Thompson Henry J, Neil Elizabeth S, McGinley John N
Cancer Prevention Laboratory, Colorado State University, Fort Collins, CO 80523, USA.
Biomedicines. 2021 Nov 9;9(11):1652. doi: 10.3390/biomedicines9111652.
Population studies, systematic reviews, and meta-analyses have revealed no relationship between iron status and breast cancer, a weak positive association, or a small protective effect of low iron status. However, in those studies, the authors concluded that further investigation was merited. The set of experiments reported here used preclinical models to assess the likely value of further investigation. The effects of iron status on the initiation and promotion stage of mammary carcinogenesis are reported. Using the classical model of cancer initiation in the mammary gland, 7,12 dimethyl-benz[α]anthracene-induced carcinogenesis was unaffected by iron status. Similarly, excess iron intake showed no effect on the promotion stage of 1-methyl-1-nitrosurea-induced mammary carcinogenesis, though iron deficiency exerted a specific inhibitory effect on the carcinogenic process. Though iron-mediated cellular oxidation is frequently cited as a potential mechanism for effects on breast cancer, no evidence of increased oxidative damage to DNA attributable to excess iron intake was found. The reported preclinical data fail to provide convincing evidence that the further evaluation of the iron-breast cancer risk hypotheses is warranted and underscore the value of redefining the referent group in population-based studies of iron-cancer hypotheses in other tissues.
人群研究、系统评价和荟萃分析表明，铁状态与乳腺癌之间不存在关联、存在微弱的正相关或低铁状态有较小的保护作用。然而，在这些研究中，作者得出结论认为值得进一步研究。本文报道的一系列实验使用临床前模型来评估进一步研究的可能价值。报告了铁状态对乳腺癌发生起始和促进阶段的影响。使用经典的乳腺肿瘤起始模型，7,12-二甲基苯并[a]蒽诱导的肿瘤发生不受铁状态的影响。同样，过量摄入铁对1-甲基-1-亚硝基脲诱导的乳腺癌发生促进阶段没有影响，尽管缺铁对致癌过程有特定的抑制作用。尽管铁介导的细胞氧化经常被认为是影响乳腺癌的潜在机制，但未发现因过量摄入铁导致DNA氧化损伤增加的证据。报道的临床前数据未能提供令人信服的证据表明有必要进一步评估铁与乳腺癌风险假说，强调了在基于人群的其他组织中铁与癌症假说研究中重新定义参照组的价值。
