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Analysis of 153,115 patients with hematological malignancies refines the spectrum of familial risk

Amit Sud, Subhayan Chattopadhyay, Hauke Thomsen, Kristina Sundquist, Jan Sundquist, Richard S. Houlston and Kari Hemminki

Key Points

  • Substantive familial risks are associated with each hematological malignancy, younger diagnosis age and multiple affected relatives.

  • The familial relative risks provide evidence for shared etiology between the specific hematological malignancies.

Abstract

Estimating familial cancer risks is clinically important in being able to discriminate between individuals in the population at differing risk of malignancy. To gain insight into the familial risk of the different hematological malignancies and their possible inter-relationship, we analyzed data on over 16 million individuals from the Swedish Family-Cancer Database. After identifying 153,115 patients diagnosed with a primary hematological malignancy, we quantified familial relative risks (FRRs) by calculating standardized incident ratios (SIR) in their 391,131 first-degree relatives. The majority of hematological malignancies showed increased FRRs for the same tumor type, with the highest FRRs being observed for mixed cellularity Hodgkin lymphoma (SIR=16.7), lymphoplasmacytic lymphoma (SIR=15.8) and mantle cell lymphoma (SIR=13.3). There was evidence for pleiotropic relationships, notably chronic lymphocytic leukemia (CLL) was associated with an elevated familial risk of other B-cell tumors and myeloproliferative neoplasms. Collectively these data provide evidence for shared etiological factors for many hematological malignancies and provide information for identifying individuals at increased risk as well as informing future gene discovery initiatives.

  • Submitted January 18, 2019.
  • Revision received August 5, 2019.
  • Accepted June 26, 2019.