背景:本研究的目的是探索不同血清铁状态之间的因果关系(铁蛋白,转铁蛋白,转铁蛋白饱和度,和血清铁)以及雌激素受体(ER)阳性或ER阴性乳腺癌的发生。
方法:血清铁状态暴露的汇总数据来自IEUOpenGWAS项目,英国生物银行,和其他数据库。同时,ER+和ER-乳腺癌的汇总数据来自乳腺癌协会联盟(BCAC).通过检查铁状态和乳腺癌之间的因果关系,我们部署了五种不同的孟德尔随机化(MR)算法,即MR-Egger,逆方差加权(IVW),加权中位数,简单模式,MR-PRESSO为了评估异质性和水平多效性,应用了Cochran的Q和MR-Egger算法,分别。
结果:铁蛋白水平升高与ER阴性乳腺癌风险增加相关(OR(IVW)=1.042,95%CI(1.005,1.081),p=0.025;OR(加权中位数)=1.050,95%CI(1.001,1.102),p=0.046;OR(MR-PRESSO)=1.042,95%CI(1.005,1.081),p=0.039)。相反,血清铁水平的升高与ER阴性乳腺癌的风险降低有关(OR(IVW)=0.791,95%CI(0.649,0.962),p=0.019;OR(MR-PRESSO)=0.791,95%CI(0.649,0.962),p=0.028)。然而,没有证据表明转铁蛋白之间存在因果关系,转铁蛋白饱和度,和ER阴性乳腺癌。对于ER阳性乳腺癌,四种不同的铁状态均无因果关系.
结论:铁蛋白与ER阴性乳腺癌呈正相关,而血清铁与ER阴性乳腺癌呈负相关。然而,四种铁状态与ER阳性乳腺癌之间没有因果关系.
BACKGROUND: The aim of this study was to explore the causal relationship between different serum
iron statuses (ferritin, transferrin, transferrin saturation, and serum
iron) and the occurrence of estrogen receptor (ER)-positive or ER-negative breast cancer.
METHODS: The summary data on serum
iron status exposure were gathered from the IEU OpenGWAS Project, the UK Biobank, and other databases. Concurrently, the summary data for ER+ and ER- breast cancer are sourced from the Breast Cancer Association Consortium (BCAC). By examining the causal link between
iron status and breast cancer, we deployed five distinct Mendelian randomization (MR) algorithms, namely MR-Egger, inverse variance weighted (IVW), weighted median, simple mode, and MR-PRESSO. To assess heterogeneity and horizontal pleiotropy, Cochran\'s Q and MR-Egger algorithms were applied, respectively.
RESULTS: Elevated ferritin levels are associated with an increased risk of ER-negative breast cancer (OR(IVW) = 1.042, 95% CI (1.005, 1.081), p = 0.025; OR (weighted median) = 1.050, 95% CI (1.001, 1.102), p = 0.046; and OR (MR-PRESSO) = 1.042, 95% CI (1.005, 1.081), p = 0.039). Conversely, an increase in the serum iron level is linked to a reduced risk of ER-negative breast cancer (OR (IVW) = 0.791, 95% CI (0.649, 0.962), p = 0.019; and OR (MR-PRESSO) = 0.791, 95% CI (0.649, 0.962), p = 0.028). However, there is no evidence of a causal relationship between transferrin, transferrin saturation, and ER-negative breast cancer. For ER-positive breast cancer, none of the four different iron statuses demonstrated a causal relationship.
CONCLUSIONS: Ferritin is positively correlated with ER-negative breast cancer, while serum iron is negatively associated with ER-negative breast cancer. However, there is no causal relationship between the four
iron statuses and ER-positive breast cancer.