Genetic determinants of childhood and adult height associated with osteosarcoma risk.
Abstract
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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https://hdl.handle.net/10161/18514Published Version (Please cite this version)
10.1002/cncr.31645Publication Info
Zhang, Chenan; Morimoto, Libby M; de Smith, Adam J; Hansen, Helen M; Gonzalez-Maya,
Julio; Endicott, Alyson A; ... Walsh, Kyle M (2018). Genetic determinants of childhood and adult height associated with osteosarcoma risk.
Cancer, 124(18). pp. 3742-3752. 10.1002/cncr.31645. Retrieved from https://hdl.handle.net/10161/18514.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
William Curtis Eward
Associate Professor of Orthopaedic Surgery
I am an Orthopaedic Oncologist, with dual clinical degrees (MD and DVM). I treat
complex sarcomas in people and animals. My laboratory studies comparative oncology
- discoveries we can make about cancer by analyses across different species.
Kyle Walsh
Associate Professor in Neurosurgery
Dr. Walsh is Associate Professor of Neurosurgery and Pathology, Director of the Division
of Neuro-epidemiology, and a Senior Fellow in the Duke Center for the Study of Aging
and Human Development. He leads Duke’s Neuro-epidemiology Lab, which integrates bench
science with statistical methods to study the neurobiology of glial senescence and
gliomagenesis. This research interrogates human genomic and epigenomic profiles to
identify both heritable and modifiable factors that contribute to ne
Qingyi Wei
Professor in Population Health Sciences
Qingyi Wei, MD, PhD, Professor in the Department of Medicine, is Associate Director
for Cancer Control and Population Sciences, Co-leader of CCPS and Co-leader of Epidemiology
and Population Genomics (Focus Area 1). He is a professor of Medicine and an internationally
recognized epidemiologist focused on the molecular and genetic epidemiology of head
and neck cancers, lung cancer, and melanoma. His research focuses on biomarkers and
genetic determinants for the DNA repair deficient phenotype and
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