Polygenic risk score and risk of monoclonal B-cell lymphocytosis in caucasians and risk of chronic lymphocytic leukemia (CLL) in African Americans

Geffen Kleinstern, J. Brice Weinberg, Sameer A. Parikh, Esteban Braggio, Sara J. Achenbach, Dennis P. Robinson, Aaron D. Norman, Kari G. Rabe, Nicholas J. Boddicker, Celine M. Vachon, Connie E. Lesnick, Timothy G. Call, Danielle M. Brander, Laura Z. Rassenti, Thomas J. Kipps, Janet E. Olson, James R. Cerhan, Neil E. Kay, Richard R. Furman, Curtis A. HansonTait D. Shanafelt, Susan L. Slager

Research output: Contribution to journalArticlepeer-review

Abstract

Monoclonal B-cell lymphocytosis (MBL) is a precursor to CLL. Other than age, sex, and CLL family-history, little is known about factors associated with MBL risk. A polygenic-risk-score (PRS) of 41 CLL-susceptibility variants has been found to be associated with CLL risk among individuals of European-ancestry(EA). Here, we evaluate these variants, the PRS, and environmental factors for MBL risk. We also evaluate these variants and the CLL-PRS among African-American (AA) and EA-CLL cases and controls. Our study included 560 EA MBLs, 869 CLLs (696 EA/173 AA), and 2866 controls (2631 EA/235 AA). We used logistic regression, adjusting for age and sex, to estimate odds ratios (OR) and 95% confidence intervals within each race. We found significant associations with MBL risk among 21 of 41 variants and with the CLL-PRS (OR = 1.86, P = 1.9 × 10−29, c-statistic = 0.72). Little evidence of any association between MBL risk and environmental factors was observed. We observed significant associations of the CLL-PRS with EA-CLL risk (OR = 2.53, P = 4.0 × 10−63, c-statistic = 0.77) and AA-CLL risk (OR = 1.76, P = 5.1 × 10−5, c-statistic = 0.62). Inherited genetic factors and not environmental are associated with MBL risk. In particular, the CLL-PRS is a strong predictor for both risk of MBL and EA-CLL, but less so for AA-CLL supporting the need for further work in this population.

Original languageEnglish
Pages (from-to)119-125
Number of pages7
JournalLeukemia
Volume36
Issue number1
DOIs
StatePublished - Jan 2022

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health grants, R25 CA92049 (Mayo Cancer Genetic Epidemiology Training Program), R01 AG58266, R01 CA235026, R01 CA197120, R01 CA200703, P50 CA097274, P01-CA081534, and the VA Research Service. The Mayo Clinic Center for Individualized Medicine – provided the Mayo Clinic Biobank materials.

Publisher Copyright:
© 2021, The Author(s).

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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