Cigarette smoking and risk of Hodgkin lymphoma: a population-based case-control study.
BACKGROUND
Studies have inconsistently reported an association between tobacco smoking and Hodgkin lymphoma (HL) risk. The conflicting finding may reflect etiologic heterogeneity between HL subtypes, warranting further characterization of the relationship.


METHODS
We collected information on tobacco-smoking habits in 586 classic HL cases and 3,187 population controls in a Danish-Swedish case-control study. HL EBV status was established for 499 cases by standard techniques. Odds ratios (OR) for an association with cigarette smoking were calculated by logistic regression for HL overall and stratified by age, sex, major histology subtypes, and tumor EBV status, adjusting for known confounders.


RESULTS
Compared with never smokers, current cigarette smokers were at an increased overall HL risk [adjusted OR, 1.57; 95% confidence interval (95% CI), 1.22-2.03]. The association was strongest for EBV-positive HL (adjusted OR, 2.36; 95% CI, 1.51-3.71), but also applied to EBV-negative HL (adjusted OR, 1.43; 95% CI, 1.05-1.97; P(homogeneity EBV-pos) versus P(homogeneity EBV-neg) = 0.04). The association did not vary appreciably by age, sex, or histologic subtype, the apparent EBV-related difference present in all strata. There was no evidence of a dose-response pattern, whether by age at smoking initiation, daily cigarette consumption, number of years smoking, or cumulative number of cigarettes smoked. Similar results were obtained in analyses using non-HL patients (n = 3,055) participating in the founding study as comparison group.


CONCLUSIONS
The observed association between cigarette smoking and HL risk is consistent with previous findings and biologically credible. Although not easily dismissed as an artifact, the limited evidence of a dose-response pattern renders the overall evidence of causality weak.
Hjalgrim
Henrik
H
Department of Epidemiology Research, Statens Serum Institut, University of Copenhagen, Artillerivej 5, DK-2300 Copenhagen S, Denmark. hhj@ssi.dk
Ekström-Smedby
Karin
K
Rostgaard
Klaus
K
Amini
Rose-Marie
RM
Molin
Daniel
D
Hamilton-Dutoit
Stephen
S
Schöllkopf
Claudia
C
Chang
Ellen T
ET
Ralfkiaer
Elisabeth
E
Adami
Hans-Olov
HO
Glimelius
Bengt
B
Melbye
Mads
M
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D016022:Case-Control Studies; D015986:Confounding Factors, Epidemiologic; D020031:Epstein-Barr Virus Infections / Q000150:complications; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006689:Hodgkin Disease / Q000145:classification / Q000209:etiology* / Q000821:virology; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000145:classification / Q000209:etiology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors