title: Smoking, variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2), and risk of non-Hodgkin lymphoma: a pooled analysis within the InterLymph consortium.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd., Bethesda, MD 20892, USA. gibsontm@mail.nih.gov
authors.forename: Todd M
authors.initials: TM
authors.lastname: Gibson
authors.forename: Karin E
authors.initials: KE
authors.lastname: Smedby
authors.forename: Christine F
authors.initials: CF
authors.lastname: Skibola
authors.forename: David W
authors.initials: DW
authors.lastname: Hein
authors.forename: Susan L
authors.initials: SL
authors.lastname: Slager
authors.forename: Silvia
authors.initials: S
authors.lastname: de Sanjosé
authors.forename: Claire M
authors.initials: CM
authors.lastname: Vajdic
authors.forename: Yawei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Brian C-H
authors.initials: BC
authors.lastname: Chiu
authors.forename: Sophia S
authors.initials: SS
authors.lastname: Wang
authors.forename: Henrik
authors.initials: H
authors.lastname: Hjalgrim
authors.forename: Alexandra
authors.initials: A
authors.lastname: Nieters
authors.forename: Paige M
authors.initials: PM
authors.lastname: Bracci
authors.forename: Anne
authors.initials: A
authors.lastname: Kricker
authors.forename: Tongzhang
authors.initials: T
authors.lastname: Zheng
authors.forename: Carol
authors.initials: C
authors.lastname: Kolar
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.forename: Hatef
authors.initials: H
authors.lastname: Darabi
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Becker
authors.forename: Lucia
authors.initials: L
authors.lastname: Conde
authors.forename: Theodore R
authors.initials: TR
authors.lastname: Holford
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Weisenburger
authors.forename: Anneclaire J
authors.initials: AJ
authors.lastname: De Roos
authors.forename: Katja
authors.initials: K
authors.lastname: Butterbach
authors.forename: Jacques
authors.initials: J
authors.lastname: Riby
authors.forename: Wendy
authors.initials: W
authors.lastname: Cozen
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Benavente
authors.forename: Casey
authors.initials: C
authors.lastname: Palmers
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Holly
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Sampson
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Armstrong
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Morton
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D014644:Genetic Variation / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008228:Lymphoma, Non-Hodgkin / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology; D055815:Young Adult
chemical_list: D007527:Isoenzymes; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; C478900:NAT2 protein, human