Inorganic arsenic methylation capacity and breast cancer by immunohistochemical subtypes in northern Mexican women

Abstract

BackgroundPreviously we reported that inorganic arsenic (iAs) methylation capacity was associated with breast cancer (BC). BC risk factors may vary according to immunohistochemical subtype. Here we explored the relationships between the capacity to methylate iAs and the risk of BC by subtype. MethodsA population-based case-control study was performed in northern Mexico. Patients with available information about BC subtypes (n = 499) were age-matched with healthy controls. Sociodemographic, reproductive, and lifestyle characteristics were obtained. Tumor marker information was obtained from medical records. Cases were classified as HR+ [estrogen receptor (ER+) and/or progesterone (PR+), and human epidermal growth factor receptor 2 (HER2-)], HER2+, or triple negative (TN). Urinary arsenic species were determined by high performance liquid chromatography inductively coupled plasma mass spectrometry (HPLC-ICP-MS), and methylation capacity parameters calculated. Conditional logistic regression models were used to estimate BC risk by subtypes. ResultsUrinary total arsenic varied from 0.60 to 303.29 μg/L. A significant positive association was found between % monomethylarsonic acid (%MMA) and HR + BC: one percent increase resulted in OR%MMA continuous = 2.73, 95% CI: 1.48, 5.05), and this association remained even when %iAs or % dimethylarsinic acid (%DMA) were added to the models with %MMA. MMA/iAs was positively associated with HR + BC (ORMMA/iAs continuous = 2.03, 95% CI: 1.33–3.10). A significant negative association was observed between DMA/MMA and HR + BC (ORDMA/MMA continuous = 0.43, 95% CI: 0.26, 0.71). MMA/iAs was positively associated with TN BC (OR MMA/iAs continuous = 4.05; 95% CI: 1.63, 10.04). ConclusionAltered iAs methylation capacity resulting in higher %MMA was associated with HR+ and TN BC but not with HER2+. MMA is the iAs metabolite more likely to be related to BC. Further research is needed to confirm these results and elucidate the underlying biological mechanisms.