History of allergies and autoimmune diseases and risk of brain tumors in adults

To explore a possible influence of the immune system in the development of brain tumors, we evaluated the relationship between history of allergies and autoimmune diseases and risk of brain tumors within a large, hospital-based case-control study. Cases (n = 782) were patients recently diagnosed with glioma (n = 489), meningioma (n = 197) or acoustic neuroma (n = 96) at hospitals in Boston, Phoenix and Pittsburgh (USA). Controls (n =799) were patients hospitalized for a variety of nonmalignant conditions and frequency-matched to cases by hospital, age, sex, race/ethnicity and distance of residence from hospital. Research nurses collected data by personal interview of patients. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression. There was a significant inverse association between glioma and history of any allergies (OR = 0.67, 95% CI = 0.52-0.86) or autoimmune diseases (OR = 0.49, 95% CI = 0.35-0.69). No significant associations were evident for meningioma or acoustic neuroma with history of any allergies. An inverse association was observed between meningioma and history of autoimmune diseases (OR = 0.59, 95% CI = 0.38-0.92). There was a suggestion of interaction between allergies and autoimmune diseases on risk of glioma (p = 0.06), with subjects having both conditions being at lowest risk (OR = 0.24, 95% CI = 0.14-0.42). Among the specific conditions, asthma and diabetes showed the most consistent associations (OR = 0.63, 95% CI = 0.43-0.92 and OR = 0.44, 95% CI = 0.27-0.70, respectively). Our results add to evidence that persons with allergies or autoimmune diseases are at reduced risk of glioma. The basis of the associations is not clear, but they might imply a role of immunologic factors in the development of brain tumors. Published 2002 Wiley-Liss, Inc.     

Cigarette smoking and risk of non-Hodgkin's lymphoma--a population-based case-control study.

BACKGROUND: Epidemiologic evidence of an association between tobacco smoking and non-Hodgkin's lymphoma has been conflicting. This may reflect that non-Hodgkin's lymphoma comprises several distinct disease entities with different etiologies, as some studies have indicated an association between smoking and follicular lymphoma. OBJECTIVE: To investigate the association between cigarette smoking and non-Hodgkin's lymphoma risk, overall and by subtype. METHODS: As part of a nationwide Danish-Swedish population-based case-control study, we interviewed 3,055 incident non-Hodgkin's lymphoma patients and 3,187 population controls. All lymphomas were uniformly classified according to the WHO classification. We used unconditional logistic regression to estimate adjusted odds ratios (OR) and 95% confidence intervals (95% CI) for the association between cigarette smoking and risk of non-Hodgkin's lymphoma. RESULTS: Cigarette smoking was not associated with the risk of non-Hodgkin's lymphoma overall (OR, 0.97; 95% CI, 0.87-1.08) nor with the major subgroups such as diffuse large B-cell lymphoma (OR, 0.94; 95% CI, 0.79-1.10), chronic lymphocytic leukemia (OR, 0.86; 95% CI, 0.72-1.02), or follicular lymphoma (OR, 1.03; 95% CI, 0.85-1.24). Female smokers were at a marginally increased risk of follicular lymphoma (OR, 1.41; 95% CI, 1.04-1.92). Men who had ever smoked had a significantly increased risk of T-cell lymphoma (OR, 1.67; 95% CI, 1.11-2.51). No dose-response association with cigarette smoking could be established for any lymphoma subgroup. CONCLUSION: We found little evidence of an association between cigarette smoking and non-Hodgkin's lymphoma risk overall. Although increased risks of follicular lymphoma in female smokers and of T-cell lymphoma in male smokers were suggested, no dose-response relationship was observed, leaving limited support for causality.     

History of allergies and risk of glioma in adults

Epidemiological studies have consistently reported an inverse association between a history of allergic disease and risk of glioma. The reason for this association is unclear, and there is a lack of studies with the detail and size to explore the association in depth. We conducted a UK population-based case-control study with 965 glioma cases and 1,716 controls to investigate glioma risk in relation to allergic disease. Risk was reduced in subjects reporting a history of asthma (odds ratio (OR) = 0.71, 95% confidence interval (CI): 0.54-0.92), hay fever (OR = 0.73, 95% CI: 0.59-0.90), eczema (OR = 0.74, 95% CI: 0.56-0.97) and other allergies (OR = 0.65, 95% CI: 0.47-0.90). Risk was reduced for all the main histological groups. There was no significant trend of risk with age, at the onset of each condition, or the number of conditions reported. Risk reductions were strongest for asthma or hay fever with recent onset. Risk in asthmatic subjects was not related to frequency of use of antiasthmatic drugs, but was significantly reduced for use of antiallergenic medication among subjects with hay fever. The study showed an inverse association of glioma risk with allergic disease. Possible reasons for the association, as well as potential immunological aetiology, include confounding, bias and reverse causality.     

Polymorphisms in immune function genes and risk of non-Hodgkin lymphoma: findings from the New South Wales non-Hodgkin Lymphoma Study

Recent findings suggest that genetic polymorphisms in TNF and IL10 are associated with an increased risk of non-Hodgkin lymphoma (NHL), particularly for diffuse large B-cell lymphoma (DLBCL). To further investigate the contribution of common genetic variation in key cytokine and innate immunity genes to the etiology of NHL, we genotyped participants in a case-control study of NHL conducted in Australia (545 cases, 498 controls). We investigated 36 single nucleotide polymorphisms in IL10, TNF and 21 other immune function genes. We observed an elevated risk of DLBCL with the IL10 -3575T>A polymorphism [TA genotype: odds ratio (OR)=1.32, 95% confidence interval (CI)=0.86-2.02; AA, OR=1.84, 95% CI=1.10-3.08; trend test, P=0.02]. Our most noteworthy TNF finding was an association between -857C>T and a decreased risk of NHL (CT or TT, OR=0.59, 95% CI=0.42-0.84, P=0.003) and particularly follicular lymphoma (OR=0.40, 95% CI=0.23-0.68, P=0.0009). Additionally, TNF -863C>A was associated with an elevated risk of DLBCL (CA, OR=1.45, 95% CI=0.95-2.21; AA, OR=2.06, 95% CI=0.88-4.83; trend test, P=0.02). Our findings offer further evidence that variation in the IL10 and TNF loci influences NHL risk. Additional studies are needed to clarify the genetic and biologic basis for these relationships.     

Risk of malignant lymphoma associated with human herpesvirus-8: a case-control study in Spain

No overall increased risk of lymphoma associated with antibodies to human herpesvirus-8 was found in 526 lymphomas and 599 controls (odds ratio (OR)=1.04, 95% confidence interval (CI)=0.62-1.75); significant increases were noted for 19 lymphoplasmacytic lymphomas (OR=4.47, 95% CI=1.34-14.85) and nine low-grade lymphoma/lymphoma B-cell NOS (OR=5.82, 95% CI=1.07-31.73).     

Is birth weight associated with childhood lymphoma? A meta‐analysis

Several risk factors have been identified for childhood lymphomas. The purpose of this meta-analysis was to synthesize current evidence regarding the association between birth weight with primarily the risk for non-Hodgkin lymphoma (NHL), given its similarity to acute lymphoblastic leukemia, Hodgkin lymphoma (HL) and any category of lymphoma. Two cohort (278,751 children) and seven case-control studies (2,660 cases and 69,274 controls) were included. Effects estimates regarding NHL, HL and any lymphoma were appropriately pooled using fixed or random effects model in two separate analyses: specifically, high was compared to normal or any birth weight. Similarly, low was compared to normal or any birth weight. No statistically significant association was found between high birth weight, as compared to normal birth weight, and risk for NHL plus Burkitt lymphoma (OR = 1.17, 95% CI = 0.76-1.80, random effects), HL (OR = 0.94, 95% CI = 0.64-1.38, fixed effects) or any plus Burkitt lymphoma (OR = 1.09, 95% CI = 0.76-1.56, fixed effects). A null association emerged when low was compared with normal birth weight for NHL plus Burkitt lymphoma (OR = 1.07, 95% CI = 0.71-1.62, random effects), HL (OR = 0.94, 95% CI = 0.54-1.65, fixed effects) or any plus Burkitt lymphoma (OR = 1.02, 95% CI = 0.79-1.33, fixed effects). Accordingly, no association was found when high or low birth weight was compared to any birth weight. Although current evidence suggests no association, birth weight might be a too crude indicator to reveal a genuine association of fetal growth with specific lymphoma categories; hence, there is an emerging need for use of more elaborate proxies, at least those accounting for gestational week.     

Association Between the hsa-mir-27a Variant and Breast Cancer Risk: a Meta-analysis

Introduction: Although a number of studies were published in the past several years on associations betweenhsa-mir-27a and cancer risk, the findings remain conflicting rather than conclusive. To derive a more precise effecton the association between SNP hsa-mir-27a rs895819 and breast cancer risk, we conducted a meta-analysis forthe first time. Materials and Methods: Through retrieval from PubMed for the period up to August 2012, a totalof four studies were identified with 3,287 cases and 4,298 controls for SNP hsa-mir-27a rs895819.We calculatedsummary odds ratio (ORs) and corresponding 95% confidence intervals (CIs) using a fixed effects model (whenthe heterogeneity was absent, P>0.10). Otherwise, the random-effects model was used. Results: We found thathsa-mir-27a rs895819 polymorphism also did not reveal any relationship with breast cancer susceptibility (AGversus AA: OR = 0.98; 95%CI, 0.73-1.32; GG versus AA: OR = 0.86; 95% CI, 0.72-1.03; AG/GG versus AA:OR = 0.92; 95% CI, 0.74-1.14), while significantly decreased risk was found among Europeans in AG versus AAand AG/GG versus AA models tested (AG versus AA: OR = 0.83; 95%CI, 0.72-0.97; GG versus AA: OR = 0.86;95% CI, 0.71-1.05; AG/GG versus AA: OR = 0.84; 95% CI, 0.75-0.94). Conclusion: These findings suggest thathsa-mir-27a rs895819 polymorphism may play an important role in breast cancer development.     

Cigarette smoking and risk of non-Hodgkin lymphoma: a pooled analysis from the International Lymphoma Epidemiology Consortium (interlymph).

BACKGROUND: The International Lymphoma Epidemiology Consortium (InterLymph) provides an opportunity to analyze the relationship between cigarette smoking and non-Hodgkin lymphoma with sufficient statistical power to consider non-Hodgkin lymphoma subtype. The results from previous studies of this relationship have been inconsistent, likely due to the small sample sizes that arose from stratification by disease subtype. To clarify the role of cigarette smoking in the etiology of non-Hodgkin lymphoma, we conducted a pooled analysis of original patient data from nine case-control studies of non-Hodgkin lymphoma conducted in the United States, Europe, and Australia. METHODS: Original data were obtained from each study and uniformly coded. Risk estimates from fixed-effects and two-stage random-effects models were compared to determine the impact of interstudy heterogeneity. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived from unconditional logistic regression models, controlling for study center, age, sex, and race. RESULTS: In our pooled study population of 6,594 cases and 8,892 controls, smoking was associated with slightly increased risk estimates (OR, 1.07; 95% CI, 1.00-1.15). Stratification by non-Hodgkin lymphoma subtype revealed that the most consistent association between cigarette smoking and non-Hodgkin lymphoma was observed among follicular lymphomas (n = 1452). Compared with nonsmokers, current smokers had a higher OR for follicular lymphoma (1.31; 95% CI, 1.12-1.52) than former smokers (1.06; 95% CI, 0.93-1.22). Current heavy smoking (> or = 36 pack-years) was associated with a 45% increased OR for follicular lymphoma (1.45; 95% CI, 1.15-1.82) compared with nonsmokers. CONCLUSIONS: Cigarette smoking may increase the risk of developing follicular lymphoma but does not seem to affect risk of the other non-Hodgkin lymphoma subtypes we examined. Future research is needed to determine the biological mechanism responsible for our subtype-specific results.     

Hepatitis C infection and risk of malignant lymphoma

The association between hepatitis C virus (HCV) infection and risk of malignant lymphoma remains controversial, perhaps due to small-sized studies and low prevalence of HCV in the general population. On the basis of a large Danish-Swedish population-based case-control study, 2,819 lymphoma patients and 1,856 controls of second-generation Danish-Swedish origin were screened for HCV infection using an enzyme-linked immunosorbent assay and a confirming recombinant immunoblot assay (RIBA) test. Positive samples were tested with real-time PCR for the presence of HCV RNA. The association between HCV infection and risk of malignant lymphoma was assessed by logistic regression. When intermediate RIBA test results were interpreted as positive, anti-HCV antibody positivity was associated with a nonsignificant increased risk of non-Hodgkin lymphoma (NHL) overall (odds ratio (OR) = 2.2; 95% confidence interval (CI) 0.9-5.3; n = 20 cases), of B-cell lymphomas combined (OR = 2.4 [1.0-5.8]; n = 20) and of lymphoplasmacytic lymphoma (OR = 5.2 [1.0-26.4]; n = 2). No patients with T-cell or Hodgkin lymphoma were HCV-positive. A more conservative definition of HCV positivity (disregarding intermediate RIBA results) resulted in an OR = 1.6 (0.3-8.5; n = 5) for NHL overall. When the definition was further restricted to require HCV RNA positivity, OR was 1.7 (0.2-16.2; n = 3) for NHL overall. Our findings from a population with a low prevalence of HCV suggest a positive association between HCV and risk of NHL, in particular of B-cell origin.     

Tobacco and alcohol consumption and risk of lymphoma: results of a population-based case-control study in Germany

Changing trends in lifestyle exposures are suggested to be contributing factors to the increasing incidence rates for lymphoma. We investigated the relationship between smoking and alcohol consumption and the risk of lymphoma among adult participants of a population-based case-control study recently conducted in Germany. In 710 case-control pairs, an increased risk of lymphoma was associated with a long duration of smoking (p for trend = 0.01 for men) and smoking of > 20 cigarettes per day(OR = 2.7; 95% CI = 1.4-5.2 for women). Elevated odds ratios were seen for most lymphoma subentities, albeit mostly without reaching statistical significance. A strong association was evident between smoking and multiple myeloma (OR = 2.4, 95% CI = 0.98-5.74 for men; OR = 2.9, 95% CI = 1.1-7.4 for women) and Hodgkin's lymphoma among men (OR = 3.6; 95% CI = 1.7-7.5). Alcohol consumption 10 years prior to the date of interview appeared to decrease the risk of lymphoma. Odds ratios for men who reported alcohol consumption were 53% lower (95% CI = 0.31-0.71) compared to men who drank very little or no alcohol. The same tendency was evident for women, although the association was less pronounced. The inverse relationship was also seen for low amounts of alcohol and did not appear to be restricted to specific types of beverages. Although biologic rationale for a protective effect of alcohol consumption may be given, a more in-depth analysis involving genetic markers is indicated to clarify if ethanol, other components in alcoholic beverages, or factors associated with moderate drinking reduce lymphoma risk among adults. In conclusion, this investigation suggests a positive association between tobacco smoking and lymphoma risk and finds decreased odds ratios among consumers of alcohol.     

A past history of gastric ulcers and Helicobacter pylori infection increase the risk of gastric malignant lymphoma

Helicobacter pylori (H. pylori) is a causative agent for peptic ulcers as well as some types of gastric lymphoma; however, the relationship between a peptic ulcer history in combination with H. pylori infection and the risk of gastric lymphoma has not been fully evaluated. To examine this point, we conducted a case-control study with 645 patients histologically diagnosed as having malignant lymphomas and 3225 non-cancer controls. Plasma H. pylori IgG status was assessed for subgroups for which blood samples were available (116 cases and 114 controls). An association with a history of gastric, but not duodenal ulcers was found for gastric lymphoma [odds ratio (OR) = 5.41, 95% confidence interval (CI): 3.12-9.39]. In the examination according to histological subtype, the OR was high for both gastric mucous-associated lymphoid tissue (MALT) lymphoma (OR = 5.54, 95% CI: 2.56-12.01) and diffuse large B-cell lymphoma (DLBCL) (OR = 7.23, 95% CI: 2.62-19.90). In the analysis of H. pylori antibody, the risk of total gastric lymphoma was associated with H. pylori infection (OR = 5.34, 95% CI: 1.42-20.05). A high prevalence of H. pylori infection was also found for both gastric MALT lymphoma (8 out of 10: 80.0%) and DLBCL (8 out of 9: 88.9%). Further, in subgroup analysis of subjects with H. pylori infection, gastric ulcer history, but not duodenal ulcer history was associated with the risk of gastric lymphoma (OR = 4.15, 95% CI: 1.02-16.89). In conclusion, we found a positive association with a past history of gastric ulcer and H. pylori infection for gastric lymphoma, while duodenal ulcer history was no association. These results suggested the risk of gastric lymphoma increased by interaction between H. pylori infection and gastric ulcer history. Further studies are warranted.     

Cohort studies of association between self-reported allergic conditions,immune-related diagnoses and glioma and meningioma risk

An inverse association between self-reported allergies and glioma and meningioma risk, has been previously observed in case-control studies. Approximately 27% (median) of the information on both glioma and meningioma in these studies, however, is collected from proxy respondents. In fact, the odds ratios (OR) among previous brain tumor studies are inversely related to the proportion of proxy respondents (Pearson correlation coefficient = -0.94; 95% CI = -1.00 to -0.65); this correlation suggests bias. We therefore constructed 3 cohorts based on the Swedish Twin, Hospital Discharge, and Cancer Registries. In Cohorts I (14,535 people developed 37 gliomas and 41 meningiomas) and II (29,573 people developed 42 gliomas and 26 meningiomas) median time from self-report of allergies to brain tumor diagnosis was 15.4 years. Cohort III, which overlaps with Cohorts I and II (52,067 people developed 68 gliomas and 63 meningiomas), was linked to the Swedish Hospital Discharge Registry where pre-brain tumor immune-related discharge diagnoses were recorded. Allergies are inversely associated with glioma risk in Cohort I (Hazard ratio [HR] = 0.45; 95% CI = 0.19-1.07) and among high grade (III and IV, HR = 0.45; 95% CI = 0.11-1.92) but not low grade (I and II, HR = 2.60; 95% CI = 0.86-7.81) gliomas in Cohort II. In Cohort III, immune-related discharge diagnoses are also inversely associated with glioma (HR = 0.46; 95% CI = 0.14-1.49). There is no strong evidence against (and some for) the hypothesis that allergies reduce glioma risk.     

Factors Associated with Delayed Diagnosis of Lymphomas: Experience with Patients from Hematology Centers in Morocco

Background: Moroccan cancer patients usually have to go through several steps before they are diagnosed. It is important to assess factors associated with diagnosis delay for lymphomas, which might have significant effects on survival. The aim of this study was to determine factors leading to late diagnosis of lymphomas. Methods: A cross-sectional study was conducted with three hematology centers in Morocco in 2008, to analyze the impact of sociodemographic and clinical factors on delay-time from symptoms to diagnosis. Results: A total of 151 patients were included in the study. Late delay was significantly associated with gender, (for men compared to women: OR=2.46; 95% CI: 1.06-5.74), to marital status (not married: OR=2.50; 95% CI: 1.06-5.92) and low socioeconomic level (OR=5.82; 95% CI: 2.23-15.17). Late medical delay was significantly associated with having three or more medical visits before diagnosis (Adjusted OR=5.67; 95% CI: 2.55-12.59). Late total delay was observed for patients with three children or less (adjusted OR=4.39; 95% CI: 1.32-14.56), those who were non-married (adjusted OR=2.49; 95% CI: 1.07-5.81), had a non Hodgkin’s lymphoma (Adjusted OR=2.08; 95% CI: 1.06-4.00) or featuring three or more medical visits before the diagnosis (Adjusted OR=2.13; 95% CI: 0.99-5.88). Conclusion: This analysis provides a basis for understanding the sources, extent, and root causes of lymphoma diagnostic delays. The findings appear crucial for system-wide interventions aimed to facilitate clinical management of patients with lymphoma and to improve prognosis and quality of life.     

Non-Hodgkin's lymphoma, obesity and energy homeostasis polymorphisms

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.     

Novel breast cancer risk alleles and endometrial cancer risk

Genome-wide association studies have identified several novel risk alleles for breast cancer. We hypothesized that genetic variants that are associated with breast cancer, a hormone-related disease, would also be associated with endometrial cancer, another hormone-related disease. We conducted a case-control study nested within the Nurses' Health Study and the Women's Health Study to investigate the associations between these 7 newly identified risk alleles for breast cancer and endometrial cancer risk using 692 invasive endometrial cancer cases and 1,723 matched controls. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to assess the risk of endometrial cancer. In contrast to the breast cancer findings, we did not observe an increased risk of endometrial cancer. We observed an inverse association among rs2981582 (FGFR2) variant carriers [OR= 0.75 (95% CI: 0.60-0.95)]. We also observed a nonsignificant inverse association with rs889312 (MAP3K1) variant carriers [OR = 0.85 (95% CI: 0.68-1.05)] and rs1219648 (FGFR2) variant carriers [OR= 0.86 (95% CI: 0.69-1.06) and endometrial cancer risk. We did not observe associations with the other single nucleotide polymorphisms (SNPs) and endometrial cancer risk. Replication studies investigating these polymorphisms and endometrial cancer risk are warranted. However, our findings do suggest the potential importance of biological differences between endometrial and breast cancer with respect to the genes identified in the scans. The molecular mechanisms underlying these differences remain to be defined.     

Role of hepatitis C virus infection in malignant lymphoma in Spain

Hepatitis C virus (HCV) has been implicated in the etiology of malignant lymphomas. We estimated the risk of lymphoma associated with detection of HCV infection. Cases (n = 529) were consecutive patients newly diagnosed with a lymphoid malignancy between 1998 and 2002 in 4 centers in Spain. Lymphomas were diagnosed and classified using the WHO Classification. Controls (n = 600) were hospitalized patients matched to the cases by 5-year age group, gender and study center. Several medical conditions associated with severe immunosuppression precluded the eligibility of controls. Patients underwent a personal interview and blood sampling. HCV positive subjects were considered those with antibody response to third generation ELISA or detection of HCV RNA with Amplicor 2.0. Cases were systematically tested for HIV antibodies. We used the chi(2) test and unconditional logistic regression to estimate the odds ratio (OR) and 95% confidence interval (95% CI) for lymphoma associated with HCV. HCV infection was detected in 40 cases (7.5%) and 23 (3.8%) control subjects. Six of 16 patients with HIV-related lymphomas and 4 of 8 organ-recipient-related lymphomas were HCV positive. The analysis, excluding HIV-infected subjects and organ recipients, led to a prevalence of HCV of 5.9% among cases and 3.8% among controls. The age-, gender- and center-adjusted OR for all lymphomas was 1.58 (95% CI = 0.89-2.79). Among all lymphoma categories, HCV was associated with an increased risk of low grade B-cell lymphomas not otherwise specified (NOS) (OR = 35.98, 95% CI = 4.70-275.4). A 2-fold excess risk associated to HCV was observed for marginal B-cell lymphomas, diffuse large B-cell lymphoma and lymphoma B NOS but the associations were not statistically significant. HCV infection is associated with an increased risk of a broad spectrum of lymphoid neoplasms among non severely immunocompromised subjects in Spain.     

Population-based study of lymphoma in Germany: rationale, study design and first results

A multi-centre, population-based case-control study of lymphoma among adults was conducted in Germany from 1999-2003. The study comprised 700 incident cases (Hodgkin lymphomas and non Hodgkin's lymphoma, NHL) in the age range 18-80 years and 700 age-, sex- and area-matched controls obtained from population registries. Diagnosis was based on the REAL/WHO classification. Information on demographic characteristics, lifestyle, medical history and occupation was obtained by in-person interviews. Each participant was asked for a 24 ml blood sample. First results are focused on basic demographic characteristics, contact to animals, childhood diseases and vaccinations. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. The ORs for lymphoma were decreased for exposure to sheep and goats (OR = 0.7; 95% CI = 0.5-0.9), for rabbits and hare (OR = 0.7; 95% CI = 0.5-0.9), measles infection (OR = 0.6; 95% CI = 0.5-0.9), Bordetella pertussis infection (OR = 0.7; 95% CI = 0.6-0.95), and tetanus vaccination (OR = 0.5; 95% CI = 0.3-0.9). Increased risk of lymphoma was associated with exposure to cattle (OR = 1.3; 95% CI = 1.03-1.7) and immunization for tuberculosis (OR = 1.5; 95% CI = 0.997-2.4). The results of this study are partly consistent with the hygiene hypothesis. The inconsistencies of some of the findings with an explanation by the Th1/Th2 paradigm, however, warrant further research and may indicate that broader explanatory concepts are needed.     

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.     

Allergy-associated symptoms in relation to childhood non-Hodgkin's as contrasted to Hodgkin's lymphomas: a case-control study in Greece and meta-analysis

An increase of the prevalence of childhood allergic diseases and the incidence of childhood Hodgkin's (HL) and non-Hodgkin's lymphoma (NHL) were reported in the late 20th century. Among adults, several studies point to an inverse association with lymphoma; it remains to be confirmed whether allergy is also related to childhood lymphomas and whether the association, if any, is of an aetiologic nature. Between 1996 and 2008, 277 children (aged 0-14 years) with HL (N = 111) or NHL (N = 166) were enrolled in Nationwide Registry for Childhood Hematological Malignancies (NARECHEM), a Greek hospital-based-registry of childhood hematological malignancies. Hospital controls were individually matched to cases on age and sex. Multivariate conditional logistic regression was used to estimate odds ratios (ORs) with 95%confidence intervals (CIs) for associations of allergic diseases and other covariates with childhood HL or NHL risk. Subsequently, we combined our results with those of a French case-control study in a meta-analysis amounting to a total of 330 NHL cases/1478 controls and 239 HL cases/959 controls. After controlling for sociodemographic, perinatal and environmental factors, childhood NHL was less prevalent among children with allergy-associated symptoms overall (OR:0.50, 95%CI:0.27-0.92) or a history of asthma (OR:0.43, 95%CI:0.21-0.88). By contrast, allergy did not seem to be associated with childhood HL risk, although statistical power was limited. Fewer seaside holidays and higher birth weight were also associated with increased childhood NHL risk. The combined OR of the two studies for the association of asthma with NHL risk was: 0.52, 95%CI:0.32-0.84, whereas for HL: 0.86, 95%CI:0.51-1.45. Allergy seems to be strongly and inversely associated with childhood NHL. It remains to be elucidated in future investigations comprising larger populations, focusing on specific disease subtypes and employing more pertinent study-designs, whether this association is genuinely protective.     

C1420T Polymorphism of Cytosolic Serine Hydroxymethyltransferase and Risk of Cancer: a Meta-analysis

A series of studies have explored the role of cytosolic serine hydroxymethyltransferase (SHMT1) C1420Tpolymorphism in cancer risk, but their results were conflicting rather than conclusive. To derive a moreprecise estimation of the association between C1420T and cancer risk, the present meta-analysis of 28 availablestudies with 15,121 cases and 18,023 controls was conducted. The results revealed that there was no significantassociation between the polymorphism and cancer risk overall. In stratified analysis by cancer type (breast cancer,gastrointestinal cancer, leukemia, lymphoma, and others), the results showed that 1420T allele was associatedwith decreased risk in leukemia (CT vs. CC: OR= 0.825, 95% CI =0.704-0.966; and CT+TT vs. CC: OR= 0.838,95% CI = 0.722-0.973), but the same results were not present for other cancer types. When subgroup analysiswas performed by source of control (population-based [PB] and hospital-based [HB]), a borderline inverseassociation was observed for the HB subgroup (CT vs. CC: OR= 0.917, 95% CI = 0.857-0.982) but not for thePB subgroup. Stratifying by geographic area (America, Asia and Europe), significant inverse association wasonly found in Asia subgroup (CT vs. CC: OR= 0.674, 95% CI = 0.522-0.870). In summary, the findings suggestthat SHMT1 C1420T polymorphism is not associated with overall cancer development, but might decreasecancer susceptibility of Asians as well as reduce leukemia risk. Large well-designed epidemiological studies willbe necessary to validate the risk identified in the current meta-analysis.