Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.
Champalimaud Foundation, Lisbon, Portugal.
Cancer Epidemiol Biomarkers Prev. 2024 Nov 1;33(11):1423-1432. doi: 10.1158/1055-9965.EPI-24-0620.
Risk factors including smoking, alcohol intake, physical activity (PA), and sleep patterns have been associated with cancer risk. Clonal hematopoiesis (CH), including mosaic chromosomal alterations and clonal hematopoiesis of indeterminate potential, is linked to increased hematopoietic cancer risk and could be used as common preclinical intermediates for the better understanding of associations of risk factors with rare hematologic malignancies.
We analyzed cross-sectional data from 478,513 UK Biobank participants without hematologic malignancies using multivariable-adjusted analyses to assess the associations between lifestyle factors and CH types.
Smoking was reinforced as a potent modifiable risk factor for multiple CH types, with dose-dependent relationships persisting after cessation. Males in socially deprived areas of England had a lower risk of mosaic loss of chromosome Y (mLOY), females with moderate/high alcohol consumption (2-3 drinks/day) had increased mosaic loss of the X chromosome risk [OR = 1.17; 95% confidence interval (CI), 1.09-1.25; P = 8.31 × 10-6] compared with light drinkers, active males (moderate-high PA) had elevated risks of mLOY (PA category 3: OR = 1.06; 95% CI, 1.03-1.08; P = 7.57 × 10-6), and men with high body mass index (≥40) had reduced risk of mLOY (OR = 0.57; 95% CI, 0.51-0.65; P = 3.30 × 10-20). Sensitivity analyses with body mass index adjustment attenuated the effect in the mLOY-PA associations (IPAQ2: OR = 1.03; 95% CI, 1.00-1.06; P = 2.13 × 10-2 and IPAQ3: OR = 1.03; 95% CI, 1.01-1.06; P = 7.77 × 10-3).
Our study reveals associations between social deprivation, smoking, and alcohol consumption and CH risk, suggesting that these exposures could contribute to common types of CH and potentially rare hematologic cancers.
This study underscores the impact of lifestyle factors on CH frequency, emphasizing social, behavioral, and clinical influences and the importance of sociobehavioral contexts when investigating CH risk factors.
吸烟、饮酒、体力活动（PA）和睡眠模式等风险因素与癌症风险相关。克隆性造血（CH），包括镶嵌染色体改变和不确定潜能的克隆性造血，与造血系统癌症风险增加有关，可作为更好地理解风险因素与罕见血液恶性肿瘤关联的常见临床前中间产物。
我们使用多变量调整分析，分析了来自 478513 名无血液恶性肿瘤的英国生物库参与者的横断面数据，以评估生活方式因素与 CH 类型之间的关联。
吸烟被强化为多种 CH 类型的潜在可改变风险因素，且在停止吸烟后仍存在剂量依赖性关系。英格兰社会贫困地区的男性患镶嵌性 Y 染色体丢失（mLOY）的风险较低，而中度/大量饮酒（每天 2-3 杯）的女性患镶嵌性 X 染色体丢失的风险增加[比值比（OR）=1.17；95%置信区间（CI），1.09-1.25；P=8.31×10-6]，与轻度饮酒者相比，活跃的男性（中/高强度 PA）的 mLOY 风险升高（PA 类别 3：OR=1.06；95%CI，1.03-1.08；P=7.57×10-6），而高体重指数（≥40）的男性 mLOY 风险降低（OR=0.57；95%CI，0.51-0.65；P=3.30×10-20）。敏感性分析表明，PA 与 mLOY 之间的关联在调整体重指数后减弱（IPAQ2：OR=1.03；95%CI，1.00-1.06；P=2.13×10-2；IPAQ3：OR=1.03；95%CI，1.01-1.06；P=7.77×10-3）。
我们的研究揭示了社会贫困、吸烟和饮酒与 CH 风险之间的关联，提示这些暴露可能导致常见类型的 CH 和潜在的罕见血液恶性肿瘤。
本研究强调了生活方式因素对 CH 频率的影响，强调了社会、行为和临床影响，以及在研究 CH 风险因素时社会行为背景的重要性。
