Three Authors Reply.
Three Authors Reply.
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三位作者回复。
DOI：
10.1093/aje/kwv119
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发表时间：
2015
影响因子：
5
通讯作者：
Smith,AllanH
中科院分区：
文献类型：
--
作者：
Steinmaus,Craig;Ferreccio,Catterina;Smith,AllanH
我们同意Slim和Sewitch（1）试图表达的总体概念：像我们这样重要的新发现应该被批判性地审查，至少在最初，谨慎地解释。值得注意的是，我们的研究是第一个基于个人的终生暴露数据，以确定饮用水中砷浓度低于100微克/升与肺癌风险增加之间的关联（2）。鉴于这种新奇，我们认为同样重要的是要注意我们的研究结果符合几个通常用于评估因果关系的标准（3）。例如，我们在几项分析中发现了剂量反应关系的证据。我们还发现了非常低的P值，这表明我们的一些发现不太可能是偶然的。我们还报道了吸烟、饮食、职业或其他肺癌风险的主要决定因素的混杂并没有导致我们的结果的证据。关于一致性和生物相容性的因果标准，我们引用的数据表明，砷到达我们的靶器官部位（肺），并在那里引起毒性。我们还引用了一些文献，其中表明砷在较高暴露水平下是肺癌的一个公认原因，并且在其他研究中发现了与我们相似的长潜伏期模式。此外，我们没有理由相信Slim和Sewitch提出的具体问题导致了我们的结果。例如，在暴露水平较高和较低的地区使用完全相同的方法确定病例;我们引用了以前提供的数据，这些数据表明我们在研究地区的对照分布与智利人口普查中的分布相似（4）;我们40年潜伏期分析中的每个人都是40岁或以上;我们的主要发现的重要性在去除了代理主体后只有轻微的变化（我们的文章（2）的网络表3），在任何情况下，对于砷暴露，代理访谈只需确定居住的城市或城镇;我们明确指出，受试者是频率匹配的（而不是1：1匹配的），因此无条件logistic回归是适当的选择。关于我们的标题，我们的研究是关于低砷暴露和我们发现的癌症风险增加的关联。正因为如此，我们认为我们的标题是非常合适的。至于我们的发现可能引起的“公众恐惧”和“警报”：我们认为，我们的发现至少应该引起人们对低水平砷暴露导致癌症的可能性的关注，这种可能性不应该被简单地忽视。虽然我们无法控制每个人对我们的发现的反应，但我们相信大多数人会接受它们，以及我们的结论所述的，即“新证据表明砷水浓度低于100微克/升与肺癌风险增加有关”（2，第1082页）。总的来说，我们认为，谨慎的做法是仔细考虑这些调查结果，不要因为虚假的方法问题而将其排除在外。
We agree with the overall concept that we believe Slim and Sewitch (1) are trying to express: Important novel findings like ours should be critically reviewed and, at least initially, interpreted cautiously. Notably, our study was the first with individual-based data on lifetime exposures to identify an association between arsenic concentrations below 100 µg/L in drinking water and increased risks of lung cancer (2). Given this novelty, we believe it is also important to note that our findings met several of the criteria commonly used to evaluate causality (3). For example, we found evidence of dose-response relationships in several of our analyses. We also found very low P values, which suggests that several of our findings are unlikely to be due to chance. We also reported evidence that confounding by smoking, diet, occupation, or other major determinants of lung cancer risk did not cause our results. With regard to the causal criteria of consistency and biologic plausibility, we cited data showing that arsenic reaches our target organ site (the lung) and that it causes toxicity there. We also cited literature in which it was shown that arsenic is a well-established cause of lung cancer at higher exposure levels and that long latency patterns similar to ours have been found in other studies. In addition, we have no reason to believe the specific issues raised by Slim and Sewitch caused our results. For example, cases were ascertained using the exact same methods in areas with higher and lower levels of exposure; we cited previously presented data that showed that the distribution of our controls in the study area was similar to that in the Chilean census (4); everyone in our 40-year latency analysis was 40 years of age or older; the magnitude of our major findings changed only slightly when proxy subjects were removed (Web Table 3 of our article (2)) and in any case, for arsenic exposure, the proxy interviews only had to identify city or town of residence; and we clearly stated that the subjects were frequency matched (versus 1: 1 matched) so that unconditional logistic regression is the appropriate choice.With regard to our title, our study was about low arsenic exposures and the associations we found with increased cancer risks. Because of this, we believe our title is quite appropriate. As for the “public fear” and “alarm” that our findings might induce: We believe that our findings should raise at least some concern about the possibility that low-level arsenic exposures cause cancer and that this possibility should not simply be ignored. Although we cannot control everyone's reaction to our findings, we believe that most people will take them for what they are and for what our conclusion stated them to be, that is,“new evidence that arsenic water concentrations less than 100 µg/L are associated with increased risks of lung cancer”(2, p. 1082). Overall, we believe it is prudent to consider these findings carefully and not to dismiss them because of spurious methodological issues.