CASE CLUSTERING, EPSTEIN-BARR-VIRUS REED-STERNBERG CELL STATUS AND HERPES-VIRUS SEROLOGY IN HODGKINS-DISEASE - RESULTS OF A CASE-CONTROL STUDY

The Leukaemia Research Fund Data Collection Study (DCS) is a specialis t registry of leukaemias and lymphomas. The present study involves 494 cases of Hodgkin's disease (HD) registered with the DCS between 1985 and 1989. This entire data set has been tested for localised spatial c lustering using an established nearest neighbour method with 18% of al l cases in young people classified as clustered (P < 0.05). No cluster ing was found in older cases. Subsamples were selected from the regist ered cases for a pilot study in which case clustering, herpes virus an tibody titres and Epstein-Barr virus (EBV) presence within the Reed-St ernberg (RS) cells (EBV-RS status) were investigated together. Firstly , a case-control study of HD in young people or nodular sclerosing (NS ) subtype (39 HD cases and 26 healthy controls) found significant elev ation of antibody titres to EBV-viral capsid antigen (VCA), EBV-early antigen (EA) and human herpes virus 6 (HHV-6) in HD cases compared wit h controls, EBV vital genome was present in 5 cases and 4 of these wer e in clusters of HD in young people. Elevation of antibody titres to t he EBV antigens was not associated with case clustering or EBV-RS stat us. Antibody titres to HHV-6 differed significantly between EBV-RS+ an d EBV-RS- cases (P = 0.04). Geometric mean titres for HHV-6 for EBV-RS + and EBV-RS- cases were 11.5 and 73.7, respectively, with the former lower than the control value of 20.5. Secondly, a cluster study includ ed all other cases (n = 14) in clusters containing known EBV-RS+ cases . 3 further cases were EBV-RS+ positive but no cluster consisted entir ely of positive cases. Overall, 5/16 clustered, 2/12 peripheral and 1/ 25 random cases in these studies were EBV-RS+ (P = 0.017). The interpr etation of these results in terms of shared aetiological exposures of cases within clusters and the roles of EBV and HHV-6 is discussed, and hypotheses for testing in future studies proposed.