Associations of insulin-like growth factor and insulin-like growth factor binding protein-3 with mortality in women with breast cancer.
Associations of insulin-like growth factor and insulin-like growth factor binding protein-3 with mortality in women with breast cancer.
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DOI：
10.1002/ijc.27753
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发表时间：
2013-03-01
影响因子：
6.4
通讯作者：
McTiernan, Anne
中科院分区：
文献类型：
--
作者：
Duggan, Catherine;Wang, Ching-Yun;Neuhouser, Marian L.;Xiao, Liren;Smith, Ashley Wilder;Reding, Kerryn W.;Baumgartner, Richard N.;Baumgartner, Kathy B.;Bernstein, Leslie;Ballard-Barbash, Rachel;McTiernan, Anne
升高的循环胰岛素样生长因子-1（IGF-1），乳腺上皮细胞有丝分裂原，与乳腺癌的发展有关。然而，它与乳腺癌生存率的关系尚未建立。IGF-1的循环浓度通过结合蛋白控制，包括IGF结合蛋白-3（IGFBP-3），其可以调节IGF 1与乳腺癌结局的关联。我们测量了600名参加健康、饮食、活动和生活方式（HEAL）研究的女性血清中的IGF-1和IGFBP-3浓度，该研究是一项多种族的前瞻性队列研究，研究对象是诊断为I-IIIA期乳腺癌的女性。我们评估了IGF-1和IGFBP-3之间的相关性，并使用考克斯比例风险模型，使用五分位数临界点建模，乳腺癌特异性（n=42例死亡）和全因死亡率（n=87例死亡）风险。在校正了体重指数、种族、抽血时他莫昔芬使用、诊断时接受的治疗和IGFBP-3的模型中，IGF-1水平最高五分位数的女性全因死亡风险增加（风险比（HR）=3.10 95%CI 1.21-7.93，p=0.02），尽管没有明显的剂量反应相关性。在完全校正的模型中，IGF-1/IGFBP-3比值（游离IGF-I水平的指标）与全因死亡风险增加显著相关（HR=2.83 95%CI 1.25-6.36 Ptrend=0.01，上五分位数vs下五分位数）。总之，高血清IGF-1水平和IGF-1/IGFBP-3比值与乳腺癌女性全因死亡风险增加相关。这些结果需要在更大的乳腺癌幸存者队列中得到证实。
Elevated circulating insulin-like growth factor-1 (IGF-1), a breast epithelial cell mitogen, is associated with breast cancer development. However, its association with breast cancer survival is not established. Circulating concentrations of IGF-1 are controlled via binding proteins, including IGF Binding Protein-3 (IGFBP-3), that may modulate the association of IGF1 with breast-cancer outcomes. We measured IGF-1 and IGFBP-3 concentrations in serum from 600 women enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study, a multiethnic, prospective cohort study of women diagnosed with stage I-IIIA breast cancer. We evaluated the association between IGF-1 and IGFBP-3, and as a ratio, modeled using quintile cut-points, with risk of breast cancer-specific (n=42 deaths) and all-cause mortality (n=87 deaths) using Cox proportional hazards models. In models adjusted for body mass index, ethnicity, tamoxifen use at time of blood draw, treatment received at diagnosis, and IGFBP-3, women in the highest quintile of IGF-1 level had an increased risk of all-cause mortality (Hazard Ratio (HR)=3.10 95% CI 1.21-7.93, p=0.02), although no dose-response association was evident. The IGF-1/IGFBP-3 ratio, an indicator of free IGF-I levels, was significantly associated with increasing risk of all-cause mortality (HR=2.83 95% CI 1.25-6.36 Ptrend=0.01, upper vs. lower quintile) in a fully adjusted model. In conclusion, high serum levels of IGF-1 and the IGF-1/IGFBP-3 ratio were associated with increased risk of all-cause mortality in women with breast cancer. These results need to be confirmed in larger breast cancer survivor cohorts.
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影响因子：
51.1
作者：
Key, Timothy J.;Appleby, Paul N.;Reeves, Gillian K.;Roddam, Andrew W.
通讯作者：
Roddam, Andrew W.
影响因子：
45.3
作者：
Maki, Robert G.
通讯作者：
Maki, Robert G.
影响因子：
6.4
作者：
Keinan-Boker, L;de Mesquita, HBB;Peeters, PHM
通讯作者：
Peeters, PHM
影响因子：
3.9
作者：
Al-Delaimy, Wael K.;Flatt, Shirley W.;Pierce, John P.
通讯作者：
Pierce, John P.
影响因子：
45.3
作者：
Goodwin, PJ;Ennis, M;Hood, N
通讯作者：
Hood, N