title: Relationship between drugs affecting the renin-angiotensin system and colorectal cancer: The MCC-Spain study.
abstract: The potential protective effect of renin-angiotensin system (RAS) inhibitors is a subject of increasing interest due to their possible role as chemopreventive agents against colorectal cancer (CRC). To evaluate this association, we conducted a case-control study with 2165 cases of colorectal cancer, diagnosed between 2007 and 2012, and 3912 population controls frequency matched (by age, sex and region) from the Spanish multicenter case-control study MCC-Spain. We found a significant protective effect of the angiotensin-converting enzyme Inhibitors (ACEIs) against CRC, limited to the under-65years group (OR=0.65 95%CI (0.48-0.89)) and to a lesser degree to men (OR=0.81 95%CI (0.66-0.99). In contrast, the angiotensin receptor blockers (ARBs) did not show a significant effect. Regarding the duration of use, a greater protection was observed in men as the length of consumption increases. In contrast, in the under-65 stratum, the strongest association was found in short-term treatments. Finally, by analyzing ACEIs effect by colon subsite, we found no differences, except for under 65years old, where the maximum protection was seen in the proximal intestine, descending in the distal and rectum (without statistical significance). In conclusion, our study shows a protective effect on CRC of the ACEis limited to males and people under 65years old, which increases in proximal colon in the latter. If confirmed, these results may suggest a novel approach to proximal CRC prevention, given the shortcomings of colonoscopy screening in this location.
authors.affiliation: Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública- CIBERESP), Madrid, Spain; Division of Epidemiology and Computational Biology, School of Medicine, University of Cantabria, IDIVAL, Santander, Spain. Electronic address: dierssent@unican.es.
authors.forename: Trinidad
authors.initials: T
authors.lastname: Dierssen-Sotos
authors.affiliation: Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública- CIBERESP), Madrid, Spain; Division of Epidemiology and Computational Biology, School of Medicine, University of Cantabria, IDIVAL, Santander, Spain.
authors.forename: Inés
authors.initials: I
authors.lastname: Gómez-Acebo
authors.affiliation: Division of Epidemiology and Computational Biology, School of Medicine, University of Cantabria, IDIVAL, Santander, Spain.
authors.forename: Camilo
authors.initials: C
authors.lastname: Palazuelos
authors.affiliation: Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública- CIBERESP), Madrid, Spain; Department of Gastroenterology and Hepatology, University Hospital of Bellvitge-IDIBELL, Barcelona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Rodriguez-Moranta
authors.affiliation: Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública- CIBERESP), Madrid, Spain; Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain.; Cancer Epidemiology Research Group, Oncology and Hematology Area, IIS Puerta de Hierro (IDIPHIM), Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pérez-Gómez
authors.affiliation: Centro de Salud de Condesa, León, Spain.
authors.forename: José Pedro
authors.initials: JP
authors.lastname: Fernández Vazquez
authors.affiliation: Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública- CIBERESP), Madrid, Spain; Public Health Division of Gipuzkoa, Biodonostia Research Institute, San Sebastian, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Amiano
authors.affiliation: Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública- CIBERESP), Madrid, Spain; Navarra Public Health Institute, Pamplona, Spain; Navarra Institute for Health Research (IdiSNA) Pamplona, Spain.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Barricarte
authors.affiliation: Unidad de Gestión Clínica de Cirugía General y del Aparato Digestivo, Complejo Hospitalario Universitario de Granada, Granada, Spain.
authors.forename: Benito
authors.initials: B
authors.lastname: Mirón-Pozo
authors.affiliation: Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública- CIBERESP), Madrid, Spain; Instituto Universitario de Oncología (IUOPA), Department of Medicine, University of Oviedo, Spain.
authors.forename: Adonina
authors.initials: A
authors.lastname: Tardon
authors.affiliation: Centro de Investigación en Salud y Medio Ambiente (CYSMA), Universidad de Huelva, Huelva, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Capelo
authors.affiliation: Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública- CIBERESP), Madrid, Spain; Dirección General de Salud Pública, FISABIO-Salud Pública, G.Valenciana, Spain.
authors.forename: Rosana
authors.initials: R
authors.lastname: Peiro Pérez
authors.affiliation: Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública- CIBERESP), Madrid, Spain; Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.
authors.forename: José María
authors.initials: JM
authors.lastname: Huerta
authors.affiliation: Department of Gastroenterology, Hospital del Mar, Barcelona, Spain; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Andreu
authors.affiliation: Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública- CIBERESP), Madrid, Spain; Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain.; Cancer Epidemiology Research Group, Oncology and Hematology Area, IIS Puerta de Hierro (IDIPHIM), Madrid, Spain.
authors.forename: Mª Ángeles
authors.initials: MÁ
authors.lastname: Sierra
authors.affiliation: Servicio de Oncología, Complejo Asistencial Universitario de León, León, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Castañón López
authors.affiliation: Department of Pathology, Hospital Universitario Donostia, San Sebastián, Spain.
authors.forename: Irune
authors.initials: I
authors.lastname: Ruiz
authors.affiliation: Navarre Public Health Institute, Pamplona, Spain; Red de Investigación en Servicios Sanitarios en Enfermedades Crónicas (REDISSEC), Pamplona, Spain.
authors.forename: Concepción
authors.initials: C
authors.lastname: Moreno-Iribas
authors.affiliation: Departamento de Medicina Preventiva y Salud Pública, Facultad de Medicina, Universidad de Granada, Granada, Spain; Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Olmedo-Requena
authors.affiliation: Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública- CIBERESP), Madrid, Spain; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain; Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Castaño-Vinyals
authors.affiliation: Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública- CIBERESP), Madrid, Spain; Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain.; Cancer Epidemiology Research Group, Oncology and Hematology Area, IIS Puerta de Hierro (IDIPHIM), Madrid, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Aragonés
authors.affiliation: Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública- CIBERESP), Madrid, Spain; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain; Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
authors.forename: Manolis
authors.initials: M
authors.lastname: Kogevinas
authors.affiliation: Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública- CIBERESP), Madrid, Spain; Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain.; Cancer Epidemiology Research Group, Oncology and Hematology Area, IIS Puerta de Hierro (IDIPHIM), Madrid, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Pollán
authors.affiliation: Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública- CIBERESP), Madrid, Spain; Division of Epidemiology and Computational Biology, School of Medicine, University of Cantabria, IDIVAL, Santander, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Llorca
mesh_terms: D000367:Age Factors; D000368:Aged; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012737:Sex Factors; D013030:Spain / Q000453:epidemiology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors
keywords: Angiotensin converting enzyme inhibitor; Angiotensin receptor blocker; Colorectal cancer