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 Hanson; Tait D Shanafelt; Susan L Slager

doi:10.1038/s41375-021-01344-9

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

Journal article

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Peer reviewed

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, …

Leukemia, Vol.36(1), pp.119-125

01/2022

DOI: 10.1038/s41375-021-01344-9

PMCID: PMC8727288

PMID: 34285341

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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 , 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 , c-statistic = 0.77) and AA-CLL risk (OR = 1.76, P = 5.1 × 10 , 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.

Adult

Aged

Aged, 80 and over

B-Lymphocytes - metabolism

B-Lymphocytes - pathology

Biomarkers, Tumor - genetics

Black or African American - genetics

Black or African American - statistics & numerical data

Case-Control Studies

Clone Cells

Female

Follow-Up Studies

Humans

Immunoglobulins - genetics

Immunoglobulins - immunology

Immunophenotyping

Leukemia, Lymphocytic, Chronic, B-Cell - epidemiology

Leukemia, Lymphocytic, Chronic, B-Cell - genetics

Leukemia, Lymphocytic, Chronic, B-Cell - pathology

Lymphocytosis - epidemiology

Lymphocytosis - genetics

Lymphocytosis - pathology

Male

Middle Aged

Prognosis

Risk Factors

United States - epidemiology

White People - genetics

White People - statistics & numerical data

Details

Title: Subtitle: Polygenic risk score and risk of monoclonal B-cell lymphocytosis in caucasians and risk of chronic lymphocytic leukemia (CLL) in African Americans
Creators: Geffen Kleinstern - Mayo Clinic
J Brice Weinberg - Durham VA Medical Center
Sameer A Parikh - Mayo Clinic
Esteban Braggio - Phoenix (United States)
Sara J Achenbach - Mayo Clinic
Dennis P Robinson - Mayo Clinic
Aaron D Norman - Mayo Clinic
Kari G Rabe - Mayo Clinic
Nicholas J Boddicker - Mayo Clinic
Celine M Vachon - Mayo Clinic
Connie E Lesnick - Mayo Clinic
Timothy G Call - Mayo Clinic
Danielle M Brander - Duke University
Laura Z Rassenti - University of California San Diego
Thomas J Kipps - University of California San Diego
Janet E Olson - Mayo Clinic
James R Cerhan - Mayo Clinic
Neil E Kay - Mayo Clinic
Richard R Furman - Weill Cornell Medicine
Curtis A Hanson - Mayo Clinic
Tait D Shanafelt - Stanford University
Susan L Slager - Division of Hematology, Mayo Clinic, Rochester, MN, USA. slager@mayo.edu.
Resource Type: Journal article
Publication Details: Leukemia, Vol.36(1), pp.119-125
DOI: 10.1038/s41375-021-01344-9
PMID: 34285341
PMCID: PMC8727288
NLM abbreviation: Leukemia
ISSN: 0887-6924
eISSN: 1476-5551
Grant note: R01 CA200703 / NCI NIH HHS R01 AG058266 / NIA NIH HHS P30 CA014236 / NCI NIH HHS R01 CA197120 / NCI NIH HHS R25 CA092049 / NCI NIH HHS P01 CA081534 / NCI NIH HHS P30 CA015083 / NCI NIH HHS R01 CA235026 / NCI NIH HHS P50 CA097274 / NCI NIH HHS
Language: English
Date published: 01/2022
Academic Unit: Epidemiology
Record Identifier: 9984368211302771

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