leptin and Lymphoma--Non-Hodgkin

In an era of rapidly increasing prevalence of human obesity and associated health problems, leptin gene polymorphisms have drawn much attention in biomedical research. Leptin gene polymorphisms have furthermore drawn much attention from animal scientists for their possible roles in economically important production and reproduction traits. Of the polymorphisms reported for exonic, intronic, and promoter regions of the leptin gene, 16 have been included in association studies in humans, 19 in cattle, and 6 (all exonic or intronic) in pigs. In humans, associations have been found with overweight or (early-onset) obesity, non-insulin-dependent diabetes mellitus, prostate cancer, and non-Hodgkin's lymphoma. In cattle, associations have been found with feed intake, milk yield traits, carcass traits, and reproduction-related traits, and in pigs with feed intake, average daily gain, carcass traits (backfat/leanness), and reproduction performance traits. Many of the polymorphisms were only included in a limited number of association studies, or the phenotypes studied varied largely for a given polymorphism between studies. Therefore, many of the associations found for these polymorphisms need to be confirmed in future studies before firm conclusions can be drawn.

Topics: Animals; Cattle; Diabetes Mellitus, Type 2; DNA, Complementary; Exons; Humans; Introns; Leptin; Lymphoma, Non-Hodgkin; Male; Obesity; Phenotype; Polymorphism, Genetic; Promoter Regions, Genetic; Prostatic Neoplasms; Swine

Non-Hodgkin's lymphoma (NHL) has been widely reported to be associated with autoimmune and pro-inflammatory response, and genetic polymorphisms of candidate genes involved in autoimmune and pro-inflammatory response may influence the survival and prognosis of NHL patients. To evaluate the role of such genetic variations in prognosis of NHL, we conducted this study in a Chinese population.. We used the TaqMan assay to genotype six single nucleotide polymorphisms (SNPs) (TNF rs1799964T>C, LTA rs1800683G>A, IL-10 rs1800872T>G, LEP rs2167270G>A, LEPR rs1327118C>G, TNFAIP8 rs1045241C>T) for 215 NHL cases. Kaplan-Meier analysis was performed to compare progression free survival among two common genotypes. Cox proportional hazard models were used to identify independent risk factors.. We observed that LTA rs1800683G>A was significantly associated with risk of progression or relapse in NHL patients (HR = 1.63, 95%CI = 1.06-2.51; P = 0.028), particularly in Diffuse large B cell lymphoma (DLBCL) cases (HR = 1.50, 95%CI = 1.10-2.04, P = 0.01). Both univariate and multivariate Cox regression analysis showed that in DLBCL patients, Ann Arbor stage III/IV, elevated LDH level before treatment and LTA rs1800683 AA genotype carrier were independent risk factors for progression or relapse. While in NK/T cell lymphoma, Ann Arbor stage III/IV and elevated β2-MG level before treatment indicated poorer prognosis.. The polymorphism of LTA rs1800683G>A contributes to NHL prognosis in a Chinese population. Further large-scale and well-designed studies are needed to confirm these results.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Apoptosis Regulatory Proteins; China; Cyclophosphamide; Disease Progression; Disease-Free Survival; Doxorubicin; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genotyping Techniques; Humans; Interleukin-10; Kaplan-Meier Estimate; Leptin; Lymphoma, Non-Hodgkin; Lymphotoxin-alpha; Male; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local; Polymorphism, Single Nucleotide; Prednisone; Prognosis; Receptors, Leptin; Risk Factors; Treatment Outcome; Tumor Necrosis Factor-alpha; Vincristine; Young Adult

Because immune dysfunction is thought to underlie the development of non-Hodgkin lymphoma (NHL), obesity and chronic inflammation may be involved in its etiology. We examined the association of prediagnostic inflammatory markers and adipokines with NHL risk.. We conducted a nested case-control analysis (272 cases and 541 matched controls) within the Multiethnic Cohort. Luminex technology was used to measure a 10-plex panel of cytokines, ELISA assays for adipokines, and an autoanalyzer for C-reactive protein (CRP). ORs and 95% confidence intervals (CI) for tertiles of analytes were estimated by conditional logistic regression.. After a median time of 2.7 years from phlebotomy to diagnosis, interleukin (IL)-10 was significantly related to NHL risk (ORT3 vs. T1 = 3.07; 95%CI, 2.02-4.66; Ptrend < 0.001). TNF-α and IL-8 showed borderline elevated risks, whereas IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, and CRP were not associated with NHL. Leptin but not adiponectin was related to NHL risk (ORT3 vs. T1 = 0.48; 95%CI, 0.30-0.76; Ptrend < 0.001). Adjustment for body mass index did not substantially affect the risk estimates. Stratification by subtype indicated significant associations with IL-10 and leptin for follicular but not for diffuse large B-cell lymphoma. Excluding cases diagnosed less than 1 year after phlebotomy attenuated all associations.. IL-10 was the only cytokine and leptin the only adipokine associated with NHL, but due to the short follow-up time, preclinical effects cannot be excluded.. Although markers of inflammation and adiposity may provide new insights into the etiology of NHL, they need to be assessed many years before clinical diagnosis.

Topics: Adiposity; Aged; Biomarkers, Tumor; Case-Control Studies; Cytokines; Ethnicity; Female; Humans; Inflammation; Leptin; Lymphoma, Non-Hodgkin; Male; Middle Aged; Obesity; Prognosis; Prospective Studies; Risk Factors

A number of clinical studies conducted in adults have demonstrated the prognostic significance of angiogenic factors in malignancies, however, only a limited number of studies have been conducted in children. The aim of this study was to determine serum vascular endothelial growth factor (VEGF), endostatin, and leptin levels in children with lymphoma and to investigate whether these factors provide prognostic information.. Serum samples from 36 children with lymphoma (non-Hodgkin lymphoma (NHL) N = 21, Hodgkin lymphoma (HL) N = 15) were collected at diagnosis and during remission. Serum samples were also collected from 18 healthy children as the control group. Serum VEGF and endostatin levels were quantified by using enzyme-linked immunosorbent assay (ELISA) and serum leptin by immunoradiometric assay.. The serum VEGF levels were found elevated in patients compared to controls (P = 0.033), while endostatin and leptin levels were lower in patients than in controls (endostatin, 43.9 ± 5.8 ng/ml vs. 123.6 ± 13.5 ng/ml, P < 0.001; leptin, 5 ± 1.5 ng/ml vs. 6.7 ± 1.2 ng/ml, P = 0.013). VEGF levels declined (pre, 151.6 ± 55.9 pg/ml vs. post, 16.2 ± 7.9 pg/ml, P = 0.041), while endostatin and leptin levels increased in patients who achieved remission (33 of 36 patients) when compared to pre-treatment levels (endostatin pre, 43.1 ± 5.9 ng/ml vs. post, 65.9 ± 6.8 ng/ml, P = 0.047; leptin, pre, 5.3 ± 1.6 ng/ml vs. post, 9.8 ± 2.7 ng/ml, P = 0.012). Serum VEGF, endostatin, and leptin levels were not predictive of survival.. Serial measurement of serum VEGF, endostatin, and leptin levels could potentially be used to predict response to treatment or progressive disease in children with lymphoma.

Topics: Angiogenesis Inhibitors; Child; Disease-Free Survival; Endostatins; Female; Hodgkin Disease; Humans; Leptin; Lymphoma, Non-Hodgkin; Male; Prognosis; Survival Rate; Vascular Endothelial Growth Factor A

To our knowledge, this is the first study exploring the association of childhood non-Hodgkin's lymphoma (NHL) with serum adiponectin and leptin levels in a nationwide case-control series. In addition, expression of adiponectin receptors in NHL specimens was assessed, and the association between adipokines and childhood NHL survival and prognosis was examined.. We studied 121 incident childhood (0 to 14 years) NHL cases registered in the Nationwide Registry for Childhood Hematological Malignancies (1996 to 2006) and an equal number of matched controls, for whom sociodemographic, lifestyle, prenatal characteristics, and fasting blood serums were collected. Serum adiponectin and leptin levels were determined. Immunohistochemisty for adiponectin receptors expression was performed on commercially available adult NHL specimens (n = 30) and in a subset of childhood NHL cases (n = 6) that were available. Summary statistics, multiple conditional logistic regression analyses, and survival analysis were performed.. Higher serum adiponectin, but not leptin, levels were independently associated with childhood NHL (odds ratio, 1.82; 95% CI, 1.30 to 2.56), after adjusting for obesity and established risk factors. Higher adiponectin levels at diagnosis were positively associated with relapse and poor survival, but hormone levels did not differ among NHL subtypes. Adiponectin receptors 1 and 2 were present in 90% and 57% of adult samples and in 83% and 100% of childhood NHL samples, respectively.. Elevated serum adiponectin, but not leptin, levels are independently associated with childhood NHL and poor prognosis. Adiponectin receptors are expressed in NHL, suggesting that adiponectin may represent not only a potential clinically significant diagnostic and prognostic marker but also a molecule that may be implicated in NHL pathogenesis.

Topics: Adipokines; Adiponectin; Adolescent; Adult; Case-Control Studies; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Leptin; Lymphoma, Non-Hodgkin; Prognosis; Receptors, Adiponectin; Survival Analysis

A population-based case-control study of lymphomas in England collected height and weight details from 699 non-Hodgkin's lymphoma (NHL) cases and 914 controls. Obesity, defined as a body mass index (BMI) over 30 kg m(-2) at five years before diagnosis,, was associated with an increased risk of NHL (OR = 1.5, 95% CI 1.1-2.1). The excess was most pronounced for diffuse large B-cell lymphoma (OR = 1.9, 95% CI 1.3-2.8). Genetic variants in the leptin (LEP 19G > A, LEP -2548G > A) and leptin receptor genes (LEPR 223Q > R), previously shown to modulate NHL risk, as well as a polymorphism in the energy regulatory gene adiponectin (APM1 276G>T), were investigated. Findings varied with leptin genotype, the risks being decreased with LEP 19AA (OR = 0.7, 95% CI 0.5-1.0) and increased with LEP -2548GA (OR = 1.3, 95% CI 1.0-1.7) and -2548AA (OR = 1.4, 95% CI 1.0-1.9), particularly for follicular lymphoma. These genetic findings, which were independent of BMI, were stronger for men than women.

Topics: Adolescent; Adult; Base Sequence; Case-Control Studies; DNA Primers; Energy Metabolism; Homeostasis; Humans; Leptin; Lymphoma, Non-Hodgkin; Middle Aged; Obesity; Polymorphism, Genetic; Receptors, Cell Surface; Receptors, Leptin

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.

Topics: Adult; Age Distribution; Aged; Biomarkers, Tumor; Body Mass Index; California; Case-Control Studies; Confidence Intervals; Female; Genetic Predisposition to Disease; Humans; Incidence; Leptin; Logistic Models; Lymphoma, Non-Hodgkin; Male; Middle Aged; Odds Ratio; Polymorphism, Genetic; Prognosis; Receptors, Cell Surface; Receptors, Leptin; Retrospective Studies; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Sex Distribution

In patients with cancers progressive reduction of body mass is frequently recent. Pathogenesis of cachexia in patients with cancer is multifactorial. Such factors as cytokines, peptides relieved by tumor mass and different forms of treatment as radio or chemotherapy may play a major role in the pathogenesis of cachexia in patients with cancer. The aim of this study was to assess the relationship between body fat and lean mass and plasma leptin, NPY and TNF concentrations in patients with cancer of oral cavity and pharynx, cancer of larynx and non-Hodgkin lymphoma (NIL). 30 patients (10 with cancer of oral cavity and pharynx, 10 with cancer of larynx and 10 with non-Hodgkin lymphoma) were enrolled into this study. Mean age of all cancer patients was 50 +/- 2.9 years (from 18 to 76 years). The control group consisted of 29 healthy subjects with a means age 48 +/- 3.5 years (from 18 to 75 years), properly chosen according to the body weight, BMI, gender and age as above mentioned groups of patients with cancer. In control and study groups body fat and not-fat mass was assessed before and after treatment using the bioelectrical impedance method. Before oncological therapy patients with cancer did not differ from healthy subject with regard to body weight and body mass index. After treatment significant: decrease of body weight, body fat mass and BMI was observed. Serum leptin, NPY and TNF concentrations were analysed in healthy subjects and patients with cancer before and after treatment. Before oncological treatment significantly lower serum leptin concentration in comparison to leptinaemia in control group was found. In contrast to serum leptin, NPY serum concentration was similar in patients with cancer and in control subjects. Serum concentration of TNF was significantly higher in patients with cancer in comparison to subjects of control group. After oncological treatment, serum leptin and NPY concentration did not change significantly. In contrast, serum TNF concentration decreased significantly after oncological therapy. From the results obtained in this study we can conclude, that in patients with cancer secretion of leptin is decreased in relation to body fat mass. However, contribution of this hormone to pathogenesis of cancer induced anorexia seems not to proven. From the other side, the role of TNF in pathogenesis of disregulation of leptin secretion seems to be very likely. After chemo or radiotherapy, serum NPY concentration did not change signif

Topics: Adult; Aged; Body Mass Index; Cachexia; Case-Control Studies; Chemotherapy, Adjuvant; Female; Head and Neck Neoplasms; Humans; Leptin; Lymphoma, Non-Hodgkin; Male; Middle Aged; Neuropeptide Y; Radiotherapy, Adjuvant; Tumor Necrosis Factor-alpha