Germ-line genetic variation of TP53 in osteosarcoma

Sharon A. Savage, Laura Burdett, Rebecca Troisi, Chester Douglass, Robert N. Hoover, Stephen J. Chanock

Research output: Contribution to journalArticle

Abstract

Background. Osteosarcoma (OS) has been well described in individuals with germ-line TP53 mutations (Li-Fraumeni Syndrome) but typically occurs sporadically in adolescents and young adults. Single nucleotide polymorphisms (SNPs), the most common germ-line genetic variation, have been associated with risk for other types of cancer. We hypothesized that genetic variation in TP53 could be associated with OS risk based on its critical role in cell growth and effect of somatic mutations in OS tumors. Procedure. Twelve common SNPs in TP53 were genotyped in a case-control study of sporadic OS. These SNPs spanned the TP53 locus and captured common haplotypes. Genotype data were analyzed using contingency tables for additive, dominant, and recessive genetic models. PHASEv2.1 and HaploStats were used to evaluate haplotypes. Results. The recessive model suggested an increased risk of OS when two copies of TP53-34 C>G variant (IVS2+38, rs1 642785) were present, P - 0.041, odds ratio (OR) 6.70 (95% confidence interval [Cl] 1.06-41.6). The TP53-01 variant C>G (Pro72Arg, rs1042522) may also be associated with increased risk for OS, P = 0.028, OR 7.5 (95% Cl 1.20-46.3). Common TP53 haplotypes as well as the remaining 10 SNPs were not associated with risk for OS. Conclusions. These data do not indicate a strong link between variation in TP53 and OS risk, although they provide preliminary evidence of an increased risk of OS associated with variants at IVS2 - 38 and Pro72Arg. The findings warrant replication in further studies.

Original languageEnglish (US)
Pages (from-to)28-33
Number of pages6
JournalPediatric Blood and Cancer
Volume49
Issue number1
DOIs
StatePublished - Jul 2007
Externally publishedYes

Fingerprint

Osteosarcoma
Germ Cells
Single Nucleotide Polymorphism
Haplotypes
Li-Fraumeni Syndrome
Odds Ratio
Germ-Line Mutation
Genetic Models
Case-Control Studies
Young Adult
Genotype
Confidence Intervals
Mutation
Growth

Keywords

  • Genetic variation
  • Osteosarcoma
  • Single nucleotide polymorphism
  • TP53

ASJC Scopus subject areas

  • Cancer Research
  • Pediatrics, Perinatology, and Child Health
  • Hematology

Cite this

Savage, S. A., Burdett, L., Troisi, R., Douglass, C., Hoover, R. N., & Chanock, S. J. (2007). Germ-line genetic variation of TP53 in osteosarcoma. Pediatric Blood and Cancer, 49(1), 28-33. https://doi.org/10.1002/pbc.21077

Germ-line genetic variation of TP53 in osteosarcoma. / Savage, Sharon A.; Burdett, Laura; Troisi, Rebecca; Douglass, Chester; Hoover, Robert N.; Chanock, Stephen J.

In: Pediatric Blood and Cancer, Vol. 49, No. 1, 07.2007, p. 28-33.

Research output: Contribution to journalArticle

Savage, SA, Burdett, L, Troisi, R, Douglass, C, Hoover, RN & Chanock, SJ 2007, 'Germ-line genetic variation of TP53 in osteosarcoma', Pediatric Blood and Cancer, vol. 49, no. 1, pp. 28-33. https://doi.org/10.1002/pbc.21077
Savage SA, Burdett L, Troisi R, Douglass C, Hoover RN, Chanock SJ. Germ-line genetic variation of TP53 in osteosarcoma. Pediatric Blood and Cancer. 2007 Jul;49(1):28-33. https://doi.org/10.1002/pbc.21077
Savage, Sharon A. ; Burdett, Laura ; Troisi, Rebecca ; Douglass, Chester ; Hoover, Robert N. ; Chanock, Stephen J. / Germ-line genetic variation of TP53 in osteosarcoma. In: Pediatric Blood and Cancer. 2007 ; Vol. 49, No. 1. pp. 28-33.
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AB - Background. Osteosarcoma (OS) has been well described in individuals with germ-line TP53 mutations (Li-Fraumeni Syndrome) but typically occurs sporadically in adolescents and young adults. Single nucleotide polymorphisms (SNPs), the most common germ-line genetic variation, have been associated with risk for other types of cancer. We hypothesized that genetic variation in TP53 could be associated with OS risk based on its critical role in cell growth and effect of somatic mutations in OS tumors. Procedure. Twelve common SNPs in TP53 were genotyped in a case-control study of sporadic OS. These SNPs spanned the TP53 locus and captured common haplotypes. Genotype data were analyzed using contingency tables for additive, dominant, and recessive genetic models. PHASEv2.1 and HaploStats were used to evaluate haplotypes. Results. The recessive model suggested an increased risk of OS when two copies of TP53-34 C>G variant (IVS2+38, rs1 642785) were present, P - 0.041, odds ratio (OR) 6.70 (95% confidence interval [Cl] 1.06-41.6). The TP53-01 variant C>G (Pro72Arg, rs1042522) may also be associated with increased risk for OS, P = 0.028, OR 7.5 (95% Cl 1.20-46.3). Common TP53 haplotypes as well as the remaining 10 SNPs were not associated with risk for OS. Conclusions. These data do not indicate a strong link between variation in TP53 and OS risk, although they provide preliminary evidence of an increased risk of OS associated with variants at IVS2 - 38 and Pro72Arg. The findings warrant replication in further studies.

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