Polymorphisms of genes coding for insulin-like growth factor 1 and its major binding proteins, circulating levels of IGF-I and IGFBP-3 and breast cancer risk: results from the EPIC study.
Polymorphisms of genes coding for insulin-like growth factor 1 and its major binding proteins, circulating levels of IGF-I and IGFBP-3 and breast cancer risk: results from the EPIC study.
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DOI：
10.1038/sj.bjc.6602936
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发表时间：
2006-01-30
影响因子：
8.8
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中科院分区：
文献类型：
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胰岛素样生长因子I（IGF-I）刺激细胞增殖，并可促进不同器官中肿瘤的发展。流行病学研究表明，循环IGF-I水平升高与乳腺癌和其他癌症风险增加有关。大多数循环IGF-I与酸不稳定亚基和六种胰岛素样生长因子结合蛋白（IGFBP）之一结合，其中最重要的是IGFBP-3和IGFBP-1。IGF 1基因和编码主要IGF-I携带者的基因的多态性可以预测IGF-I的循环水平，并对癌症风险产生影响。我们对807例乳腺癌患者和1588例对照组进行了一项病例对照研究，并在欧洲癌症与营养前瞻性调查中对这一假设进行了验证。我们对IGF 1、IGFBP 1、IGFBP 3和IGFALS中23种常见单核苷酸多态性进行了基因分型，并测定了病例组和对照组血清中IGF-I和IGFBP-3的水平。我们发现IGF 1基因5′端的多态性与乳腺癌风险存在微弱但显著的相关性，特别是在55岁以下的女性中，IGFBP 3 5′端的多态性与IGFBP-3的循环水平存在强相关性，这证实了以前的研究结果。这些候选基因中常见的遗传变异在改变高加索人乳腺癌风险方面并不起主要作用。
Insulin-like growth factor I (IGF-I) stimulates cell proliferation and can enhance the development of tumours in different organs. Epidemiological studies have shown that an elevated level of circulating IGF-I is associated with increased risk of breast cancer, as well as of other cancers. Most of circulating IGF-I is bound to an acid-labile subunit and to one of six insulin-like growth factor binding proteins (IGFBPs), among which the most important are IGFBP-3 and IGFBP-1. Polymorphisms of the IGF1 gene and of genes encoding for the major IGF-I carriers may predict circulating levels of IGF-I and have an impact on cancer risk. We tested this hypothesis with a case–control study of 807 breast cancer patients and 1588 matched control subjects, nested within the European Prospective Investigation into Cancer and Nutrition. We genotyped 23 common single nucleotide polymorphisms in IGF1, IGFBP1, IGFBP3 and IGFALS, and measured serum levels of IGF-I and IGFBP-3 in samples of cases and controls. We found a weak but significant association of polymorphisms at the 5′ end of the IGF1 gene with breast cancer risk, particularly among women younger than 55 years, and a strong association of polymorphisms located in the 5′ end of IGFBP3 with circulating levels of IGFBP-3, which confirms previous findings. Common genetic variation in these candidate genes does not play a major role in altering breast cancer risk in Caucasians.
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影响因子：
6.4
作者：
Missmer, SA;Haiman, CA;Hankinson, SE
通讯作者：
Hankinson, SE
影响因子：
56.9
作者：
Chan, JM;Stampfer, MJ;Pollak, M
通讯作者：
Pollak, M
影响因子：
8.8
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影响因子：
4
作者：
Hong, Y;Brismar, K;deFaire, U
通讯作者：
deFaire, U
影响因子：
6.4
作者：
BRUNING, PF;VANDOORN, J;HART, AAM
通讯作者：
HART, AAM