Age of onset evidence for anticipation in familial non-Hodgkin's lymphoma

Anticipation, a phenomenon in which an inherited disease is diagnosed at an earlier age in each successive generation of a family, has been demonstrated in certain neurological and haematological disorders. This study was conducted to determine whether anticipation occurs in familial non- Hodgkin's lymphoma (NHL). Eleven published reports of multigenerational familial NHL were analysed for evidence of anticipation, together with 18 previously unreported families with familial NHL. Differences in disease-free survival between generations were determined. The difference between age at onset for each affected parent-child pair was tested against the null hypothesis that there was no difference in age at onset. These analyses were also performed separately using only parent-child pairs with age of onset >25 years to avoid ascertainment bias. In addition, the age at onset distribution of the studied cases was compared with that of the Surveillance Epidemiology and End Results (SEER) Program using data for 1973-98. The median ages at onset in the child and parent generations of all families (48.5 and 71.3 years respectively) and in the selected pairs (52.5 and 71.5 years respectively) were significantly different (P<0.000002 and P<0.000001 respectively). The null hypothesis was rejected for all (P<0.000001) as well as selected pairs (P<0.000003). A significant difference was observed between the ages of onset of the child generation and the SEER population (P<0.009), but not between the parent generation and the SEER population. Anticipation occurs in familial NHL, which suggests a genetic basis for it.