Cigarette smoking and risk of Hodgkin lymphoma and its subtypes: a pooled analysis from the International Lymphoma Epidemiology Consortium (InterLymph)

Ann Oncol. 2013 Sep;24(9):2245-55. doi: 10.1093/annonc/mdt218. Epub 2013 Jun 19.


Background: The etiology of Hodgkin lymphoma (HL) remains incompletely characterized. Studies of the association between smoking and HL have yielded ambiguous results, possibly due to differences between HL subtypes.

Patients and methods: Through the InterLymph Consortium, 12 case-control studies regarding cigarette smoking and HL were identified. Pooled analyses on the association between smoking and HL stratified by tumor histology and Epstein-Barr virus (EBV) status were conducted using random effects models adjusted for confounders. Analyses included 3335 HL cases and 14 278 controls.

Results: Overall, 54.5% of cases and 57.4% of controls were ever cigarette smokers. Compared with never smokers, ever smokers had an odds ratio (OR) of HL of 1.10 [95% confidence interval (CI) 1.01-1.21]. This increased risk reflected associations with mixed cellularity cHL (OR = 1.60, 95% CI 1.29-1.99) and EBV-positive cHL (OR = 1.81, 95% CI 1.27-2.56) among current smokers, whereas risk of nodular sclerosis (OR = 1.09, 95% CI 0.90-1.32) and EBV-negative HL (OR = 1.02, 95% CI 0.72-1.44) was not increased.

Conclusion: These results support the notion of etiologic heterogeneity between HL subtypes, highlighting the need for HL stratification in future studies. Even if not relevant to all subtypes, our study emphasizes that cigarette smoking should be added to the few modifiable HL risk factors identified.

Keywords: Epstein–Barr virus; Hodgkin lymphoma; case–control; cigarette smoking; epidemiology; individual patient data meta-analysis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Epstein-Barr Virus Infections / complications
  • Epstein-Barr Virus Infections / epidemiology*
  • Female
  • Herpesvirus 4, Human / isolation & purification
  • Hodgkin Disease / chemically induced
  • Hodgkin Disease / epidemiology*
  • Humans
  • Male
  • Middle Aged
  • Risk
  • Risk Factors
  • Smoking / adverse effects
  • Smoking / epidemiology*
  • Social Class
  • Tobacco Use Disorder / complications
  • Tobacco Use Disorder / epidemiology
  • Young Adult