title: Arsenic methylation capacity is associated with breast cancer in northern Mexico.
abstract: Exposure to environmental contaminants, dietary factors and lifestyles may explain worldwide different breast cancer (BC) incidence. Inorganic arsenic (iAs) in the drinking water is a concern in many regions, such as northern Mexico. Studies in several countries have associated the proportion of urinary monomethylarsenic (%MMA) with increased risks for many As-related diseases, including cancer. To investigate the potential relationships between the risk of BC and the capacity to methylate iAs, a hospital-based case-control study (1016 cases/1028 controls) was performed in northern Mexico. Women were directly interviewed about their reproductive histories. The profile of As metabolites in urine was determined by HPLC-ICP-MS and methylation capacity was assessed by metabolite percentages and indexes. Total urinary As, excluding arsenobetaine (TAs-AsB), ranged from 0.26 to 303.29μg/L. Most women (86%) had TAs-AsB levels below As biological exposure index (35μg/L). Women with higher %MMA and/or primary methylation index (PMI) had an increased BC risk (%MMA ORQ5vs.Q1=2.63; 95%CI 1.89,3.66; p for trend <0.001; PMI ORQ5vs.Q1=1.90; 95%CI 1.39,2.59, p for trend <0.001). In contrast, women with higher proportion of urinary dimethylarsenic (%DMA) and/or secondary methylation index (SMI) had a reduced BC risk (%DMA ORQ5vs.Q1=0.63; 95%CI 0.45,0.87, p for trend 0.006; SMI ORQ5vsQ1=0.42, 95%CI 0.31,0.59, p for trend <0.001). Neither %iAs nor total methylation index was associated to BC risk. Inter-individual variations in iAs metabolism may play a role in BC carcinogenesis. Women with higher capacity to methylate iAs to MMA and/or a lower capacity to further methylate MMA to DMA were at higher BC risk.
authors: Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México.
authors: Lizbeth
authors: L
authors: López-Carrillo
authors: Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México.
authors: Raúl Ulises
authors: RU
authors: Hernández-Ramírez
authors: Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ, USA.
authors: A Jay
authors: AJ
authors: Gandolfi
authors: Unidad de Investigación en Epidemiología Clínica del Hospital de Especialidades No. 2, Unidad Médica de Alta Especialidad, Instituto Mexicano del Seguro Social, Ciudad Obregón, Sonora, México.
authors: José Manuel
authors: JM
authors: Ornelas-Aguirre
authors: Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México.
authors: Luisa
authors: L
authors: Torres-Sánchez
authors: Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del IPN, México City, México. Electronic address: mcebrian@cinvestav.mx.
authors: Mariano E
authors: ME
authors: Cebrian
mesh_terms: D001151:Arsenic / Q000652:urine*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000652:urine*; D016022:Case-Control Studies; D060766:Drinking Water / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008745:Methylation; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D014874:Water Pollutants, Chemical / Q000009:adverse effects / Q000652:urine*
chemical_list: D060766:Drinking Water; D014874:Water Pollutants, Chemical; D001151:Arsenic
keywords: Arsenic; Arsenic metabolism; Breast cancer; Case control; Mexico