A sequence repeat in the insulin-like growth factor-1 gene and risk of breast cancer
A sequence repeat in the insulin-like growth factor-1 gene and risk of breast cancer
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DOI：
10.1002/ijc.10473
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发表时间：
2002-07-20
影响因子：
6.4
通讯作者：
Hankinson, SE
中科院分区：
文献类型：
--
作者：
Missmer, SA;Haiman, CA;Hankinson, SE
胰岛素样生长因子-I（IGF-I）是一种有效的有丝分裂原，被假设影响乳腺癌的风险。在3项既往研究中，IGF-1基因多态性（序列重复长度）与血浆IGF-I水平相关。我们在护士健康研究中进行的一项巢式病例对照研究中，前瞻性评估了IGF-I基因a（CA）（n）重复多态性、IGF-I水平和乳腺癌风险之间的关系。1989 - 1990年收集了血液样本;截至1994年6月，我们确定了463例乳腺癌。每个病例选择1 - 2个对照，按年龄、绝经状态、绝经后激素使用、采血月份和时间以及空腹状态匹配，共622个对照。尽管未观察到显著趋势，但与19（CA）（n）重复长度纯合子（分别为146和173 ng/ml;成对平均值比较的pi值= 0.005）相比，无19等位基因拷贝的对照组血浆IGF-I水平显著较低。在条件Logistic回归分析中，控制已建立的乳腺癌危险因素，我们观察到（CA）（n）重复长度基因型与乳腺癌的危险性之间没有显著的关联[与重复基因型19/ 19-18/19相比，基因型相对危险度（RR）= 0.96，95%可信区间（0）= 0.56-1.64; 18120基因型RR = 0.92，95% CI = 0.39-2.19，19/20基因型RR = 1.16，95% CI = 0.821.64，19/21基因型RR = 0.69，95% CI = 0.42-1.14; 20/20基因型RR = 0.55，95%CI = 0.28-1.10; 20/21基因型RR = 0.72，95%CI = 0.29-1.79]。根据绝经状态、肿瘤受体状态或其他乳腺癌危险因素的类别进行评价时，结果没有显著差异。虽然不能排除适度的关联，但我们的数据不支持IGF-I基因多态性与乳腺癌风险之间的重要关系。(C)2002年威利-利斯。
Insulin-like growth factor-I (IGF-I), a potent mitogen, is hypothesized to influence breast cancer risk. In 3 previous studies, a polymorphism in the IGF-1 gene (sequence repeat length) was associated with plasma IGF-I level. We evaluated prospectively the relationships among a (CA)(n) repeat polymorphism in the IGF-I gene, IGF-I level and breast cancer risk in a nested case-control study conducted within the Nurses' Health Study. Blood samples were collected in 19891990; up to June 1994, we identified 463 cases of breast cancer. One to 2 controls were selected per case, matched by age, menopausal status, postmenopausal hormone use, month and time of day of blood collection and fasting status, for a total of 622 controls. Although no significant trend was observed, plasma IGF-I levels were significantly lower among controls, with no copy of the 19 allele, compared with those homozygous for the 19 (CA)(n) repeat length (146 and 173 ng/ml, respectively; pi-value for pairwise mean comparison = 0.005). In conditional logistic regression, controlling for established breast cancer risk factors, we observed no significant association between (CA)(n) repeat length genotype and risk of breast cancer [compared with repeat genotype 19/ 19-18/19 genotype relative risk (RR) = 0.96, 95% confidence interval (0) = 0.56-1.64; 18120 genotype RR = 0.92, 95% CI = 0.39-2.19; 19/20 genotype RR = 1.16, 95% CI = 0.821.64; 19/21 genotype RR = 0.69, 95% CI = 0.42-1.14; 20/20 genotype RR = 0.55, 95% CI = 0.28-1.10; 20/21 genotype RR = 0.72, 95% CI = 0.29-1.79]. Results did not vary substantially when evaluated according to menopausal status, tumor receptor status or category of other breast cancer risk factors. Although a modest association cannot be excluded, our data do not support an important relation between this IGF-I gene polymorphism and breast cancer risk. (C) 2002 Wiley-Liss.