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Direct evidence for a polygenic etiology in familial multiple myeloma

Britt-Marie Halvarsson1, Anna-Karin Wihlborg1, Mina Ali1

  • 1Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden.

Blood Advances
|January 4, 2018
PubMed

Insights

Common genetic risk factors contribute to familial multiple myeloma (MM). This study found an enrichment of these risk alleles in familial cases, suggesting a polygenic basis for about one-third of these rare blood cancer occurrences.

Area of Science:

  • Genetics
  • Hematology
  • Oncology

Background:

  • Common risk alleles for multiple myeloma (MM) have been identified.
  • The role of these common risk alleles in familial MM remains unknown.

Purpose of the Study:

  • To investigate the contribution of common risk alleles to familial multiple myeloma.
  • To determine the etiological basis of familial hematologic malignancies.

Main Methods:

  • Analysis of 38 familial MM cases linked via Swedish nationwide registries.
  • Comparison of allele frequencies in familial cases versus sporadic cases and population controls.
  • Application of mixture modeling to estimate the proportion of familial cases attributable to genetic enrichments.

Main Results:

  • An enrichment of common MM risk alleles was observed in familial cases compared to sporadic cases and controls.
  • Polygenic risk scores showed significant association with familial MM.
  • Mixture modeling estimated that approximately one-third of familial MM cases are influenced by these genetic enrichments.

Conclusions:

  • This study provides the first direct evidence for a polygenic etiology in familial multiple myeloma.
  • Common genetic variants play a significant role in the development of familial hematologic malignancies.

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