Obesity and Leptin Receptor Polymorphisms are Associated with Non-Hodgkin Lymphoma

Martyn Smith, Ph.D.
University of California School of Public Health, Berkeley
P30ES01896

Background: The popular press and the medical literature are full of accounts of the "Obesity Epidemic" in the United States. Obesity has definitively been increasing in industrialized countries over the past few decades. This increase has been attributed to life-style changes such as decreased physical activity, consumption of high-fat diets, and increased portion sizes.

During this same period the incidence of non-Hodgkin lymphoma (NHL) has also been increasing. NHL has become one of the most commonly diagnosed cancers in the Western world. The major subtypes of NHL in the U.S. are diffuse large cell lymphoma (DLCL) and follicular lymphoma (FL). DLCL has increased the most with some estimates suggesting a doubling over the past few decades. Reasons for this increase are poorly understood and risk factors for NHL subtypes have not been identified.

These NIEHS-supported investigators conducted a population-based case-control study with 1,593 NHL patients and 2,515 controls to determine whether there was an association between obesity and NHL.

Advance: In this study, obesity was defined as a body mass index greater than 30. People who were obese were up to three times more likely to develop NHL than persons with a body mass index between 20 and 25 (Body mass index is calculated as weight in kilograms divided by height in meters squared). Obesity-related genetic factors including polymorphisms in the leptin gene and its receptor were investigated in DNA from a selection of patients and controls. Leptin is a hormone produced in fat cells that is involved in the regulation of food intake and modulates immune and inflammatory responses. The researchers were able to identify specific polymorphisms that were also associated with increased risk for NHL.

Implications: Results from the epidemiologic and genetic analyses suggest that there is an association between obesity and NHL. Genetic interactions between leptin and its receptor may promote immune dysfunction associated with obesity and NHL. The results also suggest that the emerging obesity epidemic is at least consistent and may be at least partly responsible for the increasing incidence of NHL. The authors conclude that since "obesity and lymphoma are becoming increasingly more prevalent throughout the world, the observed associations may have important public health implications."

Citation: Skibola CF, Holly EA, Forrest MS, Hubbard A, Bracci PM, Skibola DR, Hegedus C, Smith MT. Body mass index, leptin and leptin receptor polymorphisms, and non-Hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev. 2004 May;13(5):779-86.