Skip to main content
SpringerLink
Log in

Association ofp53 codon arg72pro andp73 G4C14-to-A4T14 at exon 2 genetic polymorphisms with the risk of japanese breast cancer

  • Original Article
  • Published:
Breast Cancer Aims and scope Submit manuscript

Abstract

Background

The association between breast cancer risk and genetic polymorphisms ofp53 at codon 72 (Arg72Pro) has been investigated by several studies, but the results are not consistent. The aim of this case-control study conducted in Nagoya, Japan, was to reconfirm the results of prior studies of polymorphisms ofp53 Arg72Pro, and to test if polymorphisms ofp73 G4C14-to-A4T14 at exon 2 (G4A) were also associated with breast cancer risk.

Methods

The cases were 200 breast cancer patients who visited Aichi Cancer Center Hospital. The controls were 282 local citizens who underwent a health check-up. All cases and controls were recruited from Chubu Japan. Genotyping was carried out by Polymerase chain reaction with confronting two-pair primers.

Results

Thep53 genotype distribution was 40.4% forArg72 homozygous, 48.9% for heterozygous, and 10.7% forPro72 homozygous in controls, and 32.0%, 50.0%, and 18.0% in cases, respectively. A comparison between cases and controls indicated a significantly increased risk forPro72 homozygosity in cases (odds ratio = 2.14; 95% confidence interval = 1.21-3.79). The genotypic frequencies forp73 G4A were 54.3% forGIG, 39.7% forG/A, and 6.0% forAI A in controls; and 59.0%, 32.0%, and 9.0% in cases, respectively. There were no significant differences inp73 G4A frequency between cases and controls.

Conclusions

This study implies an association of breast cancer risk with thep53 polymorphismArg72Pro, but not withp 73 G4A.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

ACCH:

Aichi Cancer Center Hospital

Arg:

Arginine

Arg72Pro:

Arginine/proline (Arg/Pro) polymorphism at codon 72

CI:

Confidence interval

G4A:

A dinucleotide polymorphism at positions 4 and 14 of exon 2 inp73 gene

OR:

Odds ratio

PCR-CTPP:

Polymerase chain reaction with confronting two-pair primers

Pro:

Proline

References

  1. Willett W: The search for the causes of breast and colon cancer.Nature 338:389–394, 1989.

    Article  PubMed  CAS  Google Scholar 

  2. Buell P: Changing incidence of breast cancer in Japanese-American women.J Natl Cancer Inst 51:1479–1483, 1973.

    PubMed  CAS  Google Scholar 

  3. Hirose K, Tajima K, Hamajima N, Kuroishi T, Miura S, Tokudome S: Impact of family history on the risk of breast cancer among the Japanese.Jpn J Cancer Res 88:1130–1136, 1997.

    PubMed  CAS  Google Scholar 

  4. Mucci LA, Wedren S, Tamimi RM, Trichopoulos D, Adami HO: The role of gene-environment interaction in the aetiology of human cancer: examples from cancers of the large bowel, lung and breast.J Intern Med 249:477–493, 2001.

    Article  PubMed  CAS  Google Scholar 

  5. Crook T, Crossland S, Crompton MR, Osin P, Guster-son BA: p53 mutations in BRCA1-associated familial breast cancer.Lancet 350:638–639, 1997.

    Article  PubMed  CAS  Google Scholar 

  6. Levine AJ: p53, the cellular gatekeeper for growth and division.Cell 88:323–331, 1997.

    Article  PubMed  CAS  Google Scholar 

  7. Schmale H, Bamberger C: A novel protein with strong homology to the tumor suppressor p53.Oncogene 15:1363–1367, 1997.

    Article  PubMed  CAS  Google Scholar 

  8. Kaelin WG: The emerging p53 gene family.J Natl Cancer Inst 91:594–598, 1999.

    Article  PubMed  CAS  Google Scholar 

  9. Kaghad M, Bonnet H, Yang A, Creancier L, Biscan JC, Valent A, Minty A, Chalon P, Lelias JM, Dumont X, Ferrara P, McKeon F, Caput D: Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers.Cell 90:809–819, 1997.

    Article  PubMed  CAS  Google Scholar 

  10. Jost CA, Marin MC, Kaelin WG: p73 is a simian [correction of human] p53-related protein that can induce apoptosis.Nature 389:191–194, 1997.

    Article  PubMed  CAS  Google Scholar 

  11. Marin MC, Jost CA, Brooks LA, Irwin MS, O’Nions J, Tidy JA, James N, McGregor JM, Harwood CA, Yulug IG, Vousden KH, Allday MJ, Gusterson B, Ikawa S, Hinds PW, Crook T, Kaelin WG Jr: A common polymorphism acts as an intragenic modifier of mutant p53 behavior.Nat Genet 25:47–54, 2000.

    Article  PubMed  CAS  Google Scholar 

  12. Storey A, Thomas M, Kalita A, Harwood C, Gardiol D, Mantovani F, Breuer J, Leigh IM, Matlashewski G, Banks L: Role of a p53 polymorphism in the development of human papillomavirus associated cancer.Nature 393:229–234, 1998.

    Article  PubMed  CAS  Google Scholar 

  13. Kawajiri K, Nakachi K, Imai K, Watanabe J, Hayashi S: Germ line polymorphisms of p53 and CYP1A1 genes involved in human lung cancer.Carcinogenesis 14:1085–1089, 1993.

    Article  PubMed  CAS  Google Scholar 

  14. Buller RE, Sood A, Fullenkamp C, Sorosky J, Powills K, Anderson B: The influence of the p53 codon 72 polymorphism on ovarian carcinogenesis and prognosis.Cancer Gene Ther 4:239–245, 1997.

    PubMed  CAS  Google Scholar 

  15. Wang YC, Chen CY, Chen SK, Chang YY, Lin P: p53 codon 72 polymorphism in Taiwanese lung cancer patients: association with lung cancer susceptibility and prognosis.Clin Cancer Res 5:129–134, 1999.

    PubMed  CAS  Google Scholar 

  16. Rosenthal AN, Ryan A, Al-Jehani RM, Storey A, Harwood CA, Jacobs IJ: p53 codon 72 polymorphism and risk of cervical cancer in UK.Lancet 352:871–872, 1998.

    Article  PubMed  CAS  Google Scholar 

  17. Minaguchi T, Kanamori Y, Matsushima M, Yoshikawa H, Taketani Y, Nakamura Y: No evidence of correlation between polymorphism at codon 72 of p53 and risk of cervical cancer in Japanese patients with Papillomavirus 16/18 infection.Cancer Res 58:4585–4586, 1998.

    PubMed  CAS  Google Scholar 

  18. Klaes R, Ridder R, Schaefer U, Benner A, von Knebel Doeberitz M: No evidence of p53 allele-specific predisposition in human papillomavirus-associated cervical cancer.J Mol Med 77:299–302, 1999.

    Article  PubMed  CAS  Google Scholar 

  19. Giannoudis A, Graham DA, Southern SA, Herrington CS: p53 codon 72 ARG/PRO polymorphism is not related to HPV type or lesion grade in low- and highgrade squamous intra-epithelial lesions and invasive squamous carcinoma of the cervix.Int J Cancer 83:66–69, 1999.

    Article  PubMed  CAS  Google Scholar 

  20. Sjalander A, Birgander R, Hallmans G, Cajander S, Lenner P, Athlin L, Beckman G, Beckman L: p53 polymorphisms and haplotypes in breast cancer.Carcinogenesis 17:1313–1316, 1996.

    Article  PubMed  CAS  Google Scholar 

  21. Hamajima N, Matsuo K, Suzuki T, Nakamura T, Matsuura A, Hatooka S, Shinoda M, Kodera Y, Yamamura Y, Hirai T, Kato T, Tajima K: No association of p73 G4C14-to-A4T14 at exon 2 and p53 codon Arg72Pro polymorphisms with the risk of digestive tract cancers in Japanese.Cancer Lett 181:81–85, 2002.

    Article  PubMed  CAS  Google Scholar 

  22. Ryan BM, McManus R, Daly JS, Carton E, Keeling PW, Reynolds JV, Kelleher D: A common p73 polymorphism is associated with a reduced incidence of oesophageal carcinoma.Br J Cancer 85:1499–1503, 2001.

    Article  PubMed  CAS  Google Scholar 

  23. Hamajima N, Iwata H, Obata Y, Matsuo K, Mizutani M, Iwase T, Miura S, Okuma K, Ohashi K, Tajima K: No association of the 5’promoter region polymorphism of CYP17 with breast cancer risk in Japan.Jpn J Cancer Res 91:880–885, 2000.

    PubMed  CAS  Google Scholar 

  24. Huang XE, Hamajima N, Saito T, Matsuo K, Mizutani M, Iwata H, Iwase T, Miura S, Mizuno T, Tokudome S, Tajima K: Possible association of ß2 and ß3 adrenergic receptor gene polymorphisms with susceptibility to breast cancer.Breast Cancer Res 3:246–269, 2001.

    Article  Google Scholar 

  25. Hamajima N, Saito T, Matsuo K, Kozaki K, Takahashi T, Tajima K: Polymerase chain reaction with confronting two-pair primers for polymorphism genotyping.Jpn J Cancer Res 91:865–868, 2000.

    PubMed  CAS  Google Scholar 

  26. SAS Institute. “SAS/STAT user’s guide,” Ver. 6, 4th Ed. SAS Institute Inc., Cary, NC, pp1071–1126, 1990.

    Google Scholar 

  27. Stata Corp. “Stata Statistical Software” Release 6. Stata Corporation. College Station, TX, 1999.

    Google Scholar 

  28. Papadakis EN, Dokianakis DN, Spandidos DA: p53 codon 72 polymorphism as a risk factor in the development of breast cancer.Mol Cell Biol Res Commun 3:389–392, 2000.

    Article  PubMed  CAS  Google Scholar 

  29. Wang-Gohrke S, Rebbeck TR, Besenfelder W, Kreienberg R, Runnebaum IB: p53 germline polymorphisms are associated with an increased risk for breast cancer in German women.Anticancer Res 18:2095–2099, 1998.

    PubMed  CAS  Google Scholar 

  30. London SJ, Daly AK, Thomas DC, Caporaso NE, Idle JR: Methodological issues in the interpretation of studies of the CYP2D6 genotype in relation to lung cancer risk.Pharmacogenetics 4:107–108, 1994.

    Article  PubMed  CAS  Google Scholar 

  31. Matlashewski GJ, Tuck S, Pim D,et al: Primary structure polymorphism at amino acid residue 72 of human p53.Mol Cell Biol 7:961–963, 1987.

    PubMed  CAS  Google Scholar 

  32. Thomas M, Kalita A, Labrecque S, Pim D, Banks L, Matlashewski G: Two polymorphic variants of wildtype p53 differ biochemically and biologically.Mol Cell Biol 19:1092–1100, 1999.

    PubMed  CAS  Google Scholar 

  33. Hamajima N, Matsuo K, Yuasa H: Adjustment of prognostic effects in prevalent case-control studies on genotype.J Epidemiol 11:204–210, 2001.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Health Promotion and Preventive Medicine, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-ku, 467-8601, Nagoya, Japan

    Xin-En Huang, Jin Xiang & Shinkan Tokudome

  2. Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nanjing, People’s Republic or China

    Xin-En Huang, Nobuyuki Hamajima, Keitaro Matsuo, Kaoru Hirose & Kazuo Tajima

  3. Department of Health Nagoya Municipal Government, Jiangsu Cancer Hospital and Research Institute, Nanjing, People’s Republic or China

    Nobuyuki Katsuda

  4. Department of Breast Surgery, Aichi Cancer Center Hospital, Japan

    Mitsuhiro Mizutani, Hiroji Iwata & Shigeto Miura

  5. Department of Medical Oncology, Jiangsu Cancer Hospital and Research Institute, Nanjing, People’s Republic or China

    Xin-En Huang

Authors
  1. Xin-En Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nobuyuki Hamajima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nobuyuki Katsuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Keitaro Matsuo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kaoru Hirose
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mitsuhiro Mizutani
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hiroji Iwata
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Shigeto Miura
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jin Xiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Shinkan Tokudome
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Kazuo Tajima
    View author publications

    You can also search for this author in PubMed Google Scholar

About this article

Cite this article

Huang, XE., Hamajima, N., Katsuda, N. et al. Association ofp53 codon arg72pro andp73 G4C14-to-A4T14 at exon 2 genetic polymorphisms with the risk of japanese breast cancer. Breast Cancer 10, 307–311 (2003). https://doi.org/10.1007/BF02967650

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02967650

Key words

Search

Navigation