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

Abstract

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.

Clustering of cutaneous T‐cell lymphoma is associated with increased levels of the environmental toxins benzene and trichloroethylene in the state of Georgia

“…6 Clues pointing to attribution of environmental exposure include the concomitant rise in CTCL cases with industrial expansion, increased incidence in nonblood-related relatives, and known associations of occupational chemicals with other hematologic malignancies. [7][8][9] Clustering has been identified in several studies across the globe, including Sweden, 10 Canada, 11,12 Pittsburgh, Pennsylvania, 13 and Texas. 5,14 The analysis in Texas found 3 communities in metropolitan Houston with rates of CTCL that were between 5 and 20 times higher than the expected population rate.…”

“…Although approximately 50% of the increase in CTCL can be attributed to increased diagnosis and reporting of these cancers, this does not fully account for the population trends . Clues pointing to attribution of environmental exposure include the concomitant rise in CTCL cases with industrial expansion, increased incidence in nonblood‐related relatives, and known associations of occupational chemicals with other hematologic malignancies . Clustering has been identified in several studies across the globe, including Sweden, Canada, Pittsburgh, Pennsylvania, and Texas .…”

Identification of significant geographic clustering of polycythemia vera cases in Montreal, Canada

“…Demographic and geographic data were obtained from the Canadian Cancer Registry (CCR), Le Registre Québécois du Cancer (LRQC), and the Canadian Vital Statistics (CVS) databases, as described previously. 13,14,[16][17][18][19][20][21][22][23][24][25][26] The CCR is a national database of cancer patients from 12 Canadian provinces and territories (excluding Quebec) who were diagnosed with primary tumors between 1992 and 2014. The LRQC database was used to obtain corresponding data for patients residing in Quebec.…”

MicroRNAs in the Pathogenesis, Diagnosis, Prognosis and Targeted Treatment of Cutaneous T-Cell Lymphomas

“…Despite intense research efforts in recent years, the pathogenesis of CTCL still remains poorly understood. Genetic, epigenetic, and environmental factors have all been proposed to be implicated in CTCL [1,4,5]. To date, no studies have identified overarching mutational drivers explaining the pathogenesis of this cancer; however, genetic aberrations may be important in a subset of patients, but are not sufficient to explain the full complexity of CTCL's pathology [6].…”

“…A comprehensive study, taking advantage of the Danish cohort of twins, suggested that CTCL has very few heritable components, and several lines of evidence indicate that environmental factors may play a promoting or even initiating role in the carcinogenesis of CTCL [5,45]. Accordingly, it may be speculated that exogeneous factors including drugs, pesticides, and bacterial toxins may promote disease progression [5].…”