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. Birmann; Immaculata 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

doi:10.1016/j.canep.2023.102432

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

Pediatrics

Research output: Contribution to journal › Article › peer-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 language	English (US)
Article number	102432
Journal	Cancer Epidemiology
DOIs	https://doi.org/10.1016/j.canep.2023.102432
State	Accepted/In press - 2023

Keywords

Birthweight
Genetic risk score
Height
Osteosarcoma
Puberty timing

ASJC Scopus subject areas

Epidemiology
Oncology
Cancer Research

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10.1016/j.canep.2023.102432

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Gianferante, D. M., Moore, A., Spector, L. G., Wheeler, W., Yang, T., Hubbard, A., Gorlick, R., Patiño-Garcia, A., Lecanda, F., Flanagan, A. M., Amary, F., Andrulis, I. L., Wunder, J. S., Thomas, D. M., Ballinger, M. L., Serra, M., Hattinger, C., Demerath, E., Johnson, W., ... Mirabello, L. (Accepted/In press). Genetically inferred birthweight, height, and puberty timing and risk of osteosarcoma. Cancer Epidemiology, Article 102432. https://doi.org/10.1016/j.canep.2023.102432

Gianferante, DM, Moore, A, Spector, LG, Wheeler, W, Yang, T, Hubbard, A, Gorlick, R, Patiño-Garcia, A, Lecanda, F, Flanagan, AM, Amary, F, Andrulis, IL, Wunder, JS, Thomas, DM, Ballinger, ML, Serra, M, Hattinger, C, Demerath, E, Johnson, W, Birmann, BM, De Vivo, I, Giles, G, Teras, LR, Arslan, A, Vermeulen, R, Sample, J, Freedman, ND, Huang, WY, Chanock, SJ, Savage, SA, Berndt, SI & Mirabello, L 2023, 'Genetically inferred birthweight, height, and puberty timing and risk of osteosarcoma', Cancer Epidemiology. https://doi.org/10.1016/j.canep.2023.102432

@article{13da45dabc4c44c0a4534ce3489c2d1d,

title = "Genetically inferred birthweight, height, and puberty timing and risk of osteosarcoma",

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.",

keywords = "Birthweight, Genetic risk score, Height, Osteosarcoma, Puberty timing",

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

note = "Publisher Copyright: {\textcopyright} 2023",

year = "2023",

doi = "10.1016/j.canep.2023.102432",

language = "English (US)",

journal = "Cancer Epidemiology",

issn = "1877-7821",

publisher = "Elsevier BV",

}

TY - JOUR

T1 - Genetically inferred birthweight, height, and puberty timing and risk of osteosarcoma

AU - Gianferante, D. Matthew

AU - Moore, Amy

AU - Spector, Logan G.

AU - Wheeler, William

AU - Yang, Tianzhong

AU - Hubbard, Aubrey

AU - Gorlick, Richard

AU - Patiño-Garcia, Ana

AU - Lecanda, Fernando

AU - Flanagan, Adrienne M.

AU - Amary, Fernanda

AU - Andrulis, Irene L.

AU - Wunder, Jay S.

AU - Thomas, David M.

AU - Ballinger, Mandy L.

AU - Serra, Massimo

AU - Hattinger, Claudia

AU - Demerath, Ellen

AU - Johnson, Will

AU - Birmann, Brenda M.

AU - De Vivo, Immaculata

AU - Giles, Graham

AU - Teras, Lauren R.

AU - Arslan, Alan

AU - Vermeulen, Roel

AU - Sample, Jeannette

AU - Freedman, Neal D.

AU - Huang, Wen Yi

AU - Chanock, Stephen J.

AU - Savage, Sharon A.

AU - Berndt, Sonja I.

AU - Mirabello, Lisa

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Birthweight

KW - Genetic risk score

KW - Height

KW - Osteosarcoma

KW - Puberty timing

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U2 - 10.1016/j.canep.2023.102432

DO - 10.1016/j.canep.2023.102432

M3 - Article

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AN - SCOPUS:85168488429

SN - 1877-7821

JO - Cancer Epidemiology

JF - Cancer Epidemiology

M1 - 102432

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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