Body Mass Index, Leptin and Leptin Receptor Polymorphisms, and Non-Hodgkin Lymphoma

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 13; no. 5; pp. 779 - 786
• Main Authors: SKIBOLA, Christine F, HOLLY, Elizabeth A, FORREST, Matthew S, HUBBARD, Alan, BRACCI, Paige M, SKIBOLA, Danica R, HEGEDUS, Christine, SMITH, Martyn T
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.05.2004
• Subjects: Adult; Age Distribution; Aged; Biological and medical sciences; Biomarkers, Tumor - analysis; Body Mass Index; California - epidemiology; Case-Control Studies; Confidence Intervals; Female; Genetic Predisposition to Disease; Hematologic and hematopoietic diseases; Humans; Incidence; Leptin - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Logistic Models; Lymphoma, Non-Hodgkin - epidemiology; Lymphoma, Non-Hodgkin - genetics; Male; Medical sciences; Middle Aged; Odds Ratio; Polymorphism, Genetic; Prognosis; Receptors, Cell Surface - genetics; Receptors, Leptin; Retrospective Studies; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Sex Distribution; United States; North America; America; California; Human; Obesity; Genetic variability; Nutrition disorder; Genotype; Malignant hemopathy; Non Hodgkin lymphoma; Epidemiology; Body mass index; Cancerology; Gene; Lymphoproliferative syndrome; Leptin; Risk factor; Genetics; Public health; Nutritional status; Polymorphism; Biological receptor
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.779.13.5

In a population-based case-control study, obesity was associated with elevated odds ratios (ORs) for non-Hodgkin lymphoma (NHL), and the two major subtypes, diffuse large cell (DLCL) and follicular lymphoma (FL). Those who were obese (body mass index ≥ 30) were up to three times more likely to develop NHL or its major subtypes than persons with body mass index of 20 to <25. Obesity-related genetic factors including common polymorphisms in the leptin gene ( LEP A19G and G-2548A) and its receptor ( LEPR Q223R) were investigated in DNA available for 376 patients and 805 controls. Leptin is an adipocyte-derived hormone that regulates food intake and modulates immune and inflammatory responses through its receptor. Among those with the LEP 19G allele, an increased risk estimate was found for all NHL [OR = 1.6, confidence interval (CI) 1.1–2.3], DLCL (OR = 1.6, CI 0.86–3.0), and FL lymphoma (OR = 1.9, CI 0.98–3.6). Gene-gene interaction existed between the −G2548A and LEPR Q223R polymorphisms. Specifically, among those with LEPR 223RR, the risk estimate for NHL was increased in LEP −2548GA (OR = 1.7, CI 0.88–3.1) and LEP −2548AA (OR = 2.3,CI 1.1–4.6) relative to LEP −2548GG genotypes. These results suggest that genetic interactions between leptin and its receptor may promote immune dysfunction associated with obesity and NHL and that the emerging obesity epidemic is consistent with the increasing incidence of NHL in developed countries.