Influence of parent age and gender on anticipation in familial B-cell malignancies

7553 Background: Anticipation (A) occurs when a disease manifests at an earlier age or with increased severity in the next generation. Dependence of A on parent age and sex has not been previously investigated in B-cell malignancies. Methods: 144 pairs [45 mixed Hodgkin’s/non-Hodgkin’s (HD/NHL) and NHL/HD, 44 NHL, 24 HD and 31 CLL] were analyzed retrospectively for presence of anticipation in overall, paternal (PT) and maternal transmission (MT). 90 pairs belong to our familial hematological malignancies database, and 54 were pooled from the literature. A among diseases, as well as PT and MT were compared by t-test. Parent age at conception was correlated with A by Pearson correlation (PC). Results: Age at conception was similar among all malignancies, and overall anticipation varied between −18.93 and −26.61 yr, with no significant difference among diseases, except between CLL and mixed HD/NHL-NHL/HD (−18.93 vs. −26.61 yr, mean difference −7.68 yr, p = 0.03, 95% CI −14.74 to −0.62). A significant PC between the parent age at conception and A was found for all malignancies, with the exception of borderline significance in the case of mixed HD/NHL-NHL/HD MT. No difference in overall A was observed between PT and MT, except for HD (−27.25 vs. −14.25 yr, mean difference −13.00 years, P = 0.02, 95% CI −23.68 to −2.32). However, higher PCs were observed with PT than MT for all diseases (Table). Conclusions: A is present in all familial B-cell malignancies analyzed and it correlates with parent age of conception. Although mean absolute A was more prominent with PT than MT only in the case of HD, all diseases showed a tendency towards a higher PC with PT. Although less prominent than with neurological disease, this phenomenon points towards a germline inheritance of B-cell malignancies and a common genetic basis for HD and NHL. [Table: see text] No significant financial relationships to disclose.