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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.
- Source :
-
Leukemia [Leukemia] 2022 Jan; Vol. 36 (1), pp. 119-125. Date of Electronic Publication: 2021 Jul 20. - Publication Year :
- 2022
-
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 <superscript>-29</superscript> , 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 <superscript>-63</superscript> , c-statistic = 0.77) and AA-CLL risk (OR = 1.76, P = 5.1 × 10 <superscript>-5</superscript> , 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.<br /> (© 2021. The Author(s).)
- Subjects :
- Adult
Black or African American statistics & numerical data
Aged
Aged, 80 and over
B-Lymphocytes metabolism
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
Lymphocytosis epidemiology
Lymphocytosis genetics
Male
Middle Aged
Prognosis
Risk Factors
United States epidemiology
White People statistics & numerical data
Black or African American genetics
B-Lymphocytes pathology
Biomarkers, Tumor genetics
Leukemia, Lymphocytic, Chronic, B-Cell pathology
Lymphocytosis pathology
White People genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5551
- Volume :
- 36
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Leukemia
- Publication Type :
- Academic Journal
- Accession number :
- 34285341
- Full Text :
- https://doi.org/10.1038/s41375-021-01344-9