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Association of CDH1 haplotypes with susceptibility to sporadic diffuse gastric cancer

Oncogene volume 21, pages 8192–8195 (2002)Cite this article

Abstract

Truncating mutations in the gene for the cell to cell adhesion protein E-cadherin are the most consistent genetic alterations observed in sporadic and hereditary diffuse gastric cancer (DGC). In addition to these inactivating mutations, a CDH1 promoter polymorphism at position −160 has been reported to lead to transcriptional downregulation of the gene in vitro. We therefore performed a case–control study to investigate whether this variant is associated with an increased susceptibility to DGC. The frequency of the −160A allele was significantly higher (P<0.005) in 53 diffuse gastric cancer cases compared to 70 matched controls. The odds ratio associated with the A-allele was 2.27 for CA-heterozygotes (95%CI 1.16–4.44) and 7.84 for AA-homozygotes (95%CI 2.89–21.24). Two additional polymorphisms (the 48+6T→C and the 2076C→T variant) were genotyped and shown to be equally distributed among cases and controls. Haplotype analysis with the three polymorphisms confirmed an association with disease (P<0.004). However, this analysis suggested the −160C→A CDH1 promoter polymorphism may be in linkage disequilibrium with a distinct aetiological locus or acts in combination with other functional variants in or near the CDH1 region.

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References

  • Avizienyte E, Launonen V, Salovaara R, Kiviluoto T, Aaltonen LA . 2001 J. Med. Genet. 38: 49–52

  • Berx G, Becker KF, Hofler H, van Roy F . 1998 Hum. Mutat. 12: 226–237

  • Borch K, Jonsson B, Tarpila E, Franzen T, Berglund J, Kullman E, Franzen L . 2000 Br. J. Surg. 87: 618–626

  • Dempster AP, Laird NM, Rubin DB . 1977 J. R. Stat. Soc. B 39: 1–38

  • Devlin B, Risch N . 1995 Genomics 29: 311–322

  • Dunbier A, Guilford P . 2001 Adv. Cancer Res. 83: 55–65

  • Fisher RA (ed). . 1951 The design of experiments London: Oliver and Boyd Ltd pp. 1–244

    Google Scholar 

  • Guilford P, Hopkins J, Harraway J, McLeod M, McLeod N, Harawira P, Taite H, Scoular R, Miller A, Reeve AE . 1998 Nature 392: 402–405

  • Howson CP, Hiyama T, Wynder EL . 1986 Epidemiol. Rev. 8: 1–27

  • Humar B, Toro TT, Graziano F, Muller H, Dobbie Z, Kwang-Yan H, Eng C, Hampel H, Gilbert D, Winship I, Parry S, Ward R, Findlay MP, Christian A, Tucker M, Tucker K, Merriman T, Guilford P . 2002 Hum. Mutat. 19: 518–525

  • Koeleman BP, Dudbridge F, Cordell HJ, Todd JA . 2000 Ann. Hum. Genet. 64: 207–213

  • Lauren P . 1965 Acta Pathol. Microbiol. Scand. 64: 31–49

  • Lauren PA, Nevalainen TJ . 1993 Cancer 71: 2926–2933

  • Lei H, Sjoberg-Margolin S, Salahshor S, Werelius B, Jandakova E, Hemminki K, Lindblom A, Vorechovsky I . 2002 Int. J. Cancer 98: 199–204

  • Li LC, Chui RM, Sasaki M, Nakajima K, Perinchery G, Au HC, Nojima D, Carroll P, Dahiya R . 2000 Cancer Res. 60: 873–876

  • Porter TR, Richards FM, Houlston RS, Evans DG, Jankowski JA, MacDonald F, Norbury G, Payne SJ, Fisher SA, Tomlinson I, Maher ER . 2002 Oncogene 21: 1928–1933

  • Risinger JI, Berchuck A, Kohler MF, Boyd J . 1994 Nat. Genet. 7: 98–102

  • Spielman RS, McGinnis RE, Ewens WJ . 1993 Am. J. Hum. Genet. 52: 506–516

  • Wu MS, Huang SP, Chang YT, Lin MT, Shun CT, Chang MC, Wang HP, Chen CJ, Lin JT . 2002 Cancer 94: 1443–1448

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Acknowledgements

We thank all the patients and volunteers who contributed to this study. We also thank Natalie J Kerr and Anita Dunbier for critical reading of the manuscript. B Humar was supported by a grant from the Swiss Cancer League (BIL SKL 993-02-2000) and the Swiss National Foundation.

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Authors and Affiliations

  1. Cancer Genetics Laboratory, University of Otago, Dunedin, Aotearoa, New Zealand

    Bostjan Humar, Tumi Toro, Tudor Burchill & Parry Guilford

  2. Division of Medical Oncology, Hospital of Urbino, Urbino, 61029, Italy

    Francesco Graziano

  3. Medical Oncology, Hospital of Parma, Parma, 43100, Italy

    Stefano Cascinu

  4. Medical Oncology, Hospital of Pesaro, Pesaro, 61100, Italy

    Vincenzo Catalano

  5. G Fornaini Institute of Biochemistry and Molecular Biology, University of Urbino, Urbino, 61029, Italy

    Anna M Ruzzo & Mauro Magnani

  6. Knowledge Engineering Laboratory, University of Otago, Dunedin, Aotearoa, New Zealand

    Matthias E Futschik

  7. Biochemistry Department, University of Otago, Dunedin, Aotearoa, New Zealand

    Tony Merriman

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  1. Bostjan Humar
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  2. Francesco Graziano
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  4. Vincenzo Catalano
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  7. Tumi Toro
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  10. Tony Merriman
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  11. Parry Guilford
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Correspondence to Parry Guilford.

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Humar, B., Graziano, F., Cascinu, S. et al. Association of CDH1 haplotypes with susceptibility to sporadic diffuse gastric cancer. Oncogene 21, 8192–8195 (2002). https://doi.org/10.1038/sj.onc.1205921

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