Publicaciones científicas
Genetically inferred birthweight, height, and puberty timing and risk of osteosarcoma
D Matthew Gianferante 1 , Amy Moore 1 , Logan G Spector 2 , William Wheeler 3 , Tianzhong Yang 4 , Aubrey Hubbard 1 , Richard Gorlick 5 , Ana Patiño-Garcia 6 , Fernando Lecanda 7 , Adrienne M Flanagan 8 , Fernanda Amary 9 , Irene L Andrulis 10 , Jay S Wunder 10 , David M Thomas 11 , Mandy L Ballinger 11 , Massimo Serra 12 , Claudia Hattinger 12 , Ellen Demerath 13 , Will Johnson 14 , Brenda M Birmann 15 , Immaculata De Vivo 16 , Graham Giles 17 , Lauren R Teras 18 , Alan Arslan 19 , Roel Vermeulen 20 , Jeannette Sample 2 , Neal D Freedman 1 , Wen-Yi Huang 1 , Stephen J Chanock 1 , Sharon A Savage 1 , Sonja I Berndt 1 , Lisa Mirabello 21
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.
CITA DEL ARTÍCULO Cancer Epidemiol. 2023 Aug 16;102432. doi: 10.1016/j.canep.2023.102432
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