Abstract

To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 × 10−29 and rs7755224, combined P = 2.00 × 10−19; r2 = 1.0), supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility. We also found confirmatory evidence of a previously reported association between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined P = 4.24 × 10−9).

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Acknowledgements

This work was supported by grants CA122663 and CA104682 from the National Cancer Institute (NCI), US National Institutes of Health (NIH) (C.F.S.); grants CA45614 and CA89745 from the NCI, NIH (E.A.H.); the American Cancer Society (IRG-07-06401) and a charitable donation by S. Chase (K.B.). E.H. is a faculty fellow of the Edmond J. Safra Bioinformatics program at Tel-Aviv University. SCALE study: We thank X.Y. Chen, H.B. Toh, K.K. Heng and W.Y. Meah from Genome Institute of Singapore for their support in genotyping analyses. We are also grateful to L. Klareskog, Center for Molecular Medicine, and L. Alfredsson, Institute of Environmental Medicine at the Karolinska Institute, Stockholm, Sweden, for sharing DNA from their EIRA study control population and to E. Rehnberg for help with imputing genotypes in the SCALE study. The following agencies contributed funding to SCALE that facilitated the present project: Agency for Science and Technology and Research of Singapore (A*STAR), NCI, the Swedish Cancer Society, the Swedish Research Council and the Danish Medical Research Council. GEC-Mayo Study: This study is supported by grants R01 CA91253 and R01 CA118444 from the NCI. NCI-SEER study: We thank P. Hui of the Information Management Services, Inc. for programming support, and we acknowledge the contributions of the staff and scientists at the SEER centers of Iowa, Los Angeles, Detroit and Seattle for conducting the study's field effort. We especially acknowledge the contributions of study site principal investigator L. Bernstein (Los Angeles). The NCI-SEER study was supported by the Intramural Research Program of the NIH (NCI) and by US Public Health Service (PHS) contracts N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010 and N02-PC-71105. Yale study: This study is supported by grant CA62006 from the NCI and the Intramural Research Program of the NIH (NCI). NSW study: The NSW study was supported by a National Health and Medical Research Council of Australia project grant, Cancer Council NSW, a University of Sydney Medical Foundation Program Grant and the Intramural Research Program of the NIH (NCI). BC study: Funding for the British Columbia study was from the Canadian Cancer Society and the Canadian Institutes of Health Research. A.B.-W. is a Senior Scholar of the Michael Smith Foundation for Health Research. EpiLymph study: Funding was available from the German José Carreras Leukemia Foundation (DJCLS_R04/08 and R07/26f) (A.N.), the EC 5th Framework Program Quality of Life grant No. QLK4-CT-2000-00422 (P. Boffetta, P. Brennan), the Federal Office for Radiation Protection grants No. StSch4261 and StSch4420 (Germany), the Spanish Ministry of Health grants Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP) (06/02/0073), FIS 08-1555 and Marato TV3 (051210) (Spain), La Fondation de France, no. 1999 0084 71 (M. Maynadié), Compagnia di San Paolo di Torino, Programma Oncologia 2001 (P.C.), the Health Research Board, Ireland, and the Ministry of Health of the Czech Republic, MZ0 MOU 2005 (L.F.).

Author information

Affiliations

  1. Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, Berkeley, California, USA.

    • Lucia Conde
    • , Nicholas K Akers
    • , Luz Agana
    • , Jacques Riby
    • , Martyn T Smith
    •  & Christine F Skibola
  2. Molecular Microbiology and Biotechnology Department, Tel-Aviv University, Tel-Aviv, Israel.

    • Eran Halperin
  3. International Computer Science Institute, Berkeley, California, USA.

    • Eran Halperin
  4. Integrative Cancer Genomics Division, Translational Genomics Research Institute (TGen), Phoenix, Arizona, USA.

    • Kevin M Brown
  5. Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden.

    • Karin E Smedby
  6. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

    • Nathaniel Rothman
    • , Patricia Hartge
    • , Lindsay M Morton
    • , Sophia S Wang
    • , Mark P Purdue
    • , Qing Lan
    • , Shelia H Zahm
    • , Neil E Caporaso
    • , Lynn R Goldin
    •  & Stephen Chanock
  7. Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.

    • Alexandra Nieters
    • , Nikolaus Becker
    •  & Katja Butterbach
  8. Molecular Epidemiology, Centre of Chronic Immunodeficiency, University of Freiburg Medical Centre, Freiburg, Germany.

    • Alexandra Nieters
  9. Mayo Clinic College of Medicine, Rochester, Minnesota, USA.

    • Susan L Slager
    • , Sara J Achenbach
    • , Timothy G Call
    • , James R Cerhan
    • , Julie M Cunningham
    • , Curtis A Hanson
    • , Neil E Kay
    • , Jose F Leis
    • , Kari G Rabe
    •  & Celine M Vachon
  10. British Columbia Cancer Research Center, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.

    • Angela Brooks-Wilson
    •  & John J Spinelli
  11. Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Vancouver, British Columbia, Canada.

    • Angela Brooks-Wilson
  12. Human Genetics, Genome Institute of Singapore, A*STAR, Singapore.

    • Jianjun Liu
    •  & Hui-Qi Low
  13. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

    • Hans-Olov Adami
    • , Hatef Darabi
    •  & Keith Humphreys
  14. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.

    • Hans-Olov Adami
  15. Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.

    • Henrik Hjalgrim
    •  & Mads Melbye
  16. Cancer Prevention Institute of California (formerly the Northern California Cancer Center), Fremont, California, USA.

    • Ellen T Chang
  17. Division of Epidemiology, Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California, USA.

    • Ellen T Chang
  18. Department of Oncology and Pathology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.

    • Bengt Glimelius
  19. Department of Oncology, Radiology and Clinical Immunology, Akademiska Hospital, Uppsala University, Uppsala, Sweden.

    • Bengt Glimelius
  20. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

    • Wendy Cozen
  21. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

    • Scott Davis
  22. Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, Michigan, USA.

    • Maryjean Schenk
  23. Division of Etiology, Beckman Research Institute and the City of Hope, Duarte, California, USA.

    • Sophia S Wang
  24. Sydney School of Public Health, The University of Sydney, Sydney, Australia.

    • Bruce Armstrong
    •  & Anne Kricker
  25. Department of Haematology, St. Vincent's Hospital, Sydney, Australia.

    • Sam Milliken
  26. University of New South Wales Cancer Research Center, Prince of Wales Clinical School, Sydney, Australia.

    • Claire M Vajdic
  27. International Prevention Research Institute, Lyon, France.

    • Peter Boyle
    •  & Paolo Boffetta
  28. School of Public Health, Yale University, New Haven, Connecticut, USA.

    • Yawei Zhang
    •  & Tongzhang Zheng
  29. Unit of Infections and Cancer (UNIC), Cancer Epidemiology Research Programme, Catalan Institute of Oncology, Barcelona, Spain.

    • Yolanda Benavente
    •  & Silvia de Sanjosé
  30. The Tisch Cancer Institute, Mount Sinai School of Medicine, New York, New York, USA.

    • Paolo Boffetta
  31. International Agency for Research on Cancer, Lyon, France.

    • Paul Brennan
  32. Department of Public Health, Occupational Health Section, University of Cagliari, Cagliari, Italy.

    • Pierluigi Cocco
  33. Masaryk Memorial Cancer Institute, Brno, Czech Republic.

    • Lenka Foretova
  34. Registry of Hematological Malignancies, EA4184, University of Burgundy, University Hospital of Dijon, Dijon, France.

    • Marc Maynadié
  35. School of Public Health and Population Science, University College Dublin, Dublin, Ireland.

    • Anthony Staines
  36. School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.

    • John J Spinelli
  37. University of Utah School of Medicine, Department of Biomedical Informatics, Salt Lake City, Utah, USA.

    • Nicola J Camp
    •  & Martha Glenn
  38. Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.

    • Mark C Lanasa
    •  & J Brice Weinberg
  39. Division of Cell and Gene Therapies, Office of Cellular, Tissues and Gene Therapies, US Food and Drug Administration, US National Institutes of Health, Bethesda, Maryland, USA.

    • Gerald E Marti
  40. Moores Cancer Center, University of California, San Diego, La Jolla, California, USA.

    • Laura Z Rassenti
  41. Prevention and Etiology Research Program, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.

    • Logan G Spector
  42. Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.

    • Sara S Strom
  43. Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.

    • Elizabeth A Holly
    •  & Paige M Bracci

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Contributions

Design and interpretation of overall study: C.F.S., E.H., K.M.B., M.T.S., P.M.B. Primary data analysis: L.C., E.H. Drafting of manuscript: L.C., C.F.S. Critical revision of manuscript: E.H., K.M.B., A.B.-W., B.A., C.M. Vajdic., S.C., M.T.S., P.M.B. Study design, genotyping and statistical analysis of individual studies: SF1, SF1B and SF2: L.C., E.H., J.R., N.K.A., L.A., E.A.H., M.T.S., P.M.B., C.F.S. SCALE: K.E.S., J.L., H.-O.A., H.D., H.H., H.-Q.L., K.H., M. Melbye, E.T.C., B.G. NCI-SEER: N.R., W.C., S.D., P.H., L.M.M., M.S., S.S.W., S.C., J.R.C. NSW: B.A., A.K., S.M., M.P.P., C.M. Vajdic. Yale: P. Boyle, Q.L., S.H.Z., Y.Z., T.Z. EpiLymph: A.N., N.B., Y.B., P. Boffetta, P. Brennan, K.B., P.C., L.F., M. Maynadié, S.de.S., A.S. BC: A.B.-W., J.J.S. Mayo-GEC: S.L.S., S.J.A., T.G.C., M.G., N.J.C., N.E.C., J.R.C., J.M.C., L.R.G., C.A.H., N.E.K., M.C.L., J.F.L., G.E.M., K.G.R., L.Z.R., L.G.S., S.S.S., C.M. Vachon, J.B.W. All authors contributed to the final manuscript and approved its content.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Christine F Skibola.

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DOI

https://doi.org/10.1038/ng.626

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