Genome-wide association study identifies a novel susceptibility locus at 6p21.3 among familial CLL

被引：99

作者：

Slager, Susan L. ^{[1
]}

Rabe, Kari G. ^{[1
]}

Achenbach, Sara J. ^{[1
]}

Vachon, Celine M. ^{[1
]}

Goldin, Lynn R. ^{[2
]}

Strom, Sara S. ^{[3
]}

Lanasa, Mark C. ^{[4
]}

Spector, Logan G. ^{[5
]}

Rassenti, Laura Z. ^{[6
]}

Leis, Jose F. ^{[1
]}

Camp, Nicola J. ^{[7
]}

Glenn, Martha ^{[7
]}

Kay, Neil E. ^{[1
]}

Cunningham, Julie M. ^{[1
]}

Hanson, Curtis A. ^{[1
]}

Marti, Gerald E. ^{[8
]}

Weinberg, J. Brice ^{[4
,9
]}

Morrison, Vicki A. ^{[5
,10
]}

Link, Brian K. ^{[11
]}

Call, Timothy G. ^{[1
]}

Caporaso, Neil E. ^{[2
]}

Cerhan, James R. ^{[1
]}

机构：

[1] Mayo Clin, Coll Med, Rochester, MN 55905 USA

[2] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[3] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[4] Duke Univ, Med Ctr, Durham, NC USA

[5] Univ Minnesota, Minneapolis, MN USA

[6] Univ Calif San Diego, Med Ctr, Moores Canc Ctr, La Jolla, CA 92093 USA

[7] Univ Utah, Sch Med, Salt Lake City, UT USA

[8] US FDA, Bethesda, MD 20014 USA

[9] Durham Vet Adm Med Ctr, Durham, NC USA

[10] Minneapolis Vet Adm Med Ctr, Minneapolis, MN USA

[11] Univ Iowa, Iowa City, IA USA

来源：

BLOOD | 2011年 / 117卷 / 06期

基金：

美国国家卫生研究院;

关键词：

CHRONIC LYMPHOCYTIC-LEUKEMIA; RISK; VARIANTS; LYMPHOMAS; GENES;

D O I：

10.1182/blood-2010-09-308205

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Prior genome-wide association (GWA) studies have identified 10 susceptibility loci for risk of chronic lymphocytic leukemia (CLL). To identify additional loci, we performed a GWA study in 407 CLL cases (of which 102 had a family history of CLL) and 296 controls. Moreover, given the strong familial risk of CLL, we further subset our GWA analysis to the CLL cases with a family history of CLL to identify loci specific to these familial CLL cases. Our top hits from these analyses were evaluated in an additional sample of 252 familial CLL cases and 965 controls. Using all available data, we identified and confirmed an independent association of 4 single-nucleotide polymorphisms (SNPs) that met genome-wide statistical significance within the IRF8 (interferon regulatory factor 8) gene (combined P values <= 3.37 x 10(-8)), located in the previously identified 16q24.1 locus. Subsetting to familial CLL cases, we identified and confirmed a new locus on chromosome 6p21.3 (combined P value = 6.92 x 10(-9)). This novel region harbors the HLA-DQA1 and HLA-DRB5 genes. Finally, we evaluated the 10 previously reported SNPs in the overall sample and replicated 8 of them. Our findings support the hypothesis that familial CLL cases have additional genetic variants not seen in sporadic CLL. Additional loci among familial CLL cases may be identified through larger studies. (Blood. 2011;117(6):1911-1916)

引用

页码：1911 / 1916

页数：6

共 17 条

[1] Haploview: analysis and visualization of LD and haplotype maps [J].

Barrett, JC ;

Fry, B ;

Maller, J ;

Daly, MJ .

BIOINFORMATICS, 2005, 21 (02) :263-265

[2] Genetic variation in 1253 immune and inflammation genes and risk of non-Hodgkin lymphoma [J].

Cerhan, James R. ;

Ansell, Stephen M. ;

Fredericksen, Zachary S. ;

Kay, Neil E. ;

Liebow, Mark ;

Call, Timothy G. ;

Dogan, Ahmet ;

Cunningham, Julie M. ;

Wang, Alice H. ;

Liu-Mares, Wen ;

Macon, William R. ;

Jelinek, Diane ;

Witzig, Thomas E. ;

Habermann, Thomas M. ;

Slager, Susan L. .

BLOOD, 2007, 110 (13) :4455-4463

[3] Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32 [J].

Conde, Lucia ;

Halperin, Eran ;

Akers, Nicholas K. ;

Brown, Kevin M. ;

Smedby, Karin E. ;

Rothman, Nathaniel ;

Nieters, Alexandra ;

Slager, Susan L. ;

Brooks-Wilson, Angela ;

Agana, Luz ;

Riby, Jacques ;

Liu, Jianjun ;

Adami, Hans-Olov ;

Darabi, Hatef ;

Hjalgrim, Henrik ;

Low, Hui-Qi ;

Humphreys, Keith ;

Melbye, Mads ;

Chang, Ellen T. ;

Glimelius, Bengt ;

Cozen, Wendy ;

Davis, Scott ;

Hartge, Patricia ;

Morton, Lindsay M. ;

Schenk, Maryjean ;

Wang, Sophia S. ;

Armstrong, Bruce ;

Kricker, Anne ;

Milliken, Sam ;

Purdue, Mark P. ;

Vajdic, Claire M. ;

Boyle, Peter ;

Lan, Qing ;

Zahm, Shelia H. ;

Zhang, Yawei ;

Zheng, Tongzhang ;

Becker, Nikolaus ;

Benavente, Yolanda ;

Boffetta, Paolo ;

Brennan, Paul ;

Butterbach, Katja ;

Cocco, Pierluigi ;

Foretova, Lenka ;

Maynadie, Marc ;

de Sanjose, Silvia ;

Staines, Anthony ;

Spinelli, John J. ;

Achenbach, Sara J. ;

Call, Timothy G. ;

Camp, Nicola J. .

NATURE GENETICS, 2010, 42 (08) :661-664

[4] Common variants at 2q37.3, 8q24.21, 15q21.3 and 16q24.1 influence chronic lymphocytic leukemia risk [J].

Crowther-Swanepoel, Dalemari ;

Broderick, Peter ;

Di Bernardo, Maria Chiara ;

Dobbins, Sara E. ;

Torres, Maria ;

Mansouri, Mahmoud ;

Ruiz-Ponte, Clara ;

Enjuanes, Anna ;

Rosenquist, Richard ;

Carracedo, Angel ;

Jurlander, Jesper ;

Campo, Elias ;

Juliusson, Gunnar ;

Montserrat, Emilio ;

Smedby, Karin E. ;

Dyer, Martin J. S. ;

Matutes, Estella ;

Dearden, Claire ;

Sunter, Nicola J. ;

Hall, Andrew G. ;

Mainou-Fowler, Tryfonia ;

Jackson, Graham H. ;

Summerfield, Geoffrey ;

Harris, Robert J. ;

Pettitt, Andrew R. ;

Allsup, David J. ;

Bailey, James R. ;

Pratt, Guy ;

Pepper, Chris ;

Fegan, Chris ;

Parker, Anton ;

Oscier, David ;

Allan, James M. ;

Catovsky, Daniel ;

Houlston, Richard S. .

NATURE GENETICS, 2010, 42 (02) :132-U59

[5] A genome-wide association study identifies six susceptibility loci for chronic lymphocytic leukemia [J].

Di Bernardo, Maria Chiara ;

Crowther-Swanepoel, Dalemari ;

Broderick, Peter ;

Webb, Emily ;

Sellick, Gabrielle ;

Wild, Ruth ;

Sullivan, Kate ;

Vijayakrishnan, Jayaram ;

Wang, Yufei ;

Pittman, Alan M. ;

Sunter, Nicola J. ;

Hall, Andrew G. ;

Dyer, Martin J. S. ;

Matutes, Estella ;

Dearden, Claire ;

Mainou-Fowler, Tryfonia ;

Jackson, Graham H. ;

Summerfield, Geoffrey ;

Harris, Robert J. ;

Pettitt, Andrew R. ;

Hillmen, Peter ;

Allsup, David J. ;

Bailey, James R. ;

Pratt, Guy ;

Pepper, Chris ;

Fegan, Chris ;

Allan, James M. ;

Catovsky, Daniel ;

Houlston, Richard S. .

NATURE GENETICS, 2008, 40 (10) :1204-1210

[6] Common occurrence of monoclonal B-cell lymphocytosis among members of high-risk CLL families [J].

Goldin, Lynn R. ;

Lanasa, Mark C. ;

Slager, Susan L. ;

Cerhan, James R. ;

Vachon, Celine M. ;

Strom, Sara S. ;

Camp, Nicola J. ;

Spector, Logan G. ;

Leis, Jose F. ;

Morrison, Vicki A. ;

Glenn, Martha ;

Rabe, Kari G. ;

Achenbach, Sara J. ;

Algood, Sallie D. ;

Abbasi, Fatima ;

Fontaine, Laura ;

Yau, Michelle ;

Rassenti, Laura Z. ;

Kay, Neil E. ;

Call, Timothy G. ;

Hanson, Curtis A. ;

Weinberg, J. Brice ;

Marti, Gerald E. ;

Caporaso, Neil E. .

BRITISH JOURNAL OF HAEMATOLOGY, 2010, 151 (02) :152-158

[7] Familial chronic lymphocytic leukemia [J].

Goldin, Lynn R. ;

Slager, Susan L. ;

Caporaso, Neil E. .

CURRENT OPINION IN HEMATOLOGY, 2010, 17 (04) :350-355

[8] Elevated risk of chronic lymphocytic leukemia and other indolent non-Hodgkin's lymphomas among relatives of patients with chronic lymphocytic leukemia [J].

Goldin, Lynn R. ;

Bjorkholm, Magnus ;

Kristinsson, Sigurdur Y. ;

Turesson, Ingemar ;

Landgren, Ola .

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2009, 94 (05) :647-653

[9]

Jaffe E.S., 2001, PATHOLOGY GENETICS T, V3

[10] B-Cell Clones as Early Markers for Chronic Lymphocytic Leukemia [J].

Landgren, Ola ;

Albitar, Maher ;

Ma, Wanlong ;

Abbasi, Fatima ;

Hayes, Richard B. ;

Ghia, Paolo ;

Marti, Gerald E. ;

Caporaso, Neil E. .

NEW ENGLAND JOURNAL OF MEDICINE, 2009, 360 (07) :659-667

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