
PMID- 37726507
OWN - NLM
STAT- MEDLINE
DCOM- 20240304
LR  - 20240517
IS  - 1559-064X (Electronic)
IS  - 1559-0631 (Print)
IS  - 1559-0631 (Linking)
VI  - 34
IP  - 1
DP  - 2024 Jan
TI  - Lifetime exposure to brominated trihalomethanes in drinking water and swimming 
      pool attendance are associated with chronic lymphocytic leukemia: a 
      Multicase-Control Study in Spain (MCC-Spain).
PG  - 47-57
LID - 10.1038/s41370-023-00600-7 [doi]
AB  - BACKGROUND: Chronic lymphocytic leukemia (CLL) etiology is poorly understood, and 
      carcinogenic chemicals in drinking and recreational water are candidates. 
      OBJECTIVE: To evaluate the association between drinking-water exposure to 
      trihalomethanes (THMs) and nitrate as well as lifetime swimming pool attendance 
      and CLL. METHODS: 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. 
      RESULTS: 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 (mug/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 mug/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. IMPACT STATEMENT: 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.
CI  - (c) 2023. The Author(s).
FAU - Donat-Vargas, Carolina
AU  - Donat-Vargas C
AD  - ISGlobal, Barcelona, Spain.
AD  - Universitat Pompeu Fabra (UPF), Barcelona, Spain.
AD  - CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.
AD  - Unit of Cardiovascular and Nutritional Epidemiology, Intitute of Environmental 
      Medicine, Karolinska Institutet, Stockholm, Sweden.
FAU - Kogevinas, Manolis
AU  - Kogevinas M
AD  - ISGlobal, Barcelona, Spain.
AD  - Universitat Pompeu Fabra (UPF), Barcelona, Spain.
AD  - CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.
AD  - IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
FAU - Benavente, Yolanda
AU  - Benavente Y
AD  - CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.
AD  - Unit of Molecular and Genetic Epidemiology in Infections and Cancer 
      (UNIC-Molecular), Cancer Epidemiology Research Programme, IDIBELL, Catalan 
      Institute of Oncology, 08908, L'Hospitalet de Llobregat, Spain.
FAU - Costas, Laura
AU  - Costas L
AD  - CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.
AD  - Unit of Molecular and Genetic Epidemiology in Infections and Cancer 
      (UNIC-Molecular), Cancer Epidemiology Research Programme, IDIBELL, Catalan 
      Institute of Oncology, 08908, L'Hospitalet de Llobregat, Spain.
FAU - Campo, Elias
AU  - Campo E
AD  - Haematopathology Section, Hospital Clinic of Barcelona, Institut 
      d'Investigaciones Biomediques August Pi I Sunyer (IDIBAPS), University of 
      Barcelona, Centrode Investigacion Biomedica en Red de Cancer (CIBERONC), 
      Barcelona, Spain.
FAU - Castano-Vinyals, Gemma
AU  - Castano-Vinyals G
AD  - ISGlobal, Barcelona, Spain.
AD  - Universitat Pompeu Fabra (UPF), Barcelona, Spain.
AD  - CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.
AD  - IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
FAU - Fernandez-Tardon, Guillermo
AU  - Fernandez-Tardon G
AD  - CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.
AD  - Health Research Institute of Asturias, ISPA, Oviedo, Spain.
FAU - Llorca, Javier
AU  - Llorca J
AD  - CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.
AD  - Faculty of Medicine, University of Cantabria, Santander, Spain.
FAU - Gomez-Acebo, Ines
AU  - Gomez-Acebo I
AD  - CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.
AD  - Faculty of Medicine, University of Cantabria, Santander, Spain.
AD  - IDIVAL. Instituto de Investigacion Sanitaria Valdecilla, 39011, Santander, Spain.
FAU - Aragones, Nuria
AU  - Aragones N
AD  - CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.
AD  - Epidemiology Section, Public Health Division, Department of Health of Madrid, 
      Madrid, Spain.
FAU - Pollan, Marina
AU  - Pollan M
AD  - CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.
AD  - Cancer and Environmental Epidemiology Unit, National Centre for Epidemiology, 
      Carlos III Institute of Health, Madrid, Spain.
FAU - Casabonne, Delphine
AU  - Casabonne D
AD  - CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.
AD  - Unit of Molecular and Genetic Epidemiology in Infections and Cancer 
      (UNIC-Molecular), Cancer Epidemiology Research Programme, IDIBELL, Catalan 
      Institute of Oncology, 08908, L'Hospitalet de Llobregat, Spain.
FAU - Villanueva, Cristina M
AU  - Villanueva CM
AD  - ISGlobal, Barcelona, Spain. cristina.villanueva@isglobal.org.
AD  - Universitat Pompeu Fabra (UPF), Barcelona, Spain. 
      cristina.villanueva@isglobal.org.
AD  - CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain. 
      cristina.villanueva@isglobal.org.
AD  - IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. 
      cristina.villanueva@isglobal.org.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230919
PL  - United States
TA  - J Expo Sci Environ Epidemiol
JT  - Journal of exposure science & environmental epidemiology
JID - 101262796
RN  - 0 (Drinking Water)
RN  - 0 (Trihalomethanes)
RN  - 7V31YC746X (Chloroform)
RN  - 0 (Nitrates)
SB  - IM
MH  - Animals
MH  - Humans
MH  - *Drinking Water
MH  - *Leukemia, Lymphocytic, Chronic, B-Cell/chemically induced/epidemiology
MH  - Trihalomethanes/adverse effects
MH  - Chloroform
MH  - Nitrates/adverse effects
MH  - Spain/epidemiology
MH  - *Swimming Pools
PMC - PMC10907291
OTO - NOTNLM
OT  - Cancer
OT  - Chronic lymphocytic leukemia
OT  - Nitrate
OT  - Trihalomethanes
OT  - Water contaminants
OT  - swimming pools
COIS- The authors declare no competing interests.
EDAT- 2023/09/20 00:43
MHDA- 2024/03/04 06:43
PMCR- 2023/09/19
CRDT- 2023/09/19 23:33
PHST- 2023/04/04 00:00 [received]
PHST- 2023/08/23 00:00 [accepted]
PHST- 2023/08/22 00:00 [revised]
PHST- 2024/03/04 06:43 [medline]
PHST- 2023/09/20 00:43 [pubmed]
PHST- 2023/09/19 23:33 [entrez]
PHST- 2023/09/19 00:00 [pmc-release]
AID - 10.1038/s41370-023-00600-7 [pii]
AID - 600 [pii]
AID - 10.1038/s41370-023-00600-7 [doi]
PST - ppublish
SO  - J Expo Sci Environ Epidemiol. 2024 Jan;34(1):47-57. doi: 
      10.1038/s41370-023-00600-7. Epub 2023 Sep 19.
