Arsenic methylation capacity is associated with breast cancer in northern Mexico

作者：Lopez Carrillo Lizbeth; Ulises Hernandez Ramirez Raid; Gandolfi A Jay; Manuel Ornelas Aguirre Jose; Torres Sanchez Luisa; Cebrian Mariano E^*

来源：Toxicology and Applied Pharmacology, 2014, 280(1): 53-59.

DOI：10.1016/j.taap.2014.07.013

• Arsenic
• Arsenic metabolism
• Breast cancer
• Case control
• Mexico

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 303.29 mu g/L. Most women (86%) had TAs-AsB levels below As biological exposure index (35 mu g/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.

• 出版日期2014-10-1