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Smoking, variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2), and risk of non-Hodgkin lymphoma: a pooled analysis within the InterLymph consortium

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Abstract

Purpose

Studies of smoking and risk of non-Hodgkin lymphoma (NHL) have yielded inconsistent results, possibly due to subtype heterogeneity and/or genetic variation impacting the metabolism of tobacco-derived carcinogens, including substrates of the N-acetyltransferase enzymes NAT1 and NAT2.

Methods

We conducted a pooled analysis of 5,026 NHL cases and 4,630 controls from seven case–control studies in the international lymphoma epidemiology consortium to examine associations between smoking, variation in the N-acetyltransferase genes NAT1 and NAT2, and risk of NHL subtypes. Smoking data were harmonized across studies, and genetic variants in NAT1 and NAT2 were used to infer acetylation phenotype of the NAT1 and NAT2 enzymes, respectively. Pooled odds ratios (ORs) and 95 % confidence intervals (95 % CIs) for risk of NHL and subtypes were calculated using joint fixed effects unconditional logistic regression models.

Results

Current smoking was associated with a significant 30 % increased risk of follicular lymphoma (n = 1,176) but not NHL overall or other NHL subtypes. The association was similar among NAT2 slow (OR 1.36; 95 % CI 1.07–1.75) and intermediate/rapid (OR 1.27; 95 % CI 0.95–1.69) acetylators (p interaction = 0.82) and also did not differ by NAT1*10 allelotype. Neither NAT2 phenotype nor NAT1*10 allelotype was associated with risk of NHL overall or NHL subtypes.

Conclusion

The current findings provide further evidence for a modest association between current smoking and follicular lymphoma risk and suggest that this association may not be influenced by variation in the N-acetyltransferase enzymes.

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Acknowledgments

Intramural Research Program of the National Cancer Institute; Spanish Ministry of Health FISS grant PI11/01810, AGAUR_SGR01465, and CIBERESP 06/06/0073 (EpiLymph-Spain); Swedish Cancer Society (090659); Danish Medical Research Council (FSS 09-63424); National Cancer Institute (CA069269-01 and CA92153-01); National Health and Medical Research Council, Australia, grant 990920.

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Authors and Affiliations

  1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd., EPS 7090, Bethesda, MD, 20892, USA

    Todd M. Gibson, Joshua N. Sampson, Nathaniel Rothman & Lindsay M. Morton

  2. Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA

    Todd M. Gibson

  3. Unit of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institute, Stockholm, Sweden

    Karin E. Smedby

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

    Christine F. Skibola, Lucia Conde, Jacques Riby & Casey Palmers

  5. Department of Pharmacology and Toxicology and James Graham Brown Cancer Center, School of Medicine, University of Louisville, Louisville, KY, USA

    David W. Hein

  6. Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA

    Susan L. Slager & James R. Cerhan

  7. Unit of Infections and Cancer, Cancer Epidemiology Research Programme, Institut Català d’Oncologia, IDIBELL, Barcelona, Spain

    Silvia de Sanjosé & Yolanda Benavente

  8. CIBER Epidemiologia y Salud Pública, Madrid, Spain

    Silvia de Sanjosé

  9. Adult Cancer Program, University of New South Wales, Sydney, NSW, Australia

    Claire M. Vajdic

  10. Lowy Cancer Research Center, Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia

    Claire M. Vajdic

  11. Yale School of Public Health, Yale University, New Haven, CT, USA

    Yawei Zhang, Tongzhang Zheng & Theodore R. Holford

  12. Department of Health Studies, University of Chicago, Chicago, IL, USA

    Brian C.-H. Chiu

  13. Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute and the City of Hope, Duarte, CA, USA

    Sophia S. Wang

  14. Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark

    Henrik Hjalgrim

  15. Centre of Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany

    Alexandra Nieters

  16. Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco, San Francisco, CA, USA

    Paige M. Bracci & Elizabeth A. Holly

  17. School of Public Health, University of Sydney, Sydney, NSW, Australia

    Anne Kricker & Bruce K. Armstrong

  18. The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA

    Carol Kolar

  19. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden

    Hatef Darabi

  20. Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany

    Nikolaus Becker & Katja Butterbach

  21. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA

    Dennis D. Weisenburger

  22. Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA, USA

    Anneclaire J. De Roos

  23. Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Anneclaire J. De Roos

  24. Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Wendy Cozen

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  1. Todd M. Gibson
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  2. Karin E. Smedby
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  33. Lindsay M. Morton
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Correspondence to Todd M. Gibson.

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Gibson, T.M., Smedby, K.E., Skibola, C.F. et al. Smoking, variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2), and risk of non-Hodgkin lymphoma: a pooled analysis within the InterLymph consortium. Cancer Causes Control 24, 125–134 (2013). https://doi.org/10.1007/s10552-012-0098-4

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