Table_1_Environmental and Other Extrinsic Risk Factors Contributing to the Pathogenesis of Cutaneous T Cell Lymphoma (CTCL).DOCX

The applications of disease cluster investigations in medicine have developed rather rapidly in recent decades. Analyzing the epidemiology of non-random aggregation of patients with a particular disease fostered identification of environmental and external exposures as disease triggers and promoters. Observation of patient clusters and their association with nearby exposures, such as Dr. John Snow's astute mapping analysis in the mid-1800's, which revealed proximity of cholera patients in London to a contaminated water pump infected with Vibrio cholerae, have paved the way for the field of epidemiology. This approach enabled the identification of triggers for many human diseases including infections and cancers. Cutaneous T-cell lymphomas (CTCL) represent a group of non-Hodgkin lymphomas that primarily affect the skin. The detailed pathogenesis by which CTCL develops remains largely unknown. Notably, non-random clustering of CTCL patients was reported in several areas worldwide and this rare malignancy was also described to affect multiple members of the same family. These observations indicate that external factors are possibly implicated in promoting CTCL lymphomagenesis. Here, we review the epidemiology of CTCL worldwide and the clinical characteristics of CTCL patients, as revealed by global epidemiological data. Further, we review the known risk factors including sex, age, race as well as environmental, infectious, iatrogenic and other exposures, that are implicated in CTCL lymphomagenesis and discuss conceivable mechanisms by which these factors may trigger this malignancy.