Smith Allan H, Marshall Guillermo, Yuan Yan, Steinmaus Craig, Liaw Jane, Smith Martyn T, Wood Lily, Heirich Marissa, Fritzemeier Rebecca M, Pegram Mark D, Ferreccio Catterina
Arsenic Research Group, School of Public Health, University of California, Berkeley, Berkeley, CA (Prof AH Smith MD, Y Yuan MPH, Assoc Prof C Steinmaus MD, J Liaw MPH); Departamento de Estadística, Facultad de Matemáticas, Pontificia Universidad Catòlica de Chile, Santiago, Chile (Prof G Marshall PhD); Environmental Health Sciences, School of Public Health, University of California, Berkeley, Berkeley, CA (Prof MT Smith PhD); Breast Cancer Oncology Program, Stanford Cancer Institute, Stanford, CA (L Wood, M Heirich, RM Fritzemeier MS, Prof MD Pegram MD); Departamento de Salud Pública, Escuela de Medicina, Pontificia Universidad Catòlica de Chile, and Advanced Center for Chronic Diseases ACCDIS, Santiago, Chile (Prof C Ferreccio MD).
EBioMedicine. 2014 Nov 1;1(1):58-63. doi: 10.1016/j.ebiom.2014.10.005.
Arsenic trioxide is effective in treating promyelocytic leukemia, and laboratory studies demonstrate that arsenic trioxide causes apoptosis of human breast cancer cells. Region II in northern Chile experienced very high concentrations of inorganic arsenic in drinking water, especially in the main city Antofagasta from 1958 until an arsenic removal plant was installed in 1970.
We investigated breast cancer mortality from 1950 to 2010 among women in Region II compared to Region V, which had low arsenic water concentrations. We conducted studies on human breast cancer cell lines and compared arsenic exposure in Antofagasta with concentrations inducing apoptosis in laboratory studies.
Before 1958, breast cancer mortality rates were similar, but in 1958-1970 the rates in Region II were half those in Region V (rate ratio RR = 0·51, 95% CI 0·40-0·66; p<0·0001). Women under the age of 60 experienced a 70% reduction in breast cancer mortality during 1965-1970 (RR=0·30, 0·17-0·54; p<0·0001). Breast cancer cell culture studies showed apoptosis at arsenic concentrations close to those estimated to have occurred in people in Region II.
We found biologically plausible major reductions in breast cancer mortality during high exposure to inorganic arsenic in drinking water which could not be attributed to bias or confounding. We recommend clinical trial assessment of inorganic arsenic in the treatment of advanced breast cancer.
三氧化二砷对治疗早幼粒细胞白血病有效,实验室研究表明三氧化二砷可导致人乳腺癌细胞凋亡。智利北部第二大区饮用水中无机砷浓度极高,尤其是在主要城市安托法加斯塔,从1958年到1970年安装除砷厂期间都是如此。
我们调查了第二大区女性在1950年至2010年期间的乳腺癌死亡率,并与砷浓度较低的第五大区进行比较。我们对人乳腺癌细胞系进行了研究,并将安托法加斯塔的砷暴露情况与实验室研究中诱导细胞凋亡的浓度进行了比较。
1958年之前,乳腺癌死亡率相似,但在1958 - 1970年期间,第二大区的死亡率是第五大区的一半(率比RR = 0·51,95%可信区间0·40 - 0·66;p<0·0001)。60岁以下女性在1965 - 1970年期间乳腺癌死亡率降低了70%(RR = 0·30,0·17 - 0·54;p<0·0001)。乳腺癌细胞培养研究表明,在接近估计在第二大区人群中出现的砷浓度时会发生细胞凋亡。
我们发现,在饮用水中高浓度无机砷暴露期间,乳腺癌死亡率出现了生物学上合理的大幅下降,这不能归因于偏倚或混杂因素。我们建议对无机砷治疗晚期乳腺癌进行临床试验评估。