Obesity and neoplasms of lymphohematopoietic cells.

In countries such as the United States, where aggressive antismoking campaigns have led to a striking decrease in the fraction of the population who are tobacco smokers, obesity is an unwanted replacement as a preventable factor that increases the risk of cancer in multiple tissues, including the marrow. In a report of August 2016, the International Agency for Research on Cancer (IARC) Handbook Working Group summarized the relative risk of cancer of various tissues as a result of body fatness, based on published studies. They found sufficient evidence to ascribe an elevated risk of cancer in 13 tissues to overweight or obesity. Obesity has also been shown to increase the risk of lymphohematopoietic neoplasms. The IARC Working Group reaffirmed the data linking overweight and obesity to the risk of myeloma, the latter neoplasm originating in the transformation of a marrow B-lymphocytic progenitor cell. The evidence for an increased risk of myeloma as a result of overweight and obesity is compelling. Of special interest is whether the precursor of myeloma, essential monoclonal gammopathy (also known as monoclonal gammopathy of unknown significance), has an increased risk of occurrence in obese patients. An initial study indicated that it did, whereas a recent study has challenged that finding. The reason that this relationship is of particular interest is that it speaks to the question of the mechanism by which the consequences of obesity act. Obesity could be inductive, that is the metabolic, endocrine, and inflammatory effects of excess adipose tissue might contribute directly to the acquisition of oncogenic mutations during DNA replication or repair in the process of cell division and, thereby, establish a neoplastic clone. Alternatively, the varied and influential metabolic effects of fat tissue could act to select an established, but dormant, clone to undergo evolution to a malignancy. If essential monoclonal gammopathy is not increased in prevalence in overweight and obese subjects, this finding could be interpreted as favoring the selection hypothesis, at least as it applies to myelomagenesis.