Cancer Causes & Control

, Volume 24, Issue 1, pp 125–134

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. Gibson
  • Karin E. Smedby
  • Christine F. Skibola
  • David W. Hein
  • Susan L. Slager
  • Silvia de Sanjosé
  • Claire M. Vajdic
  • Yawei Zhang
  • Brian C.-H. Chiu
  • Sophia S. Wang
  • Henrik Hjalgrim
  • Alexandra Nieters
  • Paige M. Bracci
  • Anne Kricker
  • Tongzhang Zheng
  • Carol Kolar
  • James R. Cerhan
  • Hatef Darabi
  • Nikolaus Becker
  • Lucia Conde
  • Theodore R. Holford
  • Dennis D. Weisenburger
  • Anneclaire J. De Roos
  • Katja Butterbach
  • Jacques Riby
  • Wendy Cozen
  • Yolanda Benavente
  • Casey Palmers
  • Elizabeth A. Holly
  • Joshua N. Sampson
  • Nathaniel Rothman
  • Bruce K. Armstrong
  • Lindsay M. Morton
Original Paper

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 (pinteraction = 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 

Supplementary material

10552_2012_98_MOESM1_ESM.pdf (34 kb)
Supplementary material 1 (PDF 33 kb)
10552_2012_98_MOESM2_ESM.pdf (35 kb)
Supplementary material 2 (PDF 34 kb)
10552_2012_98_MOESM3_ESM.pdf (36 kb)
Supplementary material 3 (PDF 36 kb)

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Copyright information

© Springer Science+Business Media Dordrecht (outside the USA) 2012

Authors and Affiliations

  • Todd M. Gibson
    • 1
    • 2
  • Karin E. Smedby
    • 3
  • Christine F. Skibola
    • 4
  • David W. Hein
    • 5
  • Susan L. Slager
    • 6
  • Silvia de Sanjosé
    • 7
    • 8
  • Claire M. Vajdic
    • 9
    • 10
  • Yawei Zhang
    • 11
  • Brian C.-H. Chiu
    • 12
  • Sophia S. Wang
    • 13
  • Henrik Hjalgrim
    • 14
  • Alexandra Nieters
    • 15
  • Paige M. Bracci
    • 16
  • Anne Kricker
    • 17
  • Tongzhang Zheng
    • 11
  • Carol Kolar
    • 18
  • James R. Cerhan
    • 6
  • Hatef Darabi
    • 19
  • Nikolaus Becker
    • 20
  • Lucia Conde
    • 4
  • Theodore R. Holford
    • 11
  • Dennis D. Weisenburger
    • 21
  • Anneclaire J. De Roos
    • 22
    • 23
  • Katja Butterbach
    • 20
  • Jacques Riby
    • 4
  • Wendy Cozen
    • 24
  • Yolanda Benavente
    • 7
  • Casey Palmers
    • 4
  • Elizabeth A. Holly
    • 16
  • Joshua N. Sampson
    • 1
  • Nathaniel Rothman
    • 1
  • Bruce K. Armstrong
    • 17
  • Lindsay M. Morton
    • 1
  1. 1.Division of Cancer Epidemiology and GeneticsNational Cancer InstituteBethesdaUSA
  2. 2.Cancer Prevention Fellowship Program, Division of Cancer PreventionNational Cancer InstituteBethesdaUSA
  3. 3.Unit of Clinical Epidemiology, Department of MedicineSolna, Karolinska InstituteStockholmSweden
  4. 4.Division of Environmental Health Sciences, School of Public HealthUniversity of California, BerkeleyBerkeleyUSA
  5. 5.Department of Pharmacology and Toxicology and James Graham Brown Cancer Center, School of MedicineUniversity of LouisvilleLouisvilleUSA
  6. 6.Department of Health Sciences ResearchMayo Clinic College of MedicineRochesterUSA
  7. 7.Unit of Infections and Cancer, Cancer Epidemiology Research ProgrammeInstitut Català d’Oncologia, IDIBELLBarcelonaSpain
  8. 8.CIBER Epidemiologia y Salud PúblicaMadridSpain
  9. 9.Adult Cancer ProgramUniversity of New South WalesSydneyAustralia
  10. 10.Lowy Cancer Research Center, Prince of Wales Clinical SchoolUniversity of New South WalesSydneyAustralia
  11. 11.Yale School of Public HealthYale UniversityNew HavenUSA
  12. 12.Department of Health StudiesUniversity of ChicagoChicagoUSA
  13. 13.Division of Cancer Etiology, Department of Population SciencesBeckman Research Institute and the City of HopeDuarteUSA
  14. 14.Department of Epidemiology ResearchStatens Serum InstitutCopenhagenDenmark
  15. 15.Centre of Chronic ImmunodeficiencyUniversity Medical Center FreiburgFreiburgGermany
  16. 16.Department of Epidemiology and Biostatistics, School of MedicineUniversity of California, San FranciscoSan FranciscoUSA
  17. 17.School of Public HealthUniversity of SydneySydneyAustralia
  18. 18.The Eppley Institute for Research in Cancer and Allied DiseasesUniversity of Nebraska Medical CenterOmahaUSA
  19. 19.Department of Medical Epidemiology and BiostatisticsKarolinska InstituteStockholmSweden
  20. 20.Division of Cancer EpidemiologyGerman Cancer Research CenterHeidelbergGermany
  21. 21.Department of Pathology and MicrobiologyUniversity of Nebraska Medical CenterOmahaUSA
  22. 22.Department of Epidemiology, School of Public Health and Community MedicineUniversity of WashingtonSeattleUSA
  23. 23.Program in Epidemiology, Division of Public Health SciencesFred Hutchinson Cancer Research CenterSeattleUSA
  24. 24.Norris Comprehensive Cancer Center, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA

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