TY - JOUR
T1 - Arsenic methylation capacity is associated with breast cancer in Northern Mexico
AU - López-Carrillo, Lizbeth
AU - Hernández-Ramírez, Raúl Ulises
AU - Gandolfi, A. Jay
AU - Ornelas-Aguirre, José Manuel
AU - Torres-Sánchez, Luisa
AU - Cebrian, Mariano E.
N1 - Funding Information: This study was supported by CONACyT. Fondo Sectorial de Investigación en Salud y Seguridad Social ( 2005-2-14373 , 2009-1-111384 and 2010-1-140962 ). Additional support was provided in part by The Dean Carter Binational Center for Environmental Health Sciences and the NIEHS Superfund Research Program ( ES 04940 ).
PY - 2014/10/1
Y1 - 2014/10/1
N2 - 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.
AB - 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.
KW - Arsenic
KW - Arsenic metabolism
KW - Breast cancer
KW - Case control
KW - Mexico
UR - http://www.scopus.com/inward/record.url?scp=84906222968&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84906222968&partnerID=8YFLogxK
U2 - 10.1016/j.taap.2014.07.013
DO - 10.1016/j.taap.2014.07.013
M3 - Article
C2 - 25062773
SN - 0041-008X
VL - 280
SP - 53
EP - 59
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
IS - 1
ER -