Hodgkin's lymphoma and infection: findings from a UK case-control study.

Between 1998 and 2003, 214 people with Hodgkin's lymphoma and 214 controls randomly selected from population registers in the north of England (after matching for age and sex) were recruited and their primary care medical records examined for details of clinical diagnoses due to infectious and non-infectious conditions in the preceding 15 years. In the year before diagnosis of Hodgkin's lymphoma, almost all cases (99%) visited their general practitioner (GP) at least once. In comparison with controls, the excess was evident both for visits with an infection (odd's ratio (OR)=2.1; 95% confidence interval (CI) 1.4-3.2) and for visits with non-infectious problems (OR=17.2; 95% CI 6.7-43.9). During the rest of the 15-year period prior to diagnosis, the proportion of people visiting their GP with a non-infectious condition did not differ between cases and controls. In contrast, compared to controls, there was an excess of cases visiting the GP with an infection, a finding that was evident for at least a decade prior to diagnosis and increased linearly with time (P=0.02). This excess was not due to a specific infection(s) and may reflect underlying immune abnormality. Alternatively, infection may cause B-cell proliferation from which a malignant clone may evolve.

Birth order and sibship size: evaluation of the role of selection bias in a case-control study of non-Hodgkin's lymphoma.

Substantial heterogeneity has been observed among case-control studies investigating associations between non-Hodgkin's lymphoma and familial characteristics, such as birth order and sibship size. The potential role of selection bias in explaining such heterogeneity is considered within this study. Selection bias according to familial characteristics and socioeconomic status is investigated within a United Kingdom-based case-control study of non-Hodgkin's lymphoma diagnosed during 1998-2001. Reported distributions of birth order and maternal age are each compared with expected reference distributions derived using national birth statistics from the United Kingdom. A method is detailed in which yearly data are used to derive expected distributions, taking account of variability in birth statistics over time. Census data are used to reweight both the case and control study populations such that they are comparable with the general population with regard to socioeconomic status. The authors found little support for an association between non-Hodgkin's lymphoma and birth order or family size and little evidence for an influence of selection bias. However, the findings suggest that between-study heterogeneity could be explained by selection biases that influence the demographic characteristics of participants.

Non-Hodgkin's lymphoma and family history of hematologic malignancy.

Familial aggregation of non-Hodgkin's lymphoma, and the co-occurrence of non-Hodgkin's lymphoma and other hematologic malignancies within families, provide evidence for genetic or common environmental etiologies for these conditions. The authors analyzed the association between non-Hodgkin's lymphoma risk and family history of hematologic malignancy using a case-control study based in the United Kingdom. The study recruited patients diagnosed with lymphoma during 1998-2001. Results indicated an increased risk of non-Hodgkin's lymphoma for persons with a positive family history of any hematologic malignancy (odds ratio = 1.70, 95% confidence interval: 1.08, 2.69) and particularly of any lymphoma (odds ratio = 2.43, 95% confidence interval: 1.14, 5.19). The authors compared the number of hematologic malignancies among relatives reported by the cases and controls with that expected from the national rates of hematologic malignancy registered in the United Kingdom. Through these comparisons, the authors raise questions about the validity of self-reported family history of hematologic malignancy, especially regarding identification of specific types of hematologic malignancies. Given these reservations, they consider how future epidemiologic studies may contribute to further understanding the role of familial susceptibility in non-Hodgkin's lymphoma.

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.

Occupational exposure to electromagnetic fields and acute leukaemia: analysis of a case-control study.

AIMS: To investigate whether the risk of acute leukaemia among adults is associated with occupational exposure to electromagnetic fields. METHODS: Probable occupational exposure to electromagnetic fields at higher than typical residential levels was investigated among 764 patients diagnosed with acute leukaemia during 1991-96 and 1510 sex and age matched controls. A job exposure matrix was applied to the self reported employment histories to determine whether or not a subject was exposed to electromagnetic fields. Risks were assessed using conditional logistic regression for a matched analysis. RESULTS: Study subjects considered probably ever exposed to electromagnetic fields at work were not at increased risk of acute leukaemia compared to those considered never exposed. Generally, no associations were observed on stratification by sex, leukaemia subtype, number of years since exposure stopped, or occupation; there was no evidence of a dose-response effect using increasing number of years exposed. However, relative to women considered never exposed, a significant excess of acute lymphoblastic leukaemia was observed among women probably exposed to electromagnetic fields at work that remained increased irrespective of time prior to diagnosis or job ever held. CONCLUSION: This large population based case-control study found little evidence to support an association between occupational exposure to electromagnetic fields and acute leukaemia. While an excess of acute lymphoblastic leukaemia among women was observed, it is unlikely that occupational exposure to electromagnetic fields was responsible, given that increased risks remained during periods when exposure above background levels was improbable.

Polymorphism in glutathione S-transferase P1 is associated with susceptibility to chemotherapy-induced leukemia.

Glutathione S-transferases (GSTs) detoxify potentially mutagenic and toxic DNA-reactive electrophiles, including metabolites of several chemotherapeutic agents, some of which are suspected human carcinogens. Functional polymorphisms exist in at least three genes that encode GSTs, including GSTM1, GSTT1, and GSTP1. We hypothesize, therefore, that polymorphisms in genes that encode GSTs alter susceptibility to chemotherapy-induced carcinogenesis, specifically to therapy-related acute myeloid leukemia (t-AML), a devastating complication of long-term cancer survival. Elucidation of genetic determinants may help to identify individuals at increased risk of developing t-AML. To this end, we have examined 89 cases of t-AML, 420 cases of de novo AML, and 1,022 controls for polymorphisms in GSTM1, GSTT1, and GSTP1. Gene deletion of GSTM1 or GSTT1 was not specifically associated with susceptibility to t-AML. Individuals with at least one GSTP1 codon 105 Val allele were significantly over-represented in t-AML cases compared with de novo AML cases [odds ratio (OR), 1.81; 95% confidence interval (CI), 1.11-2.94]. Moreover, relative to de novo AML, the GSTP1 codon 105 Val allele occurred more often among t-AML patients with prior exposure to chemotherapy (OR, 2.66; 95% CI, 1.39-5.09), particularly among those with prior exposure to known GSTP1 substrates (OR, 4.34; 95% CI, 1.43-13.20), and not among those t-AML patients with prior exposure to radiotherapy alone (OR,1.01; 95% CI, 0.50-2.07). These data suggest that inheritance of at least one Val allele at GSTP1 codon 105 confers a significantly increased risk of developing t-AML after cytotoxic chemotherapy, but not after radiotherapy.

Karyotype and age in acute myeloid leukemia. Are they linked?

A novel hierarchical cytogenetic classification for acute myeloid leukemia (AML) has been developed. Patients with successful cytogenetics and a diagnosis of AML were categorized into four mutually exclusive karyotype groups: normal, translocation, deletion and trisomy. Patients with more than one chromosomal abnormality were classified using the hierarchy: established translocation>established deletion>established trisomy>non-established translocation>non-established deletion>non-established trisomy. A total of 593 AML patients from a large population-based case-control study of acute leukemia were classified according to their diagnostic karyotype. The four karyotype groups showed different age distributions. Overall the frequency of patients increased with age as did the frequency of patients with a deletion, trisomy or normal karyotype. Although the increase of patients with age was much sharper for patients with a deletion. In contrast, the distribution of patients with a translocation was roughly constant with age. We concluded that there was a link between karyotype and the age of the patient at diagnosis. Furthermore, two karyotype groups, translocations and deletions, may define disease entities with different etiologies. This novel cytogenetic classification will allow other studies to examine whether AML cases with very different types of chromosomal abnormality have the same etiology.