Kleinstern Geffen, Weinberg J Brice, Parikh Sameer A, Braggio Esteban, Achenbach Sara J, Robinson Dennis P, Norman Aaron D, Rabe Kari G, Boddicker Nicholas J, Vachon Celine M, Lesnick Connie E, Call Timothy G, Brander Danielle M, Rassenti Laura Z, Kipps Thomas J, Olson Janet E, Cerhan James R, Kay Neil E, Furman Richard R, Hanson Curtis A, Shanafelt Tait D, Slager Susan L
School of Public Health, University of Haifa, Haifa, Israel.
Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
Leukemia. 2022 Jan;36(1):119-125. doi: 10.1038/s41375-021-01344-9. Epub 2021 Jul 20.
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.
单克隆B细胞淋巴细胞增多症（MBL）是慢性淋巴细胞白血病（CLL）的前驱疾病。除年龄、性别和CLL家族史外，关于与MBL风险相关的因素知之甚少。已发现41个CLL易感性变异的多基因风险评分（PRS）与欧洲血统（EA）个体的CLL风险相关。在此，我们评估这些变异、PRS和环境因素对MBL风险的影响。我们还评估了非裔美国人（AA）和EA-CLL病例及对照中的这些变异和CLL-PRS。我们的研究纳入了560例EA MBL、869例CLL（696例EA/173例AA）和2866例对照（2631例EA/235例AA）。我们使用逻辑回归，对年龄和性别进行调整，以估计每个种族内的比值比（OR）和95%置信区间。我们发现41个变异中的21个与MBL风险以及CLL-PRS存在显著关联（OR = 1.86，P = 1.9×10，c统计量 = 0.72）。未观察到MBL风险与环境因素之间存在任何关联的明显证据。我们观察到CLL-PRS与EA-CLL风险（OR = 2.53，P = 4.0×10，c统计量 = 0.77）和AA-CLL风险（OR = 1.76，P = 5.1×10，c统计量 = 0.62）存在显著关联。与MBL风险相关的是遗传因素而非环境因素。特别是，CLL-PRS是MBL和EA-CLL风险的有力预测指标，但对AA-CLL的预测作用较小，这表明在该人群中需要进一步开展研究。
