A Comprehensive Candidate Gene Approach Identifies Genetic Variation Associated with Osteosarcoma

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2011 May 31

PMID 21619704

Citations 42

Authors

Lisa Mirabello

Kai Yu

Sonja I Berndt

Laurie Burdett

Zhaoming Wang

Salma Chowdhury

Kedest Teshome

Arinze Uzoka

Amy Hutchinson

Tom Grotmol

Chester Douglass

Richard B Hayes

Robert N Hoover

Sharon A Savage

Affiliations

Soon will be listed here.

Abstract

Background: Osteosarcoma (OS) is a bone malignancy which occurs primarily in adolescents. Since it occurs during a period of rapid growth, genes important in bone formation and growth are plausible modifiers of risk. Genes involved in DNA repair and ribosomal function may contribute to OS pathogenesis, because they maintain the integrity of critical cellular processes. We evaluated these hypotheses in an OS association study of genes from growth/hormone, bone formation, DNA repair, and ribosomal pathways.

Methods: We evaluated 4836 tag-SNPs across 255 candidate genes in 96 OS cases and 1426 controls. Logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (CI).

Results: Twelve SNPs in growth or DNA repair genes were significantly associated with OS after Bonferroni correction. Four SNPs in the DNA repair gene FANCM (ORs 1.9-2.0, P = 0.003-0.004) and 2 SNPs downstream of the growth hormone gene GH1 (OR 1.6, P = 0.002; OR 0.5, P = 0.0009) were significantly associated with OS. One SNP in the region of each of the following genes was significant: MDM2, MPG, FGF2, FGFR3, GNRH2, and IGF1.

Conclusions: Our results suggest that several SNPs in biologically plausible pathways are associated with OS. Larger studies are required to confirm our findings.

Citing Articles

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References

Mirabello L, Pfeiffer R, Murphy G, Daw N, Patino-Garcia A, Troisi R . Height at diagnosis and birth-weight as risk factors for osteosarcoma. Cancer Causes Control. 2011; 22(6):899-908. PMC: 3494416. DOI: 10.1007/s10552-011-9763-2. View

Savage S, Burdett L, Troisi R, Douglass C, Hoover R, Chanock S . Germ-line genetic variation of TP53 in osteosarcoma. Pediatr Blood Cancer. 2006; 49(1):28-33. DOI: 10.1002/pbc.21077. View

Chauveinc L, Mosseri V, Quintana E, Desjardins L, Schlienger P, Doz F . Osteosarcoma following retinoblastoma: age at onset and latency period. Ophthalmic Genet. 2001; 22(2):77-88. DOI: 10.1076/opge.22.2.77.2228. View

Al-Romaih K, Bayani J, Vorobyova J, Karaskova J, Park P, Zielenska M . Chromosomal instability in osteosarcoma and its association with centrosome abnormalities. Cancer Genet Cytogenet. 2003; 144(2):91-9. DOI: 10.1016/s0165-4608(02)00929-9. View

Kappel C, Hirschfeld S, Helman L . Human osteosarcoma cell lines are dependent on insulin-like growth factor I for in vitro growth. Cancer Res. 1994; 54(10):2803-7. View

Sutter N, Bustamante C, Chase K, Gray M, Zhao K, Zhu L . A single IGF1 allele is a major determinant of small size in dogs. Science. 2007; 316(5821):112-5. PMC: 2789551. DOI: 10.1126/science.1137045. View

Hoeijmakers J . DNA damage, aging, and cancer. N Engl J Med. 2009; 361(15):1475-85. DOI: 10.1056/NEJMra0804615. View

Koshkina N, Kleinerman E, Li G, Zhao C, Wei Q, Sturgis E . Exploratory analysis of Fas gene polymorphisms in pediatric osteosarcoma patients. J Pediatr Hematol Oncol. 2007; 29(12):815-21. DOI: 10.1097/MPH.0b013e3181581506. View

Rytting M, Pearson P, Raymond A, Ayala A, Murray J, Yasko A . Osteosarcoma in preadolescent patients. Clin Orthop Relat Res. 2000; (373):39-50. DOI: 10.1097/00003086-200004000-00007. View

10.

Mirabello L, Troisi R, Savage S . International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons. Int J Cancer. 2009; 125(1):229-34. PMC: 3048853. DOI: 10.1002/ijc.24320. View

11.

Sandberg A, Bridge J . Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: osteosarcoma and related tumors. Cancer Genet Cytogenet. 2003; 145(1):1-30. View

12.

Miller R . Contrasting epidemiology of childhood osteosarcoma, Ewing's tumor, and rhabdomyosarcoma. Natl Cancer Inst Monogr. 1981; (56):9-15. View

13.

Meetei A, Medhurst A, Ling C, Xue Y, Singh T, Bier P . A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M. Nat Genet. 2005; 37(9):958-63. PMC: 2704909. DOI: 10.1038/ng1626. View

14.

Pollak M, Sem A, Richard M, Tetenes E, Bell R . Inhibition of metastatic behavior of murine osteosarcoma by hypophysectomy. J Natl Cancer Inst. 1992; 84(12):966-71. DOI: 10.1093/jnci/84.12.966. View

15.

Hansen M, Seton M, Merchant A . Osteosarcoma in Paget's disease of bone. J Bone Miner Res. 2007; 21 Suppl 2:P58-63. DOI: 10.1359/jbmr.06s211. View

16.

Modesto C . Analysis of the human tumour necrosis factor-alpha (TNFalpha) gene promoter polymorphisms in children with bone cancer. J Med Genet. 2001; 37(10):789-92. PMC: 1757156. DOI: 10.1136/jmg.37.10.789. View

17.

Lindor N, McMaster M, Lindor C, Greene M . Concise handbook of familial cancer susceptibility syndromes - second edition. J Natl Cancer Inst Monogr. 2008; (38):1-93. DOI: 10.1093/jncimonographs/lgn001. View

18.

Gelberg K, Fitzgerald E, Hwang S, Dubrow R . Growth and development and other risk factors for osteosarcoma in children and young adults. Int J Epidemiol. 1997; 26(2):272-8. DOI: 10.1093/ije/26.2.272. View

19.

Shimamura A, Alter B . Pathophysiology and management of inherited bone marrow failure syndromes. Blood Rev. 2010; 24(3):101-22. PMC: 3733544. DOI: 10.1016/j.blre.2010.03.002. View

20.

Mirabello L, Troisi R, Savage S . Osteosarcoma incidence and survival rates from 1973 to 2004: data from the Surveillance, Epidemiology, and End Results Program. Cancer. 2009; 115(7):1531-43. PMC: 2813207. DOI: 10.1002/cncr.24121. View