Non-random Occurrence of Lymphoid Cancers in 141 Lymphoid Cancer Families

S Jones1,2,*, J Voong3,*, R Thomas1, A English1, J Schuetz1, GW Slack4, J Graham3, JM Connors4 and A Brooks-Wilson1,5

1. Canada’s Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC; 2. Department of Medical Genetics, University of British Columbia, Vancouver, BC; 3. Department of Statistics and Actuarial Science, Simon Fraser University, Vancouver, BC; 4. Centre for Lymphoid Cancers, BC Cancer Agency, Vancouver, BC; 5. Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Vancouver, BC

Lymphoid cancers are collectively the fifth most common cancer in Canada and impose a large health and financial burden on individuals and health care systems. Lymphoid cancers are a biologically diverse group of neoplasms, yet familial aggregation of various lymphoproliferative disorders has been observed, suggesting shared genetic risk factors. Specifically, non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) aggregation may be specific to gender, age, ethnicity, infectious agents and familial relationship. Our collection of 141 families with 2 or more members with lymphoid cancer has identified new patterns of lymphoid cancer co-occurrences that vary from the expected population frequencies (P < 0.0001). The pattern differs in families with more affected members (2 cases, P <0.0001; 3 cases, P < 0.0001; 4 or more cases, P < 0.0001). These non-random patterns of co-occurrence show that lymphoid cancer families are not all collections of sporadic cases that arose in the same family by chance. We have also observed earlier age of onset in later generations, a phenomenon referred to as anticipation. Apparent anticipation was seen in NHL (P < 0.0001), HD (P < 0.0001), CLL (P < 0.0013) and all lymphoid cancers together (P < 0.0001). These observations provide evidence for the existence of inherited genetic factors that significantly increase the risk of developing several types of lymphoid cancers, and justifies the use of current genomic methods to identify familial lymphoid cancer susceptibility genes.