ISGlobal, Barcelona, Spain.
Universitat Pompeu Fabra (UPF), Barcelona, Spain.
J Expo Sci Environ Epidemiol. 2024 Jan;34(1):47-57. doi: 10.1038/s41370-023-00600-7. Epub 2023 Sep 19.
Chronic lymphocytic leukemia (CLL) etiology is poorly understood, and carcinogenic chemicals in drinking and recreational water are candidates.
To evaluate the association between drinking-water exposure to trihalomethanes (THMs) and nitrate as well as lifetime swimming pool attendance and CLL.
During 2010-2013, hospital-based CLL cases and population-based controls were recruited in Spain, providing information on residential histories, type of water consumed and swimming pool attendance. Average THMs and nitrate levels in drinking water were linked to lifetime water consumption. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using mixed models.
Final samples for residential tap water analyses and swimming pool attendance analyses were 144 cases/1230 controls and 157 cases/1240 controls, respectively. Mean (SD) values for average lifetime residential brominated THMs and chloroform in tap water (μg/L), and ingested nitrate (mg/day) were 48.1 (35.6), 18.5 (6.7) and 13.7 (9.6) respectively in controls; and 72.9 (40.7), 17.9 (5.4), and 14.1 (8.8) in CLL cases. For each 10 μg/L increase of brominated THMs and chloroform lifetime-average levels, the ORs (95% CI) were 1.22 (1.14, 1.31) and 0.54 (0.34, 0.87), respectively. For each 5 mg/day increase of ingested nitrate, the OR of CLL was 0.91 (0.80, 1.04). The OR of lifetime pool users (vs. non-users) was 2.38 (1.61, 3.52). Upon performing annual frequency of attending pools analysis through categorization, the second and third categories showed an ORs of 2.36 (1.49, 3.72) and 2.40 (1.51, 3.83), respectively, and P-trend of 0.001.
This study identifies an association of long-term exposure to THMs in drinking water, at concentrations below the regulatory thresholds and WHO guidelines, and swimming pool attendance, with chronic lymphocytic leukemia (CLL). These unprecedented findings are highly relevant since CLL is an incurable cancer with still unknown etiology and because the widespread exposure to chlorination by-products that remain in drinking and recreational water worldwide. Despite the demonstrated carcinogenicity in animals of several chlorination by-products, little is known about their potential risks on human health. This study makes a significant contribution to the search for environmental factors involved in the etiology of CLL and to the evidence of the health impact of these high prevalent water contaminants.
慢性淋巴细胞白血病(CLL)的病因尚不清楚,饮用水和娱乐水中的致癌化学物质是潜在的致病因素。
评估饮用水中三卤甲烷(THMs)和硝酸盐暴露以及终生游泳池使用与 CLL 的相关性。
2010-2013 年期间,在西班牙招募了基于医院的 CLL 病例和基于人群的对照,提供了居住史、饮用水类型和游泳池使用情况的信息。饮用水中 THMs 和硝酸盐的平均水平与终生水摄入量相关联。使用混合模型估计比值比(OR)和 95%置信区间(CI)。
用于住宅自来水分析和游泳池使用分析的最终样本分别为 144 例病例/1230 例对照和 157 例病例/1240 例对照。对照组自来水中平均终生溴代 THMs 和氯仿(μg/L)和摄入硝酸盐(mg/天)值分别为 48.1(35.6)、18.5(6.7)和 13.7(9.6),CLL 病例组分别为 72.9(40.7)、17.9(5.4)和 14.1(8.8)。终生平均水平每增加 10μg/L 的溴代 THMs 和氯仿,OR(95%CI)分别为 1.22(1.14,1.31)和 0.54(0.34,0.87)。摄入硝酸盐每增加 5mg/天,CLL 的 OR 为 0.91(0.80,1.04)。终生游泳池使用者(与非使用者相比)的 OR 为 2.38(1.61,3.52)。通过对游泳池使用频率进行分类,第二和第三类别分别显示 OR 为 2.36(1.49,3.72)和 2.40(1.51,3.83),趋势检验 P 值为 0.001。
本研究发现,饮用水中 THMs 的长期暴露,浓度低于监管阈值和世卫组织指南,以及游泳池使用与慢性淋巴细胞白血病(CLL)之间存在关联。这些前所未有的发现具有重要意义,因为 CLL 是一种无法治愈的癌症,其病因仍未知,而且全球范围内饮用水和娱乐水中仍存在大量的氯化副产物。尽管动物实验证明了几种氯化副产物具有致癌性,但人们对它们对人类健康的潜在风险知之甚少。本研究为寻找 CLL 病因中的环境因素做出了重要贡献,并为这些高流行水污染物对健康的影响提供了证据。