Faculty of Medicine, University of Belgrade and Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center Belgrade, <br/>Dr Subotica 13, 11000 Belgrade, Serbia.
Eur J Endocrinol. 2013 Oct 1;169(5):R89-97. doi: 10.1530/EJE-13-0389. Print 2013 Nov.
It has been difficult to identify factors that affect the risk of cancer, but we know that people are at higher risk as they get older, or if they have a strong family history of cancer. The potential influence of environmental and behavioral factors remains poorly understood. Early population-based and case-control studies suggested that higher serum levels of IGF1 could be associated with increased cancer risk. Since GH therapy increases IGF1 levels, concern has been raised regarding its potential role as a cancer initiation factor. Experimental evidence and some clinical studies showed that when GH/IGF1 secretion or action was inhibited, a decreased incidence and rate of progression of cancers occurred. However, human populations comprise a garden variety of genotypes that respond differently to the same kind of exposures. Human population studies frequently reveal only very small effects to these exposures. So, are GH and cancer guilty by association? After more than 20 years, leukemia, a major safety issue initially believed associated with GH treatment in children with GH deficiency (GHD), has not been confirmed but the risk of second malignancies in patients previously treated with irradiation has been detected or confirmed through the National Cooperative Growth Study. Overall, this large study confirmed the favorable overall safety profile of GH therapy in children with GHD, and also highlighted specific populations at potential risk. The risk of secondary malignancy following radiotherapy is surely related to radiotherapy more than GH therapy that may increase growth but is less likely to start the oncogenic process. In GH-deficient adults treated with GH, observational studies (KIMS, HypoCCS) have shown that when IGF1 levels were targeted within normal age-related reference ranges, the occurrence of malignancies was not higher than in the general population.
确定影响癌症风险的因素一直很困难，但我们知道，随着年龄的增长，或者如果有强烈的家族癌症史，人们的风险更高。环境和行为因素的潜在影响仍知之甚少。早期的基于人群和病例对照研究表明，较高的血清 IGF1 水平可能与癌症风险增加有关。由于 GH 治疗会增加 IGF1 水平，因此人们担心它可能作为癌症起始因子发挥作用。实验证据和一些临床研究表明，当 GH/IGF1 分泌或作用受到抑制时，癌症的发生率和进展率会降低。然而，人类群体由对相同暴露表现出不同反应的各种基因型组成。人群研究经常仅对这些暴露显示出非常小的影响。那么，GH 和癌症是否有联系？20 多年后，最初被认为与儿童 GH 缺乏症（GHD）患者的 GH 治疗相关的白血病这一主要安全问题尚未得到证实，但通过国家合作生长研究发现或证实了以前接受过放疗的患者发生第二恶性肿瘤的风险。总体而言，这项大型研究证实了 GH 治疗 GHD 儿童的良好总体安全性，并强调了特定人群存在潜在风险。放疗后发生继发性恶性肿瘤的风险肯定与放疗有关，而与 GH 治疗有关，后者可能会增加生长，但不太可能引发致癌过程。在接受 GH 治疗的 GH 缺乏症成年患者中，观察性研究（KIMS、HypoCCS）表明，当 IGF1 水平在正常年龄相关参考范围内时，恶性肿瘤的发生并不高于一般人群。
