Genetic variation and circulating levels of IGF-I and IGFBP-3 in relation to risk of proliferative benign breast disease.
Genetic variation and circulating levels of IGF-I and IGFBP-3 in relation to risk of proliferative benign breast disease.
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DOI：
10.1002/ijc.24674
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发表时间：
2010-01-01
影响因子：
6.4
通讯作者：
Tamimi, Rulla M.
中科院分区：
文献类型：
--
作者：
Su, Xuefen;Colditz, Graham A.;Willett, Walter C.;Collins, Laura C.;Schnitt, Stuart J.;Connolly, James L.;Pollak, Michael N.;Rosner, Bernard;Tamimi, Rulla M.
胰岛素样生长因子-I（IGF-I）及其主要结合蛋白IGFBP-3与乳腺癌的发生有关。我们在护士健康研究II（NHSII）中检查了遗传变异和IGF-I和IGFBP-3循环水平与良性增生性乳腺疾病（BBD）（乳腺癌风险增加的标志物）之间的关联。参与者为359例病理证实的增殖性BBD病例和359例匹配对照。循环IGF-I和IGFBP-3水平在1996年至1999年收集的血液样本中进行了测量。使用单倍型标签法选择IGF-I、IGFBP-1和IGFBP-3基因中的30个单核苷酸多态性（SNP），并在病例组和对照组中进行基因分型。循环IGF-I水平与增殖性BBD风险无关。较高的循环IGFBP-3水平与增殖性BBD风险增加显著相关（最高与最低四分位比值比（OR）（95%置信区间（CI）），1.70（1.06-2.72）; p趋势= 0.03）。两种IGFBP-3 SNP的次要等位基因与较低的增殖性BBD风险相关（纯合变体与纯合野生型OR（95% CI）：rs3110697：0.6（0.4-0.9），p-trend = 0.02; rs 2132570：0.2（0.1-0.6），p-trend = 0.02）。其他三种IGFBP-3 SNP（rs 2854744、rs 2960436和rs 2854746）与循环IGFBP-3水平显著相关（p < 0.01）。尽管这些SNP与增殖性BBD风险无显著相关性，但有证据表明，与较高循环IGFBP-3水平相关的等位基因也与增殖性BBD的较高风险相关。这些结果表明，IGFBP-3的遗传变异和循环水平可能在乳腺癌发生的早期阶段发挥作用。
Insulin-like growth factor-I (IGF-I) and its major binding protein IGFBP-3 have been implicated in breast carcinogenesis. We examined the associations between genetic variants and circulating levels of IGF-I and IGFBP-3 with proliferative benign breast disease (BBD), a marker of increased breast cancer risk, in the Nurses’ Health Study II (NHSII). Participants were 359 pathology-confirmed proliferative BBD cases and 359 matched controls. Circulating IGF-I and IGFBP-3 levels were measured in blood samples collected between 1996 and 1999. Thirty single nucleotide polymorphisms (SNPs) in IGF-I, IGFBP-1, and IGFBP-3 genes were selected using a haplotype tagging approach and genotyped in cases and controls. Circulating IGF-I levels were not associated with proliferative BBD risk. Higher circulating IGFBP-3 levels were significantly associated with increased risk of proliferative BBD (highest vs. lowest quartile odds ratio (OR) (95% confidence interval (CI)), 1.70 (1.06–2.72); p-trend = 0.03). The minor alleles of two IGFBP-3 SNPs were associated with lower proliferative BBD risk (homozygous variant vs. homozygous wild-type OR (95% CI): rs3110697: 0.6 (0.4–0.9), p-trend = 0.02; rs2132570: 0.2 (0.1–0.6), p-trend = 0.02). Three other IGFBP-3 SNPs (rs2854744, rs2960436, and rs2854746) were significantly associated with circulating IGFBP-3 levels (p < 0.01). Although these SNPs were not significantly associated with proliferative BBD risk, there was suggestive evidence that the alleles associated with higher circulating IGFBP-3 levels were also associated with higher risk of proliferative BBD. These results suggest that genetic variants and circulating levels of IGFBP-3 may play a role in the early stage of breast carcinogenesis.
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