Hemochromatosis gene mutations, body iron stores, dietary iron, and risk of colorectal adenoma in women
Hemochromatosis gene mutations, body iron stores, dietary iron, and risk of colorectal adenoma in women
复制标题
DOI：
10.1093/jnci/dji165
复制
发表时间：
2005-06-15
影响因子：
10.3
通讯作者：
Fuchs, CS
中科院分区：
文献类型：
--
作者：
Chan, AT;Ma, J;Fuchs, CS
背景一些实验证据表明，铁可能在结直肠癌发生中发挥作用，但这一作用的人类数据一直相互矛盾，可能是因为与研究设计或铁暴露测量相关的问题。我们对参加护士健康研究的妇女进行了一项前瞻性、巢式病例对照研究，评估了膳食铁摄入量和铁状况的遗传和生化标志物。研究方法：在32826名提供血液标本的妇女中，我们确定了527名患有结直肠腺瘤的妇女和527名接受内窥镜检查但在采血后未被诊断为腺瘤的对照组。我们评估了铁摄入量，与遗传性血色病相关的HFE基因突变（即，H63 D和C282 Y），以及全身铁的血浆生化测量，包括转铁蛋白饱和度和转铁蛋白受体与铁蛋白的浓度比。Logistic回归模型用于估计相对危险度（RR）和95%置信区间（CI）。所有统计检验均为双侧检验。结果如下：与没有HFE基因突变的女性相比，具有任何HFE基因突变的女性具有更高的全身铁储存，这反映在更高的转铁蛋白饱和度（P <0.001）和更低的转铁蛋白受体与铁蛋白的比率（P = 0.02）。然而，HFE基因突变与腺瘤风险无关（多变量RR = 1.08，95%CI = 0.83 - 1.39; P = 0.58）。此外，极端类别的比较显示腺瘤和转铁蛋白饱和程度之间没有关联（多变量RR = 0.96，95% CI = 0.63至1.47; P趋势= 0.66），转铁蛋白受体与铁蛋白的比值（多变量RR = 0.98，95% CI，0.60至1.60; P趋势= 0.99）或膳食铁摄入量（多变量RR = 1.04，95% CI = 0.68至1.57; P趋势= 0.94）。结论：虽然我们的研究使用了几种不同的铁状态测量方法（即，基因突变、生化标志物和饮食摄入）和巢式病例对照设计，我们没有观察到铁在女性结直肠肿瘤发病中的作用。
Background. Some experimental evidence suggests that iron may play a role in colorectal carcinogenesis, but human data for this role have been conflicting, possibly because of problems related to study design or measurement of iron exposure. We assessed dietary iron intake and genetic and biochemical markers of iron status in a prospective, nested case-control study of women enrolled in the Nurses' Health Study. Methods: Among 32826 women who provided a blood specimen, we identified 527 women with colorectal adenoma and 527 matched control subjects who underwent endoscopy but were not diagnosed with adenoma after blood collection. We assessed iron intake, mutations in the HFE gene that are associated with hereditary hemochromatosis (i.e., H63D and C282Y), and plasma biochemical measures of total body iron, including transferrin saturation and the ratio of the concentrations of transferrin receptors to ferritin. Logistic regression models were used to estimate relative risks (RR) and 95% confidence intervals (CI). All statistical tests were two-sided. Results: Women with any HFE gene mutation had higher total body iron stores, as reflected by higher transferrin saturations (P < .001) and lower levels of the ratio of transferrin receptors to ferritin (P = .02), than women with no HFE gene mutation. However, HFE gene mutations were not associated with risk of adenoma (multivariable RR = 1.08, 95% CI = 0.83 to 1.39; P = .58). Moreover, comparison of extreme categories showed no associations between adenoma and the extent of transferrin saturation (multivariable RR = 0.96, 95% Cl = 0.63 to 1.47; P-trend = .66), the ratio of transferrin receptors to ferritin (multivariable RR = 0.98, 95% CI, 0.60 to 1.60; P-trend = .99), or dietary iron intake (multivariable RR = 1.04, 95% Cl = 0.68 to 1.57; P-trend = .94). Conclusions: Although our study used several distinct measures of iron status (i.e., genetic mutations, biochemical markers, and dietary intake) and a nested case-control design, we did not observe a role for iron in the pathogenesis of colorectal neoplasia in women.