Implications for prostate cancer of insulin-like growth factor-I (IGF-I) genetic variation and circulating IGF-I levels
Implications for prostate cancer of insulin-like growth factor-I (IGF-I) genetic variation and circulating IGF-I levels
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DOI：
10.1210/jc.2007-0887
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发表时间：
2007-12-01
影响因子：
5.8
通讯作者：
Kaaks, Rudolf
中科院分区：
文献类型：
--
作者：
Johansson, Mattias;Mckay, James D.;Kaaks, Rudolf
背景：循环IGF-I水平升高一直与前列腺癌风险增加相关。我们最近在IGF-I基因的3 '区域中发现了与前列腺癌风险增加相关的单倍型，并且我们假设所观察到的关联是由循环IGF-I介导的。我们分析了IGF-I基因3 '区的单倍型和三个单倍型标记的单核苷酸多态性（htSNPs）与循环水平IGF-I的关系。在来自瑞典CAPS研究的698名对照受试者和来自前瞻性北方瑞典健康和疾病队列研究（NSHDC）的575名病例和对照中进行了I。我们还进行了荟萃分析，这两个和其他四个关联研究的IGF-I基因的3 '区域的遗传变异与循环IGF-I levels.Results：IGF-I单倍型以前与前列腺癌的风险，标记为“TCC”，与IGF-I水平升高在CAPS研究（P = 0.02），但不是在NSHDC研究。相反，标记该单倍型的三个IGF-I htSNP中的两个，rs6220和rs7136446，与NSHDC中IGF-I水平升高相关（分别为P = 0.03和P = 0.04），但在CAPS研究中不相关。在荟萃分析中，TCC单倍型和rs6220 SNP与循环IGF-I水平升高相关（分别为P = 0.001和P < 0.0001）。结论：IGF-I基因3 '区的遗传变异似乎影响循环IGF-I水平。这一观察结果与IGF-I基因变异通过影响IGF-I循环水平在前列腺癌易感性中发挥作用的假设一致。
Background: Elevated levels of circulating IGF-I have consistently been associated with increased prostate cancer risk. We recently found a haplotype in the 3 ' region of the IGF-I gene associated with increased risk of prostate cancer, and we hypothesized that the observed association is mediated by circulating IGF-I.Materials and Methods: We analyzed haplotypes and three haplotype-tagging single nucleotide polymorphisms (htSNPs) in the 3 ' region of the IGF-I gene in relation to circulating levels IGF-I in 698 control subjects from the CAncer Prostate in Sweden ( CAPS) study and 575 cases and controls from the prospective Northern Sweden Health and Disease Cohort ( NSHDC) study. We also performed a meta-analysis of these two and four other association studies on genetic variation in the 3 ' region of the IGF-I gene in relation to circulating IGF-I levels.Results: The IGF-I haplotype previously associated with prostate cancer risk, labeled "TCC," was associated with elevated levels of IGF-I in the CAPS study (P = 0.02), but not in the NSHDC study. In contrast, two of the three IGF-I htSNPs tagging this haplotype, rs6220 and rs7136446, were associated with elevated levels of IGF-I in the NSHDC ( P = 0.03 and P = 0.04, respectively), but not in the CAPS study. In the meta-analysis, the TCC haplotype and the rs6220 SNP were associated with elevated levels of circulating IGF-I ( P = 0.001 and P < 0.0001, respectively).Conclusions: Genetic variation in the 3 ' region of the IGF-I gene seems to influence circulating levels of IGF-I. This observation is consistent with the hypothesis that variation in the IGF-I gene plays a role in prostate cancer susceptibility by influencing circulating levels of IGF-I.