title: Colorectal cancer risk and nitrate exposure through drinking water and diet.
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.
authors.affiliation: ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.|CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
authors.forename: Nadia
authors.initials: N
authors.lastname: Espejo-Herrera
authors.affiliation: ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.|CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Gràcia-Lavedan
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|Cancer and Environmental Epidemiology Unit, National Centre for Epidemiology, Carlos III Institute of Health, Madrid, Spain.|Cancer Epidemiology Research Group, Oncology and Hematology Area, IIS Puerta De Hierro, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Boldo
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|Cancer and Environmental Epidemiology Unit, National Centre for Epidemiology, Carlos III Institute of Health, Madrid, Spain.|Cancer Epidemiology Research Group, Oncology and Hematology Area, IIS Puerta De Hierro, Madrid, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Aragonés
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|Cancer and Environmental Epidemiology Unit, National Centre for Epidemiology, Carlos III Institute of Health, Madrid, Spain.|Cancer Epidemiology Research Group, Oncology and Hematology Area, IIS Puerta De Hierro, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pérez-Gómez
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|Cancer and Environmental Epidemiology Unit, National Centre for Epidemiology, Carlos III Institute of Health, Madrid, Spain.|Cancer Epidemiology Research Group, Oncology and Hematology Area, IIS Puerta De Hierro, Madrid, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Pollán
authors.affiliation: Research Group on Gene-Environment Interactions and Health, , University of León, León, Spain.
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Molina
authors.affiliation: Research Group on Gene-Environment Interactions and Health, , University of León, León, Spain.
authors.forename: Tania
authors.initials: T
authors.lastname: Fernández
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|Research Group on Gene-Environment Interactions and Health, , University of León, León, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Martín
authors.affiliation: Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: La Vecchia
authors.affiliation: Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bosetti
authors.affiliation: Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tavani
authors.affiliation: Unit of Epidemiology and Biostatistics, IRCCS, CRO Aviano National Cancer Institute, Aviano, Italy.
authors.forename: Jerry
authors.initials: J
authors.lastname: Polesel
authors.affiliation: Unit of Epidemiology and Biostatistics, IRCCS, CRO Aviano National Cancer Institute, Aviano, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Serraino
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|University of Cantabria, IDIVAL, Santander, Spain.
authors.forename: Inés
authors.initials: I
authors.lastname: Gómez Acebo
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|Public Health Division of Gipuzkoa, San Sebastián, Spain.|Biodonostia Research Institute, San Sebastián, Spain.
authors.forename: Jone M
authors.initials: JM
authors.lastname: Altzibar
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|Navarra Public Health Institute, Pamplona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Ardanaz
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|Navarra Public Health Institute, Pamplona, Spain.
authors.forename: Rosana
authors.initials: R
authors.lastname: Burgui
authors.affiliation: SOC Igiene ed Epidemiologia Clinica, Azienda Ospedaliera Universitaria, Udine, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Pisa
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|Oncology Institute IUOPA, Universidad de Oviedo, Asturias, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Fernández-Tardón
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|Oncology Institute IUOPA, Universidad de Oviedo, Asturias, Spain.
authors.forename: Adonina
authors.initials: A
authors.lastname: Tardón
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|Centre for Research in Public Health, Valencia, Spain.
authors.forename: Rosana
authors.initials: R
authors.lastname: Peiró
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|Department of Epidemiology IMIB-Arrixaca, Murcia Regional Health Council, Murcia, Spain.|Department of Health and Social Sciences, University of Murcia, Murcia, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro
authors.affiliation: ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.|CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Castaño-Vinyals
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.|University of Barcelona, Barcelona, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Moreno
authors.affiliation: University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Righi
authors.affiliation: University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Aggazzotti
authors.affiliation: ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.|CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Basagaña
authors.affiliation: ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.|CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Mark
authors.initials: M
authors.lastname: Nieuwenhuijsen
authors.affiliation: ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.|CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Manolis
authors.initials: M
authors.lastname: Kogevinas
authors.affiliation: ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.|CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Villanueva
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000209:etiology*; D004032:Diet / Q000009:adverse effects; D060766:Drinking Water / Q000009:adverse effects; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000009:adverse effects*; D011159:Population Surveillance; D012306:Risk; D013030:Spain / Q000453:epidemiology; D055815:Young Adult
chemical_list: D060766:Drinking Water; D009566:Nitrates
keywords: case-control studies; colorectal cancer; diet; drinking water; nitrate