Original Paper

Cancer Causes & Control

, Volume 24, Issue 1, pp 125-134

First online:

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

  • Todd M. GibsonAffiliated withDivision of Cancer Epidemiology and Genetics, National Cancer InstituteCancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute Email author 
  • , Karin E. SmedbyAffiliated withUnit of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institute
  • , Christine F. SkibolaAffiliated withDivision of Environmental Health Sciences, School of Public Health, University of California, Berkeley
  • , David W. HeinAffiliated withDepartment of Pharmacology and Toxicology and James Graham Brown Cancer Center, School of Medicine, University of Louisville
  • , Susan L. SlagerAffiliated withDepartment of Health Sciences Research, Mayo Clinic College of Medicine
  • , Silvia de SanjoséAffiliated withUnit of Infections and Cancer, Cancer Epidemiology Research Programme, Institut Català d’Oncologia, IDIBELLCIBER Epidemiologia y Salud Pública
  • , Claire M. VajdicAffiliated withAdult Cancer Program, University of New South WalesLowy Cancer Research Center, Prince of Wales Clinical School, University of New South Wales
  • , Yawei ZhangAffiliated withYale School of Public Health, Yale University
  • , Brian C.-H. ChiuAffiliated withDepartment of Health Studies, University of Chicago
    • , Sophia S. WangAffiliated withDivision of Cancer Etiology, Department of Population Sciences, Beckman Research Institute and the City of Hope
    • , Henrik HjalgrimAffiliated withDepartment of Epidemiology Research, Statens Serum Institut
    • , Alexandra NietersAffiliated withCentre of Chronic Immunodeficiency, University Medical Center Freiburg
    • , Paige M. BracciAffiliated withDepartment of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco
    • , Anne KrickerAffiliated withSchool of Public Health, University of Sydney
    • , Tongzhang ZhengAffiliated withYale School of Public Health, Yale University
    • , Carol KolarAffiliated withThe Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center
    • , James R. CerhanAffiliated withDepartment of Health Sciences Research, Mayo Clinic College of Medicine
    • , Hatef DarabiAffiliated withDepartment of Medical Epidemiology and Biostatistics, Karolinska Institute
    • , Nikolaus BeckerAffiliated withDivision of Cancer Epidemiology, German Cancer Research Center
    • , Lucia CondeAffiliated withDivision of Environmental Health Sciences, School of Public Health, University of California, Berkeley
    • , Theodore R. HolfordAffiliated withYale School of Public Health, Yale University
    • , Dennis D. WeisenburgerAffiliated withDepartment of Pathology and Microbiology, University of Nebraska Medical Center
    • , Anneclaire J. De RoosAffiliated withDepartment of Epidemiology, School of Public Health and Community Medicine, University of WashingtonProgram in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center
    • , Katja ButterbachAffiliated withDivision of Cancer Epidemiology, German Cancer Research Center
    • , Jacques RibyAffiliated withDivision of Environmental Health Sciences, School of Public Health, University of California, Berkeley
    • , Wendy CozenAffiliated withNorris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California
    • , Yolanda BenaventeAffiliated withUnit of Infections and Cancer, Cancer Epidemiology Research Programme, Institut Català d’Oncologia, IDIBELL
    • , Casey PalmersAffiliated withDivision of Environmental Health Sciences, School of Public Health, University of California, Berkeley
    • , Elizabeth A. HollyAffiliated withDepartment of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco
    • , Joshua N. SampsonAffiliated withDivision of Cancer Epidemiology and Genetics, National Cancer Institute
    • , Nathaniel RothmanAffiliated withDivision of Cancer Epidemiology and Genetics, National Cancer Institute
    • , Bruce K. ArmstrongAffiliated withSchool of Public Health, University of Sydney
    • , Lindsay M. MortonAffiliated withDivision of Cancer Epidemiology and Genetics, National Cancer Institute

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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.

Keywords

Non-Hodgkin lymphoma Gene environment interaction Cigarette smoking N-acetyltransferase Follicular lymphoma