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Tobacco smoking and alcohol consumption have not been clearly related to the risk of non-Hodgkin lymphoma (NHL), and the impact of these two factors on survival of NHL patients has received little attention. Cases were 268 subjects with incident histologically-confirmed NHL, admitted as inpatients to the Division of Medical Oncology, between 1983 and 2002. These individuals were enrolled as cases in case-control studies conducted at the same institution over the same period. For all patients clinical (histological subtype, major prognostic factors and treatment) and epidemiological data (smoking and drinking habits) were available. Survival analysis was performed using Kaplan-Meier methods. Hazard ratio (HR) was estimated by Cox proportional hazard model. Compared to never smokers, patients who smoked ≥20 cigarettes/day had higher risks of death (HR = 1.70, 95% confidence interval (CI): 1.06–2.73) and lower survivals at 5 years (60 and 46%, respectively). Likewise, patients who drunk ≥4 drinks/day showed 1.69-fold higher probability of death (95% CI: 1.04–2.76) in comparison to drinkers of <2 drinks/day (5-year survival: 47 and 67%, respectively). When combining exposure to alcohol and tobacco, no excess of death emerged in light drinkers (<4 drinks/day), irrespective of their smoking habits, but higher risks of death emerged among heavy drinkers. In the present study, heavy tobacco smoking, and particularly, heavy alcohol drinking were associated with poor survival in NHL patients. Our findings strongly encourage physicians to advice NHL patients to stop smoking and diminish alcohol consumption to obtain improvements in the course of NHL.