Ose Jennifer, Schock Helena, Poole Elizabeth M, Lehtinen Matti, Visvanathan Kala, Helzlsouer Kathy, Buring Julie E, Lee I-Min, Tjønneland Anne, Boutron-Ruault Marie-Christine, Trichopoulou Antonia, Mattiello Amalia, Onland-Moret N Charlotte, Weiderpass Elisabete, Sánchez María-José, Idahl Annika, Travis Ruth C, Rinaldi Sabina, Merritt Melissa A, Wentzensen Nicolas, Tworoger Shelley S, Kaaks Rudolf, Fortner Renée T
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Baden-Württemberg, Germany.
Department of Population Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Cancer Causes Control. 2017 May;28(5):429-435. doi: 10.1007/s10552-017-0852-8. Epub 2017 Feb 16.
Biologic evidence suggests that the Insulin-like growth factor (IGF)-family may be involved in the etiology of epithelial invasive ovarian cancer (EOC). However, prospective studies investigating the role of IGF-I in ovarian carcinogenesis have yielded conflicting results.
We pooled and harmonized data from 6 case-control studies nested within the Ovarian Cancer Cohort Consortium to investigate the association between pre-diagnosis IGF-I concentrations and subsequent risk of EOC. We evaluated IGF-I concentrations and risk of EOC overall and by tumor subtype (defined by histology, grade, stage) in 1,270 cases and 2,907 matched controls. Multivariable conditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI).
Doubling of IGF-I concentration was associated with significantly lower risk of overall EOC [OR = 0.82; CI 0.72-0.93]. We observed no heterogeneity by tumor characteristics (e.g., histology, p = 0.62), menopausal status at blood collection (p = 0.79), or age at diagnosis (p = 0.60).
These results suggest that IGF-I concentrations are inversely associated with EOC risk, independent of histological phenotype. Future prospective research should consider potential mechanisms for this association, including, considering other members of the IGF-family to better characterize the role of IGF-signaling in the etiology of EOC.
生物学证据表明,胰岛素样生长因子(IGF)家族可能参与上皮性浸润性卵巢癌(EOC)的病因学。然而,调查IGF-I在卵巢癌发生中作用的前瞻性研究结果相互矛盾。
我们汇总并统一了卵巢癌队列联盟中6项病例对照研究的数据,以调查诊断前IGF-I浓度与随后发生EOC风险之间的关联。我们评估了1270例病例和2907例匹配对照中IGF-I的总体浓度以及EOC的风险,并按肿瘤亚型(根据组织学、分级、分期定义)进行评估。使用多变量条件逻辑回归模型计算比值比(OR)和95%置信区间(CI)。
IGF-I浓度翻倍与总体EOC风险显著降低相关[OR = 0.82;CI 0.72 - 0.93]。我们未观察到肿瘤特征(如组织学,p = 0.62)、采血时的绝经状态(p = 0.79)或诊断时年龄(p = 0.60)存在异质性。
这些结果表明,IGF-I浓度与EOC风险呈负相关,与组织学表型无关。未来的前瞻性研究应考虑这种关联的潜在机制,包括考虑IGF家族的其他成员,以更好地描述IGF信号在EOC病因学中的作用。