Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia

被引：156

作者：

Berndt, Sonja I. ^{[1
]}

Skibola, Christine F. ^{[2
,3
]}

Joseph, Vijai ^{[4
]}

Camp, Nicola J. ^{[5
]}

Nieters, Alexandra ^{[6
]}

Wang, Zhaoming ^{[7
]}

Cozen, Wendy ^{[8
]}

Monnereau, Alain ^{[9
,10
]}

Wang, Sophia S. ^{[11
]}

Kelly, Rachel S. ^{[12
]}

Lan, Qing ^{[1
]}

Teras, Lauren R. ^{[13
]}

Chatterjee, Nilanjan ^{[1
]}

Chung, Charles C. ^{[1
,7
]}

Yeager, Meredith ^{[7
]}

Brooks-Wilson, Angela R. ^{[14
,15
]}

Hartge, Patricia ^{[1
]}

Purdue, Mark P. ^{[1
]}

Birmann, Brenda M. ^{[16
,17
]}

Armstrong, Bruce K. ^{[18
]}

Cocco, Pierluigi ^{[19
]}

Zhang, Yawei ^{[20
]}

Severi, Gianluca ^{[21
]}

Zeleniuch-Jacquotte, Anne ^{[22
]}

Lawrence, Charles ^{[23
]}

Burdette, Laurie ^{[7
]}

Yuenger, Jeffrey ^{[7
]}

Hutchinson, Amy ^{[7
]}

Jacobs, Kevin B. ^{[7
]}

Call, Timothy G. ^{[24
]}

Shanafelt, Tait D. ^{[25
]}

Novak, Anne J. ^{[25
]}

Kay, Neil E. ^{[24
]}

Liebow, Mark ^{[26
]}

Wang, Alice H. ^{[27
]}

Smedby, Karin E. ^{[28
,29
]}

Adami, Hans-Olov ^{[30
,31
]}

Melbye, Mads ^{[32
]}

Glimelius, Bengt ^{[29
,33
]}

Chang, Ellen T. ^{[34
,35
]}

Glenn, Martha ^{[36
]}

Curtin, Karen ^{[5
]}

Cannon-Albright, Lisa A. ^{[5
,37
]}

Jones, Brandt ^{[5
]}

Diver, W. Ryan ^{[13
]}

Link, Brian K. ^{[38
]}

Weiner, George J. ^{[38
]}

Conde, Lucia ^{[2
,3
]}

Bracci, Paige M. ^{[39
]}

Riby, Jacques ^{[2
]}

机构：

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

[2] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA

[3] Univ Alabama Birmingham, Sch Publ Hlth, Birmingham, AL 35294 USA

[4] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA

[5] Univ Utah, Sch Med, Dept Internal Med, Salt Lake City, UT USA

[6] Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, Freiburg, Hesse, Germany

[7] NCI, Canc Genom Res Lab, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[8] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

[9] INSERM, U1018 EQ6, Villejuif, France

[10] Inst Bergonie, Registre Hemopathies Malignes Gironde, Bordeaux, France

[11] City Hope Beckman Res Inst, Div Canc Etiol, Duarte, CA USA

[12] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC HPA Ctr Environm & Hlth, London, England

[13] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA

[14] BC Canc Agcy, Genome Sci Ctr, Vancouver, BC, Canada

[15] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada

[16] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA

[17] Harvard Univ, Sch Med, Boston, MA USA

[18] Univ Sydney, Sydney Sch Publ Hlth, Sydney, NSW 2006, Australia

[19] Univ Cagliari, Dept Publ Hlth Clin & Mol Med, Cagliari, Italy

[20] Yale Univ, Sch Publ Hlth, Dept Environm Hlth Sci, New Haven, CT USA

[21] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic, Australia

[22] NYU, Sch Med, Dept Populat Hlth, New York, NY USA

[23] WESTAT Corp, Hlth Studies Sector, Rockville, MD 20850 USA

[24] Mayo Clin, Coll Med, Div Hematol, Rochester, MN USA

[25] Mayo Clin, Coll Med, Dept Med, Rochester, MN USA

[26] Mayo Clin, Coll Med, Div Gen Internal Med, Rochester, MN USA

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

[28] Karolinska Inst, Dept Med Solna, Stockholm, Sweden

[29] Karolinska Inst, Karolinska Univ Hosp Solna, Dept Pathol & Oncol, Stockholm, Sweden

[30] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[31] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[32] Statens Serum Inst, Div Hlth Surveillance & Res, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark

[33] Uppsala Univ, Dept Radiol Oncol & Radiat Sci, Uppsala, Sweden

[34] Exponent Inc, Hlth Sci, Ctr Epidemiol & Computat Biol, Menlo Pk, CA USA

[35] Stanford Univ, Sch Med, Div Epidemiol, Dept Hlth Res & Policy, Stanford, CA 94305 USA

[36] Huntsman Canc Inst, Dept Internal Med, Salt Lake City, UT USA

[37] George E Wahlen Dept Vet Affairs Med Ctr, Salt Lake City, UT USA

[38] Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA

[39] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA

[40] Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA

[41] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA

[42] Inst Invest Biomed Bellvitge IDIBELL, Canc Epidemiol Res Programme, Unit Infect & Canc UNIC, Barcelona, Spain

[43] CIBERESP, Barcelona, Spain

[44] German Canc Res Ctr, Div Canc Epidemiol, Baden, Switzerland

[45] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA

[46] Int Agcy Res Canc, Genet Sect, Grp Genet Epidemiol, F-69372 Lyon, France

[47] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic

[48] Univ Burgundy, Registre Hemopathies Malignes Cote dOr, EA 4184, Dijon, France

[49] Int Agcy Res Canc, Genet Sect, Genet Canc Susceptibil Grp, F-69372 Lyon, France

[50] Dublin City Univ, Sch Nursing & Human Sci, Dublin 9, Leinster, Ireland

来源：

NATURE GENETICS | 2013年 / 45卷 / 08期

基金：

美国国家卫生研究院;

关键词：

CANCER SUSCEPTIBILITY LOCI; FAS GENE-MUTATIONS; LINKAGE DISEQUILIBRIUM; EPIDEMIOLOGIC RESEARCH; TERT-CLPTM1L LOCUS; LYMPHOID NEOPLASMS; COMMON VARIATION; BREAST-CANCER; VARIANTS; APOPTOSIS;

D O I：

10.1038/ng.2652

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 x 10(-14)), 18q21.33 (BCL2, P = 7.76 x 10(-11)), 11p15.5 (C11orf21, P = 2.15 x 10(-10)), 4q25 (LEF1, P = 4.24 x 10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 x 10(-9)), 9p21.3 (CDKN2B-AS1, P = 1.27 x 10(-8)), 18q21.32 (PMAIP1, P = 2.51 x 10(-8)), 15q15.1 (BMF, P = 2.71 x 10(-10)) and 2p22.2 (QPCT, P = 1.68 x 10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 x 10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 x 10(-8)) and 5p15.33 (TERT, P = 1.92 x 10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.

引用

页码：868 / 876

页数：9

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