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 CondeTheodore 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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)125-134
Number of pages10
JournalCancer Causes and Control
Volume24
Issue number1
DOIs
StatePublished - Jan 2013

Fingerprint

Non-Hodgkin's Lymphoma
Smoking
Acetyltransferases
Follicular Lymphoma
Odds Ratio
Confidence Intervals
Enzymes
Logistic Models
Phenotype
N-acetyltransferase 1
Acetylation
Carcinogens
Tobacco
Case-Control Studies
Lymphoma
Epidemiology
Joints
Genes

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Smoking, variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2), and risk of non-Hodgkin lymphoma : A pooled analysis within the InterLymph consortium. / Gibson, Todd M.; Smedby, Karin E.; Skibola, Christine F.; Hein, David W.; Slager, Susan L; De Sanjosé, Silvia; Vajdic, Claire M.; Zhang, Yawei; Chiu, Brian C H; Wang, Sophia S.; Hjalgrim, Henrik; Nieters, Alexandra; Bracci, Paige M.; Kricker, Anne; Zheng, Tongzhang; Kolar, Carol; Cerhan, James R; Darabi, Hatef; Becker, Nikolaus; Conde, Lucia; Holford, Theodore R.; Weisenburger, Dennis D.; De Roos, Anneclaire J.; Butterbach, Katja; Riby, Jacques; Cozen, Wendy; Benavente, Yolanda; Palmers, Casey; Holly, Elizabeth A.; Sampson, Joshua N.; Rothman, Nathaniel; Armstrong, Bruce K.; Morton, Lindsay M.

In: Cancer Causes and Control, Vol. 24, No. 1, 01.2013, p. 125-134.

Research output: Contribution to journalArticle

Gibson, TM, Smedby, KE, Skibola, CF, Hein, DW, Slager, SL, De Sanjosé, S, Vajdic, CM, Zhang, Y, Chiu, BCH, Wang, SS, Hjalgrim, H, Nieters, A, Bracci, PM, Kricker, A, Zheng, T, Kolar, C, Cerhan, JR, Darabi, H, Becker, N, Conde, L, Holford, TR, Weisenburger, DD, De Roos, AJ, Butterbach, K, Riby, J, Cozen, W, Benavente, Y, Palmers, C, Holly, EA, Sampson, JN, Rothman, N, Armstrong, BK & Morton, LM 2013, '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 and Control, vol. 24, no. 1, pp. 125-134. https://doi.org/10.1007/s10552-012-0098-4
Gibson, Todd M. ; Smedby, Karin E. ; Skibola, Christine F. ; Hein, David W. ; Slager, Susan L ; De Sanjosé, Silvia ; Vajdic, Claire M. ; Zhang, Yawei ; Chiu, Brian C H ; Wang, Sophia S. ; Hjalgrim, Henrik ; Nieters, Alexandra ; Bracci, Paige M. ; Kricker, Anne ; Zheng, Tongzhang ; Kolar, Carol ; Cerhan, James R ; Darabi, Hatef ; Becker, Nikolaus ; Conde, Lucia ; Holford, Theodore R. ; Weisenburger, Dennis D. ; De Roos, Anneclaire J. ; Butterbach, Katja ; Riby, Jacques ; Cozen, Wendy ; Benavente, Yolanda ; Palmers, Casey ; Holly, Elizabeth A. ; Sampson, Joshua N. ; Rothman, Nathaniel ; Armstrong, Bruce K. ; Morton, Lindsay M. / Smoking, variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2), and risk of non-Hodgkin lymphoma : A pooled analysis within the InterLymph consortium. In: Cancer Causes and Control. 2013 ; Vol. 24, No. 1. pp. 125-134.
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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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T2 - A pooled analysis within the InterLymph consortium

AU - Gibson, Todd M.

AU - Smedby, Karin E.

AU - Skibola, Christine F.

AU - Hein, David W.

AU - Slager, Susan L

AU - De Sanjosé, Silvia

AU - Vajdic, Claire M.

AU - Zhang, Yawei

AU - Chiu, Brian C H

AU - Wang, Sophia S.

AU - Hjalgrim, Henrik

AU - Nieters, Alexandra

AU - Bracci, Paige M.

AU - Kricker, Anne

AU - Zheng, Tongzhang

AU - Kolar, Carol

AU - Cerhan, James R

AU - Darabi, Hatef

AU - Becker, Nikolaus

AU - Conde, Lucia

AU - Holford, Theodore R.

AU - Weisenburger, Dennis D.

AU - De Roos, Anneclaire J.

AU - Butterbach, Katja

AU - Riby, Jacques

AU - Cozen, Wendy

AU - Benavente, Yolanda

AU - Palmers, Casey

AU - Holly, Elizabeth A.

AU - Sampson, Joshua N.

AU - Rothman, Nathaniel

AU - Armstrong, Bruce K.

AU - Morton, Lindsay M.

PY - 2013/1

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N2 - 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.

AB - 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.

KW - Cigarette smoking

KW - Follicular lymphoma

KW - Gene environment interaction

KW - N-acetyltransferase

KW - Non-Hodgkin lymphoma

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