Discovery of novel etiological factors for B-cell malignancies is hindered by the heterogeneity of these diseases. The identification of important multi-cancer profiles provides a new avenue for discovery, but requires novel approaches and specific resources. The Utah Population Database (UPDB) includes extensive genealogy for 5 million Utahns (from three to 18 generations). The UPDB also includes over 360,000 cancer diagnoses from the NCI SEER Utah Cancer Registry, making it a unique and ideal resource for analyzing cancer patterns in families. Here we performed a multi-cancer clustering approach to identify patterns of familial clustering of cancers in high-risk CLL families. Other cancers considered in the cancer profiles were: Hodgkins lymphoma, follicular lymphoma, diffuse large B-cell lymphoma, multiple myeloma and 25 solid tumors. High risk CLL pedigrees were extracted from the UPDB. Based on cancer rates in UPDB, standardized incidence ratios were calculated for each pedigree for each of the 29 cancers. These vectors of cancer risks per pedigree were used as the basis for k-mediods clustering of the high-risk CLL families. Resulting clusters of families share similar co-aggregations of other B-cell malignancies and solid tumors. High-risk CLL families with similar multi-cancer profiles may be more etiologically homogeneous and provide improved power for the identification of underlying risk factors.

Citation Format: Nathan Scott Harris. Multi-cancer profiles in high-risk CLL families [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 802.