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Int J Cancer. 2016 Jul 15;139(2):334-46. doi: 10.1002/ijc.30083. Epub 2016 Apr 4.

Colorectal cancer risk and nitrate exposure through drinking water and diet.

Author information

1
ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
2
Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
3
CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
4
Cancer and Environmental Epidemiology Unit, National Centre for Epidemiology, Carlos III Institute of Health, Madrid, Spain.
5
Cancer Epidemiology Research Group, Oncology and Hematology Area, IIS Puerta De Hierro, Madrid, Spain.
6
Research Group on Gene-Environment Interactions and Health, , University of León, León, Spain.
7
Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
8
Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
9
Unit of Epidemiology and Biostatistics, IRCCS, CRO Aviano National Cancer Institute, Aviano, Italy.
10
University of Cantabria, IDIVAL, Santander, Spain.
11
Public Health Division of Gipuzkoa, San Sebastián, Spain.
12
Biodonostia Research Institute, San Sebastián, Spain.
13
Navarra Public Health Institute, Pamplona, Spain.
14
SOC Igiene ed Epidemiologia Clinica, Azienda Ospedaliera Universitaria, Udine, Italy.
15
Oncology Institute IUOPA, Universidad de Oviedo, Asturias, Spain.
16
Centre for Research in Public Health, Valencia, Spain.
17
Department of Epidemiology IMIB-Arrixaca, Murcia Regional Health Council, Murcia, Spain.
18
Department of Health and Social Sciences, University of Murcia, Murcia, Spain.
19
IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
20
Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
21
University of Barcelona, Barcelona, Spain.
22
University of Modena and Reggio Emilia, Modena, Italy.

Abstract

Ingested nitrate leads to the endogenous synthesis of N-nitroso compounds (NOCs), animal carcinogens with limited human evidence. We aimed to evaluate the risk of colorectal cancer (CRC) associated with nitrate exposure in drinking water and diet. A case-control study in Spain and Italy during 2008-2013 was conducted. Hospital-based incident cases and population-based (Spain) or hospital-based (Italy) controls were interviewed on residential history, water consumption since age 18, and dietary information. Long-term waterborne ingested nitrate was derived from routine monitoring records, linked to subjects' residential histories and water consumption habits. Dietary nitrate intake was estimated from food frequency questionnaires and published food composition databases. Odd ratios (OR) were calculated using mixed models with area as random effect, adjusted for CRC risk factors and other covariables. Generalized additive models (GAMs) were used to analyze exposure-response relationships. Interaction with endogenous nitrosation factors and other covariables was also evaluated. In total 1,869 cases and 3,530 controls were analyzed. Average waterborne ingested nitrate ranged from 3.4 to 19.7 mg/day, among areas. OR (95% CIs) of CRC was 1.49 (1.24, 1.78) for >10 versus ≤5 mg/day, overall. Associations were larger among men versus women, and among subjects with high red meat intake. GAMs showed increasing exposure-response relationship among men. Animal-derived dietary nitrate was associated with rectal, but not with colon cancer risk. In conclusion, a positive association between CRC risk and waterborne ingested nitrate is suggested, mainly among subgroups with other risk factors. Heterogeneous effects of nitrate from different sources (water, animal and vegetables) warrant further research.

KEYWORDS:

case-control studies; colorectal cancer; diet; drinking water; nitrate

PMID:
26954527
DOI:
10.1002/ijc.30083
[Indexed for MEDLINE]
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