UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Genetically inferred birthweight, height, and puberty timing and risk of osteosarcoma

Gianferante, D Matthew; Moore, Amy; Spector, Logan G; Wheeler, William; Yang, Tianzhong; Hubbard, Aubrey; Gorlick, Richard; ... Mirabello, Lisa; + view all (2023) Genetically inferred birthweight, height, and puberty timing and risk of osteosarcoma. Cancer Epidemiology , Article 102432. 10.1016/j.canep.2023.102432. (In press). Green open access

[thumbnail of D. Matthew Gianferante_Cancer Epidemiology.pdf]
Preview
Text
D. Matthew Gianferante_Cancer Epidemiology.pdf - Accepted Version

Download (1MB) | Preview

Abstract

INTRODUCTION: Several studies have linked increased risk of osteosarcoma with tall stature, high birthweight, and early puberty, although evidence is inconsistent. We used genetic risk scores (GRS) based on established genetic loci for these traits and evaluated associations between genetically inferred birthweight, height, and puberty timing with osteosarcoma. METHODS: Using genotype data from two genome-wide association studies, totaling 1039 cases and 2923 controls of European ancestry, association analyses were conducted using logistic regression for each study and meta-analyzed to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses were conducted by case diagnosis age, metastasis status, tumor location, tumor histology, and presence of a known pathogenic variant in a cancer susceptibility gene. RESULTS: Genetically inferred higher birthweight was associated with an increased risk of osteosarcoma (OR =1.59, 95% CI 1.07-2.38, P = 0.02). This association was strongest in cases without metastatic disease (OR =2.46, 95% CI 1.44-4.19, P = 9.5 ×10-04). Although there was no overall association between osteosarcoma and genetically inferred taller stature (OR=1.06, 95% CI 0.96-1.17, P = 0.28), the GRS for taller stature was associated with an increased risk of osteosarcoma in 154 cases with a known pathogenic cancer susceptibility gene variant (OR=1.29, 95% CI 1.03-1.63, P = 0.03). There were no significant associations between the GRS for puberty timing and osteosarcoma. CONCLUSION: A genetic propensity to higher birthweight was associated with increased osteosarcoma risk, suggesting that shared genetic factors or biological pathways that affect birthweight may contribute to osteosarcoma pathogenesis.

Type: Article
Title: Genetically inferred birthweight, height, and puberty timing and risk of osteosarcoma
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.canep.2023.102432
Publisher version: https://doi.org/10.1016/j.canep.2023.102432
Language: English
Additional information: This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) License.
Keywords: Birthweight, Genetic risk score, Height, Osteosarcoma, Puberty timing
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology
URI: https://discovery.ucl.ac.uk/id/eprint/10181320
Downloads since deposit
20Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item