Hodgkin lymphoma and Epstein-Barr virus (EBV): no evidence to support hit-and-run mechanism in cases classified as non-EBV-associated.

The Epstein-Barr virus (EBV) is associated with a proportion of Hodgkin lymphoma (HL) cases, and this association is believed to be causal. The aetiology of cases lacking EBV in the tumour cells (EBV HRS-ve), which make up the majority of cases in western countries, is obscure. It has been suggested that EBV may also cause these tumours by using a hit-and-run mechanism. Support for this idea comes from the finding that most young adult patients, who are likely to have a good immune response to EBV, have EBV HRS-ve HL. We investigated this possibility using a combined serologic and molecular approach. Analysis of EBV seroprevalence rates in an epidemiologic study of young adult HL revealed that cases with EBV HRS-ve HL were more likely to be EBV-seronegative than controls. Furthermore, additional studies clearly showed that some HL patients have never been infected by EBV. Quantitative PCR was used to look for the presence of deleted EBV genomes in a series of adult cases with both EBV HRS+ve and HRS-ve HL. Subgenomic fragments were detected in equimolar proportions. This study, therefore, found no evidence to support the idea that a hit-and-run mechanism involving EBV plays a role in the pathogenesis of HL.

Sex ratios and the risks of haematological malignancies.

Although the sex of an individual confers one of the greatest of the known risks for contracting leukaemia and lymphomas, very little attention is paid to these risks. It is the purpose of this paper to stimulate further research in this area. The sex rate ratios are presented for the commoner haematological malignancies. The male excess in the lymphoid cancers is most marked in the youngest age group in non-Hodgkin's lymphoma and Hodgkin's disease, while acute lymphoblastic leukaemia shows equal sex ratios in the childhood peak. Both chronic lymphocytic leukaemia and lymphocytic lymphoma display an unusual pattern, hitherto undescribed, with a large male excess specific to the 40s and 60s age groups. The myeloid sex ratios are all characterized by slight female excess in early adulthood followed by marked male excess. The reasons for these patterns are discussed.

Increasing incidence and descriptive epidemiology of extranodal non-Hodgkin lymphoma in parts of England and Wales.

INTRODUCTION: The incidence of non-Hodgkin lymphoma (NHL) arising from extranodal tissue has been reported to be increasing in Western countries and yet the epidemiology of this heterogeneous disease has been poorly described. PATIENTS AND METHODS: : Cases of extranodal NHL were reported to a specialist population-based registry covering neoplastic hematological conditions in parts of England and Wales from 1986 to 1993. RESULTS: Nearly one third of all NHL, 3556 cases, were extranodal in origin giving a world standardised incidence rate of 1.9/10(5) per year. The most common sites were the skin, stomach and small intestine and high-grade malignancies were predominant. An excess in male incidence was observed for extranodal NHL overall, at all ages, and for most sites. Time-trend analyses indicated significant increases in incidence for all extranodal NHL and NHL of the gastrointestinal tract, skin, central nervous system and male genital organs. Incidence rates increased proportionally more for middle-aged persons, especially females, and for skin lymphomas excluding mycosis fungoides and Sezary disease. CONCLUSION: These results suggest that the rise in incidence of extranodal NHL may be due, at least in part, to an increase specifically in B-cell skin lymphomas and that particular environmental factors such as sunlight might be involved rather than the increases being the results of improvements in diagnostic practices.

Genetic polymorphisms in microsomal epoxide hydrolase and susceptibility to adult acute myeloid leukaemia with defined cytogenetic abnormalities.

Acute myeloid leukaemia (AML) cases with different chromosomal abnormalities may reflect different aetiologies. Benzene exposure, from a number of sources including smoking, is one risk factor for AML. Individual susceptibility to benzene may depend on differences in expression of metabolizing enzymes. We tested the hypothesis that smoking as well as genetic polymorphisms in the microsomal epoxide hydrolase gene (HYL1), an enzyme involved in benzene metabolism, could be risk factors for AML with defined chromosomal abnormalities. Twenty-six AML cases with -7/del(7q) and 24 cases with t(8;21), as well as 43 cases with normal karyotype and 155 age-, sex- and residence-matched controls, were drawn from a large case-control study on adult acute leukaemia. Current smoking was significantly associated with the cytogenetic abnormalities t(8;21) or -7/del(7q) (OR = 4.9; 95%CI = 2.1-11.5) but not with a normal karyotype, relative to individuals who were not current smokers. A putative high activity HYL1 phenotype [exon 3, residue 113 (Tyr/Tyr) and exon 4, residue 139 (His/Arg or Arg/Arg)] was associated with a significantly increased AML risk in men with -7/del(7q) or t(8;21) (OR = 4.4; 95%CI 1.1-17.0) but not with a normal karyotype. This suggests that AML cases with defined chromosomal abnormalities could be related to specific carcinogen exposures and, furthermore, suggests that smoking and genetic polymorphisms in HYL1 could be risk factors for AML with -7/del(7q) or t(8;21).