Relationship between height at diagnosis and bone tumours in young people: a meta-analysis

Arora, Ramandeep Singh; Kontopantelis, Evangelos; Alston, Richard; Eden, Tim; Geraci, Marco; Birch, Jillian M

doi:10.1007/s10552-011-9740-9

Cited by 29 publications

(21 citation statements)

References 48 publications

(64 reference statements)

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“…Aside from male sex, the factor most consistently associated with increased osteosarcoma risk is above-average height 1, 4, 15 . In 1967, Fraumeni observed that children with osteosarcoma were significantly taller at the time of diagnosis than a hospital-based control group and suggested that “the origin of at least some of these tumors is a function of skeletal growth rates during childhood and adolescence” 16 .…”

Section: Introductionmentioning

confidence: 99%

Genetic determinants of childhood and adult height associated with osteosarcoma risk

Zhang

Morimoto

Smith

et al. 2018

Cancer

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Background: Although increased height has been associated with osteosarcoma risk in previous epidemiologic studies, the relative contribution of stature during different developmental time-points remains unclear. Furthermore, how genetic determinants of height impact osteosarcoma etiology remains unexplored. Genetic variants associated with stature in previous genome-wide association studies may be biomarkers of osteosarcoma risk. Methods: We tested the associations between osteosarcoma risk and polygenic scores for adult height (416 variants), childhood height, (six variants), and birth length (five variants) in 864 osteosarcoma patients and 1879 controls of European ancestry. Results: Each standard deviation increase in the polygenic score for adult height, corresponding to a 1.7-cm increase in stature, was associated with a 1.10-fold increase in risk of osteosarcoma (95% CI: 1.01–1.19, P= 0.027). Each standard deviation increase in the polygenic score for childhood height, corresponding to a 0.5-cm increase in stature, was associated with a 1.10-fold increase in risk of osteosarcoma (95% CI: 1.01–1.20, P= 0.023). The polygenic score for birth length was not associated with osteosarcoma risk (P=0.11). When adult and childhood height scores were modeled together, they were independently associated with osteosarcoma risk (P=0.037 and 0.043, respectively). An eQTL for CILP2 (cartilage intermediate layer protein 2), rs8103992, was significantly associated with osteosarcoma risk after adjustment for multiple comparisons (OR=1.35, 95% CI: 1.16–1.56, P=7.93×10−5, Padjusted=0.034). Conclusions: Genetic propensity to taller adult and childhood height attainments contributed independently to osteosarcoma risk in our data. These results suggest that the biological pathways affecting normal bone growth may be involved in osteosarcoma etiology.

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Section: Introductionmentioning

confidence: 99%

Genetic determinants of childhood and adult height associated with osteosarcoma risk

Zhang

Morimoto

Smith

et al. 2018

Cancer

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“…Interestingly, large and giant dog breeds are more prone to develop osteosarcoma [15], which in dogs is biologically very similar to the human disease [16]. Two recent studies on human osteosarcoma suggest a positive correlation between patient birth-weight and height at diagnosis and the development of the disease [17,18]. Involvement of some members of IGF1R signaling in osteosarcoma has been described (as has been reviewed in Kolb et al .…”

Section: Introductionmentioning

confidence: 99%

IR/IGF1R signaling as potential target for treatment of high-grade osteosarcoma

et al. 2013

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BackgroundHigh-grade osteosarcoma is an aggressive tumor most often developing in the long bones of adolescents, with a second peak in the 5th decade of life. Better knowledge on cellular signaling in this tumor may identify new possibilities for targeted treatment.MethodsWe performed gene set analysis on previously published genome-wide gene expression data of osteosarcoma cell lines (n=19) and pretreatment biopsies (n=84). We characterized overexpression of the insulin-like growth factor receptor (IGF1R) signaling pathways in human osteosarcoma as compared with osteoblasts and with the hypothesized progenitor cells of osteosarcoma – mesenchymal stem cells. This pathway plays a key role in the growth and development of bone. Since most profound differences in mRNA expression were found at and upstream of the receptor of this pathway, we set out to inhibit IR/IGF1R using OSI-906, a dual inhibitor for IR/IGF1R, on four osteosarcoma cell lines. Inhibitory effects of this drug were measured by Western blotting and cell proliferation assays.ResultsOSI-906 had a strong inhibitory effect on proliferation of 3 of 4 osteosarcoma cell lines, with IC50s below 100 nM at 72 hrs of treatment. Phosphorylation of IRS-1, a direct downstream target of IGF1R signaling, was inhibited in the responsive osteosarcoma cell lines.ConclusionsThis study provides an in vitro rationale for using IR/IGF1R inhibitors in preclinical studies of osteosarcoma.

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“…3 Several studies showed that age, gender and height are risk factors for osteosarcoma. 4 The overall survival (OS) of osteosarcoma has been improved significantly because of effective chemotherapy combination. 5 Studies showed that complete surgical resection with an addition of chemotherapy has increased the 5-year OS to approximately 70%, 5 but improvements in osteosarcoma survival during the last decade have been limited.…”

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confidence: 99%

CXCR4‐mediated osteosarcoma growth and pulmonary metastasis is suppressed by MicroRNA‐613

et al. 2018

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Osteosarcoma is the most common primary bone malignancy. Recently, studies showed chemokine receptor 4 (CXCR4) played a critical role in osteosarcoma. However, the regulation of CXCR4 is not fully understood. microRNAs are short, non‐coding RNAs that play an important roles in post‐transcriptional regulation of gene expression in a variety of diseases including osteosarcoma. miR‐613 is a newly discovered miRNA and has been reported to function as a tumor suppressor in many cancers. In this study, we confirmed that both Stromal Cell‐Derived Factor (SDF‐1) and CXCR4 could be prognostic markers for osteosarcoma. Meanwhile this study found that SDF‐1/CXCR4 pathway regulated osteosarcoma cells proliferation, migration and reduced apoptosis. Besides, we demonstrated that miR‐613 was significantly downregulated in osteosarcoma patients. Elevated expression of miR‐613 directly suppressed CXCR4 expression and then decreased the proliferation, migration and induced apoptosis of osteosarcoma cells. Moreover, our study found that CXCR4 promoted the development of lung metastases and inhibition of CXCR4 by miR‐613 reduced lung metastases. These data indicated that CXCR4 mediated osteosarcoma cell growth and lung metastases and this effect can be suppressed by miR‐613 through directly downregulating CXCR4.

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Relationship between height at diagnosis and bone tumours in young people: a meta-analysis

Cited by 29 publications

References 48 publications

Genetic determinants of childhood and adult height associated with osteosarcoma risk

Genetic determinants of childhood and adult height associated with osteosarcoma risk

IR/IGF1R signaling as potential target for treatment of high-grade osteosarcoma

CXCR4‐mediated osteosarcoma growth and pulmonary metastasis is suppressed by MicroRNA‐613

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