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

D. Matthew Gianferante, Amy Moore, Logan G. Spector, William Wheeler, Tianzhong Yang, Aubrey Hubbard, Richard Gorlick, Ana Patiño-Garcia, Fernando Lecanda, Adrienne M. Flanagan, Fernanda Amary, Irene L. Andrulis, Jay S. Wunder, David M. Thomas, Mandy L. Ballinger, Massimo Serra, Claudia Hattinger, Ellen Demerath, Will Johnson, Brenda M. BirmannImmaculata De Vivo, Graham Giles, Lauren R. Teras, Alan Arslan, Roel Vermeulen, Jeannette Sample, Neal D. Freedman, Wen Yi Huang, Stephen J. Chanock, Sharon A. Savage, Sonja I. Berndt, Lisa Mirabello

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number102432
JournalCancer Epidemiology
DOIs
StateAccepted/In press - 2023

Bibliographical note

Publisher Copyright:
© 2023

Keywords

  • Birthweight
  • Genetic risk score
  • Height
  • Osteosarcoma
  • Puberty timing

PubMed: MeSH publication types

  • Journal Article

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