Chronic lymphocytic leukaemia: an overview of aetiology in light of recent developments in classification and pathogenesis

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Abstract
Summary: This overview of the epidemiology of chronic lymphocytic leukaemia (CLL) summarizes the evolution of classification and coding systems and describes the intersection of pathogenesis and aetiology. The role of the putative precursor to CLL, monoclonal B‐cell lymphocytosis (MBL), is considered, and ideas for future investigations of the MBL‐CLL relationship are outlined. We discuss the epidemiology of CLL, focusing on descriptive patterns and methodological considerations. Postulated risk factors are reviewed including the role of ionizing and non‐ionizing radiation, occupational and environmental chemical exposures, medical conditions and treatments, and lifestyle and genetic factors. We conclude by raising key questions that need to be addressed to advance our understanding of CLL aetiology. Recommendations for future epidemiological studies are given, including the standardization of reporting of CLL across cancer registries, the clarification of the natural history of MBL, and the circumvention of the methodological shortcomings of prior epidemiological investigations in relation to radiation, chemical exposures and infectious agents.