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Genetic determinants of childhood and adult height associated with osteosarcoma risk.

Publication ,  Journal Article
Zhang, C; Morimoto, LM; de Smith, AJ; Hansen, HM; Gonzalez-Maya, J; Endicott, AA; Smirnov, IV; Metayer, C; Wei, Q; Eward, WC; Wiemels, JL; Walsh, KM
Published in: Cancer
September 15, 2018

BACKGROUND: Although increased height has been associated with osteosarcoma risk in previous epidemiologic studies, to the authors' knowledge the relative contribution of stature during different developmental timepoints remains unclear. Furthermore, the question of 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: The authors tested the associations between osteosarcoma risk and polygenic scores for adult height (416 variants), childhood height (6 variants), and birth length (5 variants) in 864 osteosarcoma cases 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 found to be associated with a 1.10-fold increase in the risk of osteosarcoma (95% confidence interval [95% CI], 1.01-1.19; P =.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 the risk of osteosarcoma (95% CI, 1.01-1.20; P =.023). The polygenic score for birth length was not found to be associated with osteosarcoma risk (P =.11). When adult and childhood height scores were modeled together, they were found to be independently associated with osteosarcoma risk (P =.037 and P = .043, respectively). An expression quantitative trait locus for cartilage intermediate layer protein 2 (CILP2), rs8103992, was significantly associated with osteosarcoma risk after adjustment for multiple comparisons (odds ratio, 1.35; 95% CI, 1.16-1.56 [P = 7.93×10-5 and Padjusted =.034]). CONCLUSIONS: A genetic propensity for taller adult and childhood height attainments contributed independently to osteosarcoma risk in the current study data. These results suggest that the biological pathways affecting normal bone growth may be involved in osteosarcoma etiology.

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Published In

Cancer

DOI

EISSN

1097-0142

Publication Date

September 15, 2018

Volume

124

Issue

18

Start / End Page

3742 / 3752

Location

United States

Related Subject Headings

  • Young Adult
  • White People
  • Risk Factors
  • Registries
  • Polymorphism, Single Nucleotide
  • Osteosarcoma
  • Oncology & Carcinogenesis
  • Neonatal Screening
  • Multifactorial Inheritance
  • Male
 

Citation

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ICMJE
MLA
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Zhang, C., Morimoto, L. M., de Smith, A. J., Hansen, H. M., Gonzalez-Maya, J., Endicott, A. A., … Walsh, K. M. (2018). Genetic determinants of childhood and adult height associated with osteosarcoma risk. Cancer, 124(18), 3742–3752. https://doi.org/10.1002/cncr.31645
Zhang, Chenan, Libby M. Morimoto, Adam J. de Smith, Helen M. Hansen, Julio Gonzalez-Maya, Alyson A. Endicott, Ivan V. Smirnov, et al. “Genetic determinants of childhood and adult height associated with osteosarcoma risk.Cancer 124, no. 18 (September 15, 2018): 3742–52. https://doi.org/10.1002/cncr.31645.
Zhang C, Morimoto LM, de Smith AJ, Hansen HM, Gonzalez-Maya J, Endicott AA, et al. Genetic determinants of childhood and adult height associated with osteosarcoma risk. Cancer. 2018 Sep 15;124(18):3742–52.
Zhang, Chenan, et al. “Genetic determinants of childhood and adult height associated with osteosarcoma risk.Cancer, vol. 124, no. 18, Sept. 2018, pp. 3742–52. Pubmed, doi:10.1002/cncr.31645.
Zhang C, Morimoto LM, de Smith AJ, Hansen HM, Gonzalez-Maya J, Endicott AA, Smirnov IV, Metayer C, Wei Q, Eward WC, Wiemels JL, Walsh KM. Genetic determinants of childhood and adult height associated with osteosarcoma risk. Cancer. 2018 Sep 15;124(18):3742–3752.
Journal cover image

Published In

Cancer

DOI

EISSN

1097-0142

Publication Date

September 15, 2018

Volume

124

Issue

18

Start / End Page

3742 / 3752

Location

United States

Related Subject Headings

  • Young Adult
  • White People
  • Risk Factors
  • Registries
  • Polymorphism, Single Nucleotide
  • Osteosarcoma
  • Oncology & Carcinogenesis
  • Neonatal Screening
  • Multifactorial Inheritance
  • Male