Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Short Report
  • Published:

CCND1 polymorphism and age of onset of hepatoblastoma

Oncogene volume 23, pages 4789–4792 (2004)Cite this article

Abstract

Cyclin D1, encoded by the gene CCND1, is a major regulator of the cell cycle transition from G1 phase to S phase. A CCND1 polymorphism (G to A) at codon 242, the boundary of exon 4 and intron 4, affects splicing such that exon 5 is not expressed in the A allele. Since exon 5 is involved in rapid turnover, the variant cyclin D1 corresponding to the A allele may have a longer half-life. A previous study demonstrated that in families with hereditary nonpolyposis colorectal cancer, the age of onset of colorectal cancer varied according to variation at this polymorphic site. We examined this CCND1polymorphism in a series hepatoblastoma, a childhood liver cancer that shares other molecular features with colon cancer. We determined in an analysis of 84 children with hepatoblastoma that the G/A exon 4 polymorphism in CCND1 is correlated with the age of onset of hepatoblastomas. The A/A genotype is associated with an earlier age of onset compared to the G/A or G/G genotype. The median age of patients with the G/G genotype was 22 months, compared to 17 months in patients with the G/A genotype and 11 months for the A/A genotype. These findings suggest that the CCND1 A polymorphism may contribute to tumor development in children with hepatoblastoma.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

Abbreviations

CCND1:

cyclin D1 gene

NSCLC:

non-small-cell lung cancer

LEF:

lymphoid-enhancing factor

PCR:

polymerase chain reaction

SSCP:

single-strand conformation polymorphisms

HNPCC:

hereditary nonpolyposis colon cancer

KW:

Kruskal–Wallis

OR:

odds ratio

CI:

95% confidence interval

References

  • Betticher DC, Thatcher N, Altermatt HJ, Hoban P, Ryder DJ and Heighway J . (1995). Oncogene, 11, 1005–1011.

  • Bulterys M, Goodman M, Smith M and Buckley J . (1999). Hepatic Tumors. Cancer Incidence and Survival Among Children and Adolescents: United States SEER Program 1975–1995, Ries L, Smigh M, Gurney J et al. (eds) NIH: Bethesda, MD.

    Google Scholar 

  • DeBaun MR and Tucker MA . (1998). J. Pediatr., 132, 398–400.

  • Donnellan R and Chetty R . (1998). J. Clin. Pathol.: Mol. Pathol., 51, 1–7.

  • Hollander M and Wolfe DE . (1999). Nonparametric Statistical Methods. John Wiley: New York.

    Google Scholar 

  • Hunter T and Pines J . (1994). Cell, 79, 573–582.

  • Jeng YM, Wu MZ, Moa TL, Chang MH and Hsu HC . (2000). Cancer Lett., 152, 45–51.

  • Koch A, Denkhaus D, Albrecht S, Leuschner I, von Schweinitz D and Pietsch T . (1999). Cancer Res., 59, 269–273.

  • Kong S, Amos CI, Luthra R, Lynch PM, Levin B and Frazier ML . (2000). Cancer Res., 60, 249–252.

  • Kong S, Wei Q, Christopher AI, Lynch PM, Levin B, Zong J and Frazier ML . (2001). J. Natl. Cancer Inst., 93, 1106–1108.

  • Kurahashi H, Takami K, Oue T, Kusafuka T, Okada A, Tawa A, Okada S and Nishisho I . (1995). Cancer Res., 55, 5007–5011.

  • Matthias C, Branigan K, Jahnke V, Leder K, Haas J, Heighway J, Jones PW, Strange RC, Fryer AA and Hoban PR . (1998). Clin. Cancer Res., 4, 2411–2418.

  • McKay JA, Douglas JJ, Ross VG, Curran S, Murray GI and Cassidy J . (2000). Int. J. Cancer, 88, 77–81.

  • Oda H, Imai Y, Nakatsuru Y, Hata J and Ishikawa T . (1996). Cancer Res., 56, 3320–3323.

  • Orita M, Iwahana H, Kanazawa H, Hayashi K and Sekiya T . (1989). Proc. Natl. Acad. Sci. USA, 86, 2766–2770.

  • Sawa H, Ohshima TA, Ukita H, Murakami H, Chiba Y, Kamada H, Hara M and Saito I . (1998). Oncogene, 16, 1701–1712.

  • Sherr CJ . (1996). Science, 274, 1672–1677.

  • Shtutman M, Zhurinsky J, Simcha I, Albanese C, D’Amico M, Pestell R and Ze'ev B . (1999). Proc. Natl. Acad. Sci. USA, 96, 5522–5527.

  • Takayasu H, Horie H, Hiyama E, Matsunaga T, Hayashi Y, Watanabe Y, Suita S, Kaneko M, Sasaki F, Hashizume K, Ozaki T, Furuuchi K, Tada M, Ohnuma N and Nakagawara A . (2001). Clin. Cancer Res., 7, 901–908.

Download references

Acknowledgements

This work was supported by the Children's Cancer Fund of Dallas, Texas Advanced Research Program grant # 010019-0105-2001, and NIH grant HL-53917. We acknowledge the help of Dr Jonathan Cohen in providing samples.

Author information

Author notes

  1. Samart Pakakasama

    Present address: Department of Pediatrics, Ramathibodi Hospital, Bangkok, Thailand

  2. Edwin C Douglass

    Present address: AstraZeneca Pharmaceuticals, Wilmington, DEL

Authors and Affiliations

  1. Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Samart Pakakasama & Gail E Tomlinson

  2. Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Samart Pakakasama, Tina T-L Chen, Carolyn Y Muller, Roger Lee & Gail E Tomlinson

  3. Academic Computer Services, University of Texas Southwestern Medical Center, Dallas, TX, USA

    William Frawley

  4. Department of Pediatrics, St. Christopher Hospital, Temple University, Philadelphia, PA, USA

    Edwin C Douglass

  5. Center for Epidemiology & Biostatistics, University of Texas Health Science Center at San Antonio,

    Brad H Pollock

  6. Department of Obstetrics-Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Carolyn Y Muller

Authors
  1. Samart Pakakasama
    View author publications

    Search author on:PubMed Google Scholar

  2. Tina T-L Chen
    View author publications

    Search author on:PubMed Google Scholar

  3. William Frawley
    View author publications

    Search author on:PubMed Google Scholar

  4. Carolyn Y Muller
    View author publications

    Search author on:PubMed Google Scholar

  5. Edwin C Douglass
    View author publications

    Search author on:PubMed Google Scholar

  6. Roger Lee
    View author publications

    Search author on:PubMed Google Scholar

  7. Brad H Pollock
    View author publications

    Search author on:PubMed Google Scholar

  8. Gail E Tomlinson
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Gail E Tomlinson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pakakasama, S., Chen, TL., Frawley, W. et al. CCND1 polymorphism and age of onset of hepatoblastoma. Oncogene 23, 4789–4792 (2004). https://doi.org/10.1038/sj.onc.1207499

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/sj.onc.1207499

Keywords

This article is cited by

Search

Advanced search

Quick links