Common Variants at 2q37.3, 8q24.21, 15q21.3 and 16q24.1 Influence Chronic Lymphocytic Leukemia Risk

Overview

Journal Nat Genet

Specialty Genetics

Date 2010 Jan 12

PMID 20062064

Citations 125

Authors

Dalemari Crowther-Swanepoel

Peter Broderick

Maria Chiara Di Bernardo

Sara E Dobbins

Maria Torres

Mahmoud Mansouri

Clara Ruiz-Ponte

Anna Enjuanes

Richard Rosenquist

Angel Carracedo

Jesper Jurlander

Elias Campo

Gunnar Juliusson

Emilio Montserrat

Karin E Smedby

Martin J S Dyer

Estella Matutes

Claire Dearden

Nicola J Sunter

Andrew G Hall

Tryfonia Mainou-Fowler

Graham H Jackson

Geoffrey Summerfield

Robert J Harris

Andrew R Pettitt

David J Allsup

James R Bailey

Guy Pratt

Chris Pepper

Chris Fegan

Anton Parker

David Oscier

James M Allan

Daniel Catovsky

Richard S Houlston

Affiliations

Soon will be listed here.

Abstract

To identify new risk variants for chronic lymphocytic leukemia (CLL), we conducted a genome-wide association study of 299,983 tagging SNPs, with validation in four additional series totaling 2,503 cases and 5,789 controls. We identified four new risk loci for CLL at 2q37.3 (rs757978, FARP2; odds ratio (OR) = 1.39; P = 2.11 x 10(-9)), 8q24.21 (rs2456449; OR = 1.26; P = 7.84 x 10(-10)), 15q21.3 (rs7169431; OR = 1.36; P = 4.74 x 10(-7)) and 16q24.1 (rs305061; OR = 1.22; P = 3.60 x 10(-7)). We also found evidence for risk loci at 15q25.2 (rs783540, CPEB1; OR = 1.18; P = 3.67 x 10(-6)) and 18q21.1 (rs1036935; OR = 1.22; P = 2.28 x 10(-6)). These data provide further evidence for genetic susceptibility to this B-cell hematological malignancy.

Citing Articles

CAT rs1001179 Single Nucleotide Polymorphism Identifies an Aggressive Clinical Behavior in Chronic Lymphocytic Leukemia.

Galasso M, Salaorni V, Moia R, Mozzo V, Lovato E, Cosentino C Hematol Oncol. 2024; 42(6):e70002.

PMID: 39540258 PMC: 11590045. DOI: 10.1002/hon.70002.

The molecular map of CLL and Richter's syndrome.

Sud A, Parry E, Wu C Semin Hematol. 2024; 61(2):73-82.

PMID: 38368146 PMC: 11653080. DOI: 10.1053/j.seminhematol.2024.01.009.

Small molecule inhibition of RNA binding proteins in haematologic cancer.

Jaiswal A, Thaxton M, Scherer G, Sorrentino J, Garg N, Rao D RNA Biol. 2024; 21(1):1-14.

PMID: 38329136 PMC: 10857685. DOI: 10.1080/15476286.2024.2303558.

Autonomous B-cell receptor signaling and genetic aberrations in chronic lymphocytic leukemia-phenotype monoclonal B lymphocytosis in siblings of patients with chronic lymphocytic leukemia.

Quinten E, Sepulveda-Yanez J, Koning M, Eken J, Pfeifer D, Nteleah V Haematologica. 2023; 109(3):824-834.

PMID: 37439337 PMC: 10905078. DOI: 10.3324/haematol.2022.282542.

Multi-omics analysis identifies RFX7 targets involved in tumor suppression and neuronal processes.

Schwab K, Coronel L, Riege K, Sacramento E, Rahnis N, Hackes D Cell Death Discov. 2023; 9(1):80.

PMID: 36864036 PMC: 9981735. DOI: 10.1038/s41420-023-01378-1.

References

Higgins J, Thompson S . Quantifying heterogeneity in a meta-analysis. Stat Med. 2002; 21(11):1539-58. DOI: 10.1002/sim.1186. View

Ikeda M, Longnecker R . The c-Cbl proto-oncoprotein downregulates EBV LMP2A signaling. Virology. 2008; 385(1):183-91. PMC: 2768052. DOI: 10.1016/j.virol.2008.11.018. View

Goldin L, Pfeiffer R, Li X, Hemminki K . Familial risk of lymphoproliferative tumors in families of patients with chronic lymphocytic leukemia: results from the Swedish Family-Cancer Database. Blood. 2004; 104(6):1850-4. DOI: 10.1182/blood-2004-01-0341. View

Hallek M, Cheson B, Catovsky D, Caligaris-Cappio F, Dighiero G, Dohner H . Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008; 111(12):5446-56. PMC: 2972576. DOI: 10.1182/blood-2007-06-093906. View

De Jager P, Jia X, Wang J, de Bakker P, Ottoboni L, Aggarwal N . Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. Nat Genet. 2009; 41(7):776-82. PMC: 2757648. DOI: 10.1038/ng.401. View

Kiemeney L, Thorlacius S, Sulem P, Geller F, Aben K, Stacey S . Sequence variant on 8q24 confers susceptibility to urinary bladder cancer. Nat Genet. 2008; 40(11):1307-12. PMC: 4539560. DOI: 10.1038/ng.229. View

Tuupanen S, Turunen M, Lehtonen R, Hallikas O, Vanharanta S, Kivioja T . The common colorectal cancer predisposition SNP rs6983267 at chromosome 8q24 confers potential to enhanced Wnt signaling. Nat Genet. 2009; 41(8):885-90. DOI: 10.1038/ng.406. View

Catovsky D, Richards S, Matutes E, Oscier D, Dyer M, Bezares R . Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial. Lancet. 2007; 370(9583):230-239. DOI: 10.1016/S0140-6736(07)61125-8. View

Sellick G, Goldin L, Wild R, Slager S, Ressenti L, Strom S . A high-density SNP genome-wide linkage search of 206 families identifies susceptibility loci for chronic lymphocytic leukemia. Blood. 2007; 110(9):3326-33. PMC: 2200912. DOI: 10.1182/blood-2007-05-091561. View

10.

Weiss N . Geographical variation in the incidence of the leukemias and lymphomas. Natl Cancer Inst Monogr. 1979; (53):139-42. View

11.

Hamblin T, Davis Z, Gardiner A, Oscier D, Stevenson F . Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood. 1999; 94(6):1848-54. View

12.

Sellick G, Wade R, Richards S, Oscier D, Catovsky D, Houlston R . Scan of 977 nonsynonymous SNPs in CLL4 trial patients for the identification of genetic variants influencing prognosis. Blood. 2007; 111(3):1625-33. DOI: 10.1182/blood-2007-08-110130. View

13.

Goldin L, Ishibe N, Sgambati M, Marti G, Fontaine L, Lee M . A genome scan of 18 families with chronic lymphocytic leukaemia. Br J Haematol. 2003; 121(6):866-73. DOI: 10.1046/j.1365-2141.2003.04372.x. View

14.

Zhang X, Supakar P, Wu K, Ehrlich K, Ehrlich M . An MDBP site in the first intron of the human c-myc gene. Cancer Res. 1990; 50(21):6865-9. View

15.

Wang H, Morse 3rd H . IRF8 regulates myeloid and B lymphoid lineage diversification. Immunol Res. 2008; 43(1-3):109-17. PMC: 2803682. DOI: 10.1007/s12026-008-8055-8. View

16.

Sellick G, Webb E, Allinson R, Matutes E, Dyer M, Jonsson V . A high-density SNP genomewide linkage scan for chronic lymphocytic leukemia-susceptibility loci. Am J Hum Genet. 2005; 77(3):420-9. PMC: 1226207. DOI: 10.1086/444472. View

17.

Damle R, Wasil T, Fais F, Ghiotto F, Valetto A, Allen S . Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood. 1999; 94(6):1840-7. View

18.

van Krieken J, Langerak A, Macintyre E, Kneba M, Hodges E, Garcia Sanz R . Improved reliability of lymphoma diagnostics via PCR-based clonality testing: report of the BIOMED-2 Concerted Action BHM4-CT98-3936. Leukemia. 2006; 21(2):201-6. DOI: 10.1038/sj.leu.2404467. View

19.

Tomlinson I, Webb E, Carvajal-Carmona L, Broderick P, Kemp Z, Spain S . A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21. Nat Genet. 2007; 39(8):984-8. DOI: 10.1038/ng2085. View

20.

Grubor V, Krasnitz A, Troge J, Meth J, Lakshmi B, Kendall J . Novel genomic alterations and clonal evolution in chronic lymphocytic leukemia revealed by representational oligonucleotide microarray analysis (ROMA). Blood. 2008; 113(6):1294-303. DOI: 10.1182/blood-2008-05-158865. View