TY - JOUR
T1 - Inorganic arsenic methylation capacity and breast cancer by immunohistochemical subtypes in northern Mexican women
AU - López-Carrillo, Lizbeth
AU - Gamboa-Loira, Brenda
AU - Gandolfi, A. Jay
AU - Cebrián, Mariano E.
N1 - Funding Information: We are deeply grateful to the women and hospitals which participated in the study and to: Reina Collado for administrative support, Rosa Maria Garcia Hernández and Michael Kopplin for technical assistance in the process of measuring urinary creatinine and arsenic concentrations. This study was supported by CONACyT , Fondo Sectorial de Investigación en Salud y Seguridad Social [ 2005-2-14373 , 2009-1-111384 , 2010-1-140962 and 2016–272632 ]. Additional support was provided in part by The Dean Carter Binational Center for Environmental Health Sciences ( University of Arizona ) and the NIEHS Superfund Research Program [ ES 04940 ]. Funding Information: We are deeply grateful to the women and hospitals which participated in the study and to: Reina Collado for administrative support, Rosa Maria Garcia Hern?ndez and Michael Kopplin for technical assistance in the process of measuring urinary creatinine and arsenic concentrations. This study was supported by CONACyT, Fondo Sectorial de Investigaci?n en Salud y Seguridad Social [2005-2-14373, 2009-1-111384, 2010-1-140962 and 2016?272632]. Additional support was provided in part by The Dean Carter Binational Center for Environmental Health Sciences (University of Arizona) and the NIEHS Superfund Research Program [ES 04940]. Publisher Copyright: © 2020
PY - 2020/5
Y1 - 2020/5
N2 - Background: Previously 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. Methods: A 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. Results: Urinary 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). Conclusion: Altered 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.
AB - Background: Previously 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. Methods: A 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. Results: Urinary 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). Conclusion: Altered 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.
KW - Breast cancer
KW - HER2
KW - Hormonal receptor
KW - Inorganic arsenic
KW - Triple negative
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U2 - 10.1016/j.envres.2020.109361
DO - 10.1016/j.envres.2020.109361
M3 - Article
C2 - 32209496
SN - 0013-9351
VL - 184
JO - Environmental Research
JF - Environmental Research
M1 - 109361
ER -