and its relationship to aging and cancer

Abstract

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