BigTex
Well-Known Member
Abstract
The risk of growth hormone on cancer in adult with growth hormone deficiency remains unclear. We carried out a meta-analysis to evaluate the risk of cancer in adult with and without growth hormone replacement therapy. We searched PubMed, Web of Science, China National Knowledge Infrastructure, and WanFang databases up to 31 July 2016 for eligible studies. Pooled risk ratio (RR) with 95% confidence interval (CI) was calculated using fixed-or random-effects models if appropriate. The Newcastle-Ottawa Scale was used to assess the study quality. Two retrospective and seven prospective studies with a total of 11191 participants were included in the final analysis. The results from fixed-effects model showed this therapy was associated with the deceased risk of cancer in adult with growth hormone deficiency (RR=0.69, 95%CI: 0.59-0.82), with low heterogeneity within studies (I2=39.0%, P=0.108). We performed sensitivity analyses by sequentially omitting one study each time, and the pooled RRs did not materially change, indicating that our results were statistically stable. Begger's and Egger's tests suggested that there was no publication bias (Z=-0.63, P=0.520; t=0.16, P=0.874). Our study suggests that growth hormone replacement therapy could reduce risk of cancer in adult with growth hormone deficiency.Loading…
www.ncbi.nlm.nih.gov
DISCUSSION
Our results suggest that growth hormone replacement therapy reduces risk of cancer in adult. In addition, the association was also consistent in sensitivity analyses.The association between GH-IGF-1 and tumor shows a huge difference among vitro, animal experiments and epidemiological investigation. In vitro, growth hormone can stimulate lymphocytes to lymphoblast, growth hormone and its receptors were expressed in almost cancer cells. Over-expression of growth hormone could promote cell proliferation and apoptosis reduction for breast cancer. The IGF-1 also has proliferation and anti-apoptosis property for all types of cell. IGF-1 induces human leukemia cell proliferation and increased DNA replication of liver cell tumor in rat. This function can be inhibited using related antagonist inhibits [22]. Besides, IGF-1 in circulation can be combined with all kinds of binding protein, such as insulin-like growth factor binding protein 3 [23]. With different from IGF-1, insulin-like growth factor binding protein 3 can limit the bioactivity of IGF-1, and exerts its action of inhibiting tumor cell growth [24]. In animal experiments, selective knockout of IGF-1 gene causes reduction of IGF-1 level in circulation, and occurrence rate of breast cancer significantly decreased. Also, IGF-1 has a potential of promoting neoplasm metastasis [25]. Many epidemiology studies also mentioned IGF-1 level in plasma is associated with an increased risk of cancer [9, 10]. However, epidemiology studies did not found such an association in human investigation. All of studies included in the meta-analysis reported that growth hormone therapy is not associated with an increased risk of tumor occurrence or recurrence. Child et al found that the overall primary cancer risk in 6840 patients receiving growth hormones adults did not increase, but elevated standardized incidence were found for subgroups in the USA cohort defined by age <35 years [13]. Hartman conducted a prospective study with 1988 growth hormone-treated and 442 untreated GHD patients, and there was no evidence for a growth hormone therapy effect on cancer [17]. Buchfelder also found growth hormone substitution should not be withheld in deficient patients. But a period of 5 years may not have been long enough to verify this influence on recurrence potential [21]. In parallel with these above study, the latter study found unrelated results [12]. On the contrary, our results even found that growth hormone therapy is associated with a decreased risk of the whole group. This finding is the same as the Olsson and his colleagues' report that long-term (10 years) use of growth hormone in hypopituitarism may be considered to be safe in patients with residual pituitary adenomas [19]. Although we do not exactly how this results happen, the present findings hinted that growth hormone therapy are acceptable and safety under the evidence.
In conclusion, our results suggest that growth hormone replacement therapy reduces risk of cancer in adult with growth hormone deficiency. Future study with more long-term follow-up are needed to explore the association between GHRT and recurrence of cancer or other types of tumor.
