Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
Prevention and Cancer Control, Cancer Care Ontario, Ontario Health, Toronto, ON, Canada.
Int J Cancer. 2020 Sep 1;147(5):1354-1373. doi: 10.1002/ijc.32906. Epub 2020 Feb 25.
Iron has been suggested to contribute to breast cancer development through oxidative stress generation. Our study investigated associations between iron intake and breast cancer risk, overall and by menopausal and estrogen receptor/progesterone receptor (ER/PR) status, and modification by oxidative stress-related genetic polymorphisms (MnSOD, GSTM1 and GSTT1). A population-based case-control study (3,030 cases and 3,402 controls) was conducted in Ontario, Canada. Iron intake (total, dietary, supplemental, heme, nonheme) was assessed using a validated food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from multivariable logistic regression models. Interactions between iron intake and genotypes were assessed among 1,696 cases and 1,761 controls providing DNA. Overall, no associations were observed between iron intake and breast cancer risk. Among premenopausal women, total, dietary and dietary nonheme iron were positively associated with ER-/PR- breast cancer risk (all p < 0.05). Among postmenopausal women, supplemental iron was associated with reduced breast cancer risk (OR = 0.68, 95% CI: 0.51-0.91), and dietary heme iron was associated with an increased risk, particularly the ER-/PR- subtype (OR = 1.69, 95% CI: 1.16-2.47; p = 0.02). Furthermore, GSTT1 and combined GSTM1/GSTT1 polymorphisms modified some of the associations. For example, higher dietary iron was most strongly associated with increased breast cancer risk among women with GSTT1 deletion or GSTM1/GSTT1 double deletions (p < 0.05). Findings suggest that iron intake may have different effects on breast cancer risk according to menopausal and hormone receptor status, as well as genotypes affecting antioxidant capacity.
铁已被认为通过产生氧化应激而促进乳腺癌的发展。我们的研究调查了铁摄入与乳腺癌风险之间的关联，包括总体关联以及绝经前后和雌激素受体/孕激素受体（ER/PR）状态的关联，并探讨了与氧化应激相关的遗传多态性（MnSOD、GSTM1 和 GSTT1）的修饰作用。在加拿大安大略省进行了一项基于人群的病例对照研究（3030 例病例和 3402 例对照）。使用经过验证的食物频率问卷评估铁摄入（总摄入量、膳食摄入量、补充剂摄入量、血红素、非血红素）。使用多变量逻辑回归模型估计比值比（OR）和 95%置信区间（CI）。在提供 DNA 的 1696 例病例和 1761 例对照中，评估了铁摄入与基因型之间的相互作用。总体而言，铁摄入与乳腺癌风险之间没有关联。在绝经前妇女中，总摄入量、膳食摄入量和膳食非血红素铁与 ER-/PR-乳腺癌风险呈正相关（均 p < 0.05）。在绝经后妇女中，补充铁与乳腺癌风险降低相关（OR = 0.68，95%CI：0.51-0.91），膳食血红素铁与风险增加相关，尤其是 ER-/PR-亚型（OR = 1.69，95%CI：1.16-2.47；p = 0.02）。此外，GSTT1 和联合 GSTM1/GSTT1 多态性修饰了一些关联。例如，在 GSTT1 缺失或 GSTM1/GSTT1 双重缺失的女性中，膳食铁摄入量与乳腺癌风险增加的相关性最强（p < 0.05）。研究结果表明，根据绝经和激素受体状态以及影响抗氧化能力的基因型，铁摄入可能对乳腺癌风险有不同的影响。
