Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies.
Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies.
复制标题
DOI：
10.1016/s1470-2045(10)70095-4
复制
发表时间：
2010-06
期刊：
影响因子：
51.1
通讯作者：
Roddam, Andrew W.
中科院分区：
文献类型：
--
作者：
Key, Timothy J.;Appleby, Paul N.;Reeves, Gillian K.;Roddam, Andrew W.
胰岛素样生长因子1（IGF 1）刺激有丝分裂并抑制细胞凋亡。一些已发表的结果表明，循环IGF 1和乳腺癌风险之间存在关联，但目前尚不清楚这种关系是否一致，或者是否受到IGF结合蛋白3（IGFBP 3），绝经状态，雌激素受体状态或其他因素的影响。IGF 1（和IGFBP 3）与乳腺癌风险因素的关系也不清楚。内源性激素与乳腺癌协作组的成立是为了分析前瞻性研究的汇总个体数据，以提高内源性激素与乳腺癌风险估计相关性的精确度。从12个国家的17项前瞻性研究中获得了诊断前IGF 1和IGFBP 3浓度的个体数据。通过计算这些因素类别的几何平均浓度，研究了IGF 1与对照组乳腺癌危险因素的相关性。在4790例病例和9428例匹配对照中，通过条件logistic回归估计乳腺癌与IGF 1浓度增加相关的比值比（OR）和95%CI，并按研究、基线年龄和基线日期分层。所有统计检验均为双侧检验，p值小于0.05视为显著。IGF 1浓度，调整年龄，正相关的身高和年龄在第一次怀孕，负相关的初潮年龄和绝经后的年数，并在中度超重的妇女和中度饮酒者高于其他妇女。IGF 1浓度最高与最低五分之一的女性患乳腺癌的OR为1.28（95%CI 1.14 - 1.44; p<0.0001）。调整IGFBP 3并没有改变这种关联，并且在采血时绝经状态也没有显著变化。对于雌激素受体阳性肿瘤和雌激素受体阴性肿瘤，最高和最低五分之一之间IGF 1浓度差异的OR分别为1.38（95%CI 1.14 - 1.68）和0.80（0.57 - 1.13）（异质性p = 0.007）。循环IGF 1与乳腺癌风险呈正相关。这种关联并没有被IGFBP 3实质性地改变，并且在绝经状态下没有显著差异，但似乎仅限于雌激素受体阳性肿瘤。英国癌症研究所。
Insulin-like growth factor 1 (IGF1) stimulates mitosis and inhibits apoptosis. Some published results have shown an association between circulating IGF1 and breast-cancer risk, but it has been unclear whether this relationship is consistent or whether it is modified by IGF binding protein 3 (IGFBP3), menopausal status, oestrogen receptor status or other factors. The relationship of IGF1 (and IGFBP3) with breast-cancer risk factors is also unclear. The Endogenous Hormones and Breast Cancer Collaborative Group was established to analyse pooled individual data from prospective studies to increase the precision of the estimated associations of endogenous hormones with breast-cancer risk. Individual data on prediagnostic IGF1 and IGFBP3 concentrations were obtained from 17 prospective studies in 12 countries. The associations of IGF1 with risk factors for breast cancer in controls were examined by calculating geometric mean concentrations in categories of these factors. The odds ratios (ORs) with 95% CIs of breast cancer associated with increasing IGF1 concentrations were estimated by conditional logistic regression in 4790 cases and 9428 matched controls, with stratification by study, age at baseline, and date of baseline. All statistical tests were two-sided, and a p value of less than 0·05 was considered significant. IGF1 concentrations, adjusted for age, were positively associated with height and age at first pregnancy, inversely associated with age at menarche and years since menopause, and were higher in moderately overweight women and moderate alcohol consumers than in other women. The OR for breast cancer for women in the highest versus the lowest fifth of IGF1 concentration was 1·28 (95% CI 1·14–1·44; p<0·0001). This association was not altered by adjusting for IGFBP3, and did not vary significantly by menopausal status at blood collection. The ORs for a difference in IGF1 concentration between the highest and lowest fifth were 1·38 (95% CI 1·14–1·68) for oestrogen-receptor-positive tumours and 0·80 (0·57–1·13) for oestrogen-receptor-negative tumours (p for heterogeneity=0·007). Circulating IGF1 is positively associated with breast-cancer risk. The association is not substantially modified by IGFBP3, and does not differ markedly by menopausal status, but seems to be confined to oestrogen-receptor-positive tumours. Cancer Research UK.