The Relationship between Cigarette Smoking and the Risk of Leukaemia: A Review of Epidemiological Evidence and Biological Mechanisms

Leukaemia comprises a number of haematological malignancies, being marked by the uncontrolled growth of abnormal blood-forming cells and as a result interfering with the normal production of blood cells. This review looks at the connection between cigarette smoking and leukaemia, with an emphasis on the epidemiological evidence and on the biological mechanisms by which tobacco smoke might lead to the development of the disease. Cigarette smoke includes a variety of harmful and carcinogenic substances such as benzene, tobacco-specific nitrosamines and polycyclic aromatic hydrocarbons. These substances can cause oxidative stress, damage to DNA, chromosomal abnormalities and genetic and epigenetic changes in haematopoietic stem and progenitor cells. Such alterations may interfere with normal cell differentiation, proliferation and apoptosis and could thus play a role in the development of leukaemia. The evidence reviewed shows that cigarette smoking is most consistently linked to acute myeloid leukaemia (AML), with various studies finding a higher risk among both current and former smokers. The evidence relating to acute lymphoblastic leukaemia (ALL), chronic myeloid leukaemia (CML) and chronic lymphocytic leukaemia (CLL) is less consistent, differing from study to study and according to the subtype of disease. The bone marrow toxicity related to benzene and the disruption of the bone marrow microenvironment offer plausible biological explanations for the associations observed. In general, the available literature supports an association between cigarette smoking and leukaemia, especially with regard to AML, even though more research is required to clarify the less well-established relationships. Continued efforts to prevent and help people to stop smoking should be considered major public health goals.