Body mass index, leptin and leptin receptor polymorphisms, and non-hodgkin lymphoma.
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.
Skibola
Christine F
CF
Division of Environmental Health Sciences, School of Public Health, 140 Earl Warren Hall, University of California, Berkeley, CA 94720-7360, USA. chrisfs@berkeley.edu
Holly
Elizabeth A
EA
Forrest
Matthew S
MS
Hubbard
Alan
A
Bracci
Paige M
PM
Skibola
Danica R
DR
Hegedus
Christine
C
Smith
Martyn T
MT
D000328:Adult; D017677:Age Distribution; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D015992:Body Mass Index; D002140:California / Q000453:epidemiology; D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D020738:Leptin / Q000235:genetics*; D016015:Logistic Models; D008228:Lymphoma, Non-Hodgkin / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000235:genetics*; D054411:Receptors, Leptin; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D017678:Sex Distribution
D014408:Biomarkers, Tumor; C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin