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 (OR_{MMA/iAs continuous} = 2.03, 95% CI: 1.33–3.10). A significant negative association was observed between DMA/MMA and HR + BC (OR_{DMA/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.

中文翻译：

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墨西哥北部女性的免疫组化亚型的无机砷甲基化能力和乳腺癌。

背景

先前我们报道无机砷（iAs）甲基化能力与乳腺癌（BC）有关。BC危险因素可能会根据免疫组织化学亚型而有所不同。在这里，我们探讨了亚型甲基化iAs的能力与BC风险之间的关系。

方法

在墨西哥北部进行了基于人群的病例对照研究。具有BC亚型可用信息的患者（n = 499）与健康对照者年龄匹配。获得了社会人口统计学，生殖和生活方式特征。肿瘤标志物信息是从医疗记录中获得的。病例分为HR + [雌激素受体（ER +）和/或孕激素（PR +）和人表皮生长因子受体2（HER2-）]，HER2 +或三阴性（TN）。通过高效液相色谱-电感耦合等离子体质谱法（HPLC-ICP-MS）测定尿中砷的种类，并计算甲基化能力参数。使用条件逻辑回归模型按亚型估算BC风险。

结果

尿中总砷含量在0.60至303.29μg/ L之间。发现单甲基ar酸％（％MMA）与HR + BC之间存在显着的正相关性：百分之一的增加导致OR _％MMA连续 = 2.73，95％CI：1.48，5.05），即使％iAs或％将二甲基亚砷酸（％DMA）添加到具有％MMA的模型中。MMA / iAs与HR + BC呈正相关（OR _{MMA / iAs连续} = _2.03，95％CI：1.33–3.10）。在DMA / MMA与HR + BC之间观察到显着的负相关性（OR _{DMA / MMA连续} = 0.43，95％CI：0.26，0.71）。MMA / iAs与TN BC正相关（或_{MMA / iAs连续} = 4.05; 95％CI：_1.63，10.04）。

结论

导致更高的％MMA的iAs甲基化能力改变与HR +和TN BC有关，而与HER2 +不相关。MMA是iAs代谢产物，更可能与BC相关。需要进一步的研究来确认这些结果并阐明潜在的生物学机制。