Anticipation in families with Hodgkin's and non-Hodgkin's lymphoma in their pedigree

Abstract

Anticipation is an earlier onset and/or increasing severity in successive generations. This study was conducted to determine whether anticipation occurs in families that exhibit both Hodgkin's (HD) and non-Hodgkin's (NHL) lymphoma in their pedigrees. Nine published reports of multi-generational lymphoma and 33 previously unreported families with both lymphomas were analysed for evidence of anticipation. The difference between age at onset for each affected related pair was tested against the null hypothesis that there is no difference in age at onset. Differences between disease-free survival in affected generations were determined. These analyses were also conducted separately using only parent – child pairs with an age of onset above 25 years in an effort to avoid ascertainment bias. Age at onset in studied cases was also compared with the HD and NHL series from the Surveillance Epidemiology and End Results (SEER) Program of the US National Cancer Institute. The mean age at onset in the child and parent generations of all case families (60.2 and 35.7 years, respectively) and in the selected pairs (61.5 and 45.6, years) were significantly different (mean difference −24.5 years; P < 0.00001, and −15.9 years, P < 0.00001, respectively). Mean anticipation for parents with HD and children with NHL was −6.8 years (P = 0.01) for the unpublished and −14.4 years (P = 0.002) for the published families (overall anticipation −10.1 years). Mean anticipation for parents with NHL and children with HD was −34.4 years (P < 0.0001) for the unpublished and −32.7 years (P < 0.0001) for the published families (overall anticipation −34.2 years, P < 0.0001). The signed rank test rejected the null hypothesis which stated that there was no difference in age at onset between parents and children for overall, as well as selected pairs (P < 0.00001). The null hypothesis was also rejected for both the parents with HD/children with NHL group and the parents with NHL/children with HD group pairs (P < 0.0001). Age at onset distributions were significantly different for all generations with HD or NHL when compared to the SEER population (P < 0.00001), except for the parents with NHL, which showed no difference. In addition, this study reports four previously unpublished families with three generations of lymphoma in their pedigrees. These data suggest that anticipation occurs in families that exhibit both HL and NHL and that both neoplasms may have a common genetic basis.