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Breast Cancer Genomics Based on Biobanks

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Methods in Biobanking

Part of the book series: Methods in Molecular Biology ((MIMB,volume 675))

Abstract

Attempts to find genes contribution to complex diseases, such as cancer, require new study designs which incorporate an efficient use of population resources and modern genotyping technologies. We describe here two approaches, used by us for the study of breast cancer, both of which take the use of biobanks. One uses a cancer registry as a source of case information, which is then linked to a biobank on blood DNA. The biobank provides also samples from matched controls. After genotyping, clinical data are retrieved from hospital records, and the results can be presented for genotype-specific cancer risks, or similarly for genotype-specific clinical and survival parameters. The second approach uses registered data on cancer in families or among twins. On defined groups of patients, paraffin tissue is collected by contacting the pathology departments of the hospitals where the patients were diagnosed. Tumor and healthy tissue is prepared and used for mutation, the loss of heterozygosity, or copy number analysis. We believe that in the era of whole-genome genotyping technologies, the importance of well-characterized sample sets cannot be overemphasized. Samples rather than technologies limit the rate of gene discovery in complex diseases.

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References

  1. Syrjakoski, K., Vahteristo, P., Eerola, H., Tamminen, A., Kivinummi, K., Sarantaus, L., Holli, K., Blomqvist, C., Kallioniemi, O.P., Kainu, T. and Nevanlinna, H. (2000) Population-based study of BRCA1 and BRCA2 mutations in 1035 unselected Finnish breast cancer patients. J Natl Cancer Inst, 92, 1529–1531.

    Article  PubMed  CAS  Google Scholar 

  2. Risch, H.A., McLaughlin, J.R., Cole, D.E., Rosen, B., Bradley, L., Kwan, E., Jack, E., Vesprini, D.J., Kuperstein, G., Abrahamson, J.L., Fan, I., Wong, B. and Narod, S.A. (2001) Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet, 68, 700–710.

    Article  PubMed  CAS  Google Scholar 

  3. Lynch, H.T. and de la Chapelle, A. (2003) Hereditary colorectal cancer. N Engl J Med, 348, 919–932.

    Article  PubMed  CAS  Google Scholar 

  4. Lichtenstein, P., Holm, N.V., Verkasalo, P.K., Iliadou, A., Kaprio, J., Koskenvuo, M., Pukkala, E., Skytthe, A. and Hemminki, K. (2000) Environmental and heritable factors in the causation of cancer – analyses of cohorts of twins from Sweden, Denmark, and Finland [see comments]. N Engl J Med, 343, 78–85.

    Article  PubMed  CAS  Google Scholar 

  5. Hemminki, K., Lorenzo Bermejo, J. and Forsti, A. (2006) The balance between heritable and environmental aetiology of human disease. Nat Rev Genet, 7, 958–965.

    Article  PubMed  CAS  Google Scholar 

  6. Buchanan, A.V., Weiss, K.M. and Fullerton, S.M. (2006) Dissecting complex disease: the quest for the Philosopher’s Stone? Int J Epidemiol, 35, 562–571.

    Article  PubMed  Google Scholar 

  7. Wang, W.Y., Barratt, B.J., Clayton, D.G. and Todd, J.A. (2005) Genome-wide association studies: theoretical and practical concerns. Nat Rev Genet, 6, 109–118.

    Article  PubMed  CAS  Google Scholar 

  8. Forsti, A., Jin, Q., Altieri, A., Johansson, R., Wagner, K., Enquist, K., Grzybowska, E., Pamula, J., Pekala, W., Hallmans, G., Lenner, P. and Hemminki, K. (2007) Polymorphisms in the KDR and POSTN genes: association with breast cancer susceptibility and prognosis. Breast Cancer Res Treat, 101, 83–93.

    Article  PubMed  Google Scholar 

  9. Jin, Q., Hemminki, K., Enquist, K., Lenner, P., Grzybowska, E., Klaes, R., Henriksson, R., Chen, B., Pamula, J., Pekala, W., Zientek, H., Rogozinska-Szczepka, J., Utracka-Hutka, B., Hallmans, G. and Forsti, A. (2005) Vascular endothelial growth factor polymorphisms in relation to breast cancer development and prognosis. Clin Cancer Res, 11, 3647–3653.

    Article  PubMed  CAS  Google Scholar 

  10. Lei, H., Hemminki, K., Altieri, A., Johansson, R., Enquist, K., Hallmans, G., Lenner, P. and Forsti, A. (2006) Promoter polymorphisms in matrix metalloproteinases and their inhibitors: few associations with breast cancer susceptibility and progression. Breast Cancer Res Treat, 103(1), 61–69.

    Article  PubMed  Google Scholar 

  11. Kaaks, R., Lundin, E., Rinaldi, S., Manjer, J., Biessy, C., Soderberg, S., Lenner, P., Janzon, L., Riboli, E., Berglund, G. and Hallmans, G. (2002) Prospective study of IGF-I, IGF-binding proteins, and breast cancer risk, in northern and southern Sweden. Cancer Causes Control, 13, 307–316.

    Article  PubMed  Google Scholar 

  12. Ferrara, N., Gerber, H.P. and LeCouter, J. (2003) The biology of VEGF and its receptors. Nat Med, 9, 669–676.

    Article  PubMed  CAS  Google Scholar 

  13. Morabito, A., Sarmiento, R., Bonginelli, P. and Gasparini, G. (2004) Antiangiogenic strategies, compounds, and early clinical results in breast cancer. Crit Rev Oncol Hematol, 49, 91–107.

    Article  PubMed  Google Scholar 

  14. Kranz, A., Mattfeldt, T. and Waltenberger, J. (1999) Molecular mediators of tumor angiogenesis: enhanced expression and activation of vascular endothelial growth factor receptor KDR in primary breast cancer. Int J Cancer, 84, 293–298.

    Article  PubMed  CAS  Google Scholar 

  15. Nakopoulou, L., Stefanaki, K., Panayotopoulou, E., Giannopoulou, I., Athanassiadou, P., Gakiopoulou-Givalou, H. and Louvrou, A. (2002) Expression of the vascular endothelial growth factor receptor-2/Flk-1 in breast carcinomas: correlation with proliferation. Hum Pathol, 33, 863–870.

    Article  PubMed  CAS  Google Scholar 

  16. Ryden, L., Linderholm, B., Nielsen, N.H., Emdin, S., Jonsson, P.E. and Landberg, G. (2003) Tumor specific VEGF-A and VEGFR2/KDR protein are co-expressed in breast cancer. Breast Cancer Res Treat, 82, 147–154.

    Article  PubMed  CAS  Google Scholar 

  17. Shao, R., Bao, S., Bai, X., Blanchette, C., Anderson, R.M., Dang, T., Gishizky, M.L., Marks, J.R. and Wang, X.F. (2004) Acquired expression of periostin by human breast cancers promotes tumor angiogenesis through up-regulation of vascular endothelial growth factor receptor 2 expression. Mol Cell Biol, 24, 3992–4003.

    Article  PubMed  CAS  Google Scholar 

  18. Sasaki, H., Yu, C.Y., Dai, M., Tam, C., Loda, M., Auclair, D., Chen, L.B. and Elias, A. (2003) Elevated serum periostin levels in patients with bone metastases from breast but not lung cancer. Breast Cancer Res Treat, 77, 245–252.

    Article  PubMed  CAS  Google Scholar 

  19. Awata, T., Inoue, K., Kurihara, S., Ohkubo, T., Watanabe, M., Inukai, K., Inoue, I. and Katayama, S. (2002) A common polymorphism in the 5′-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes. Diabetes, 51, 1635–1639.

    Article  PubMed  CAS  Google Scholar 

  20. Shahbazi, M., Fryer, A.A., Pravica, V., Brogan, I.J., Ramsay, H.M., Hutchinson, I.V. and Harden, P.N. (2002) Vascular endothelial growth factor gene polymorphisms are associated with acute renal allograft rejection. J Am Soc Nephrol, 13, 260–264.

    PubMed  CAS  Google Scholar 

  21. Crawford, H.C. and Matrisian, L.M. (1994) Tumor and stromal expression of matrix metalloproteinases and their role in tumor progression. Invasion Metastasis, 14, 234–245.

    PubMed  CAS  Google Scholar 

  22. Lambert, E., Dasse, E., Haye, B. and Petitfrere, E. (2004) TIMPs as multifacial proteins. Crit Rev Oncol Hematol, 49, 187–198.

    Article  PubMed  Google Scholar 

  23. Noda, M., Oh, J., Takahashi, R., Kondo, S., Kitayama, H. and Takahashi, C. (2003) RECK: a novel suppressor of malignancy linking oncogenic signaling to extracellular matrix remodeling. Cancer Metastasis Rev, 22, 167–175.

    Article  PubMed  CAS  Google Scholar 

  24. Rhee, J.S. and Coussens, L.M. (2002) RECKing MMP function: implications for cancer development. Trends Cell Biol, 12, 209–211.

    Article  PubMed  CAS  Google Scholar 

  25. Egeblad, M. and Werb, Z. (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer, 2, 161–174.

    Article  PubMed  CAS  Google Scholar 

  26. Span, P.N., Sweep, C.G., Manders, P., Beex, L.V., Leppert, D. and Lindberg, R.L. (2003) Matrix metalloproteinase inhibitor reversion-inducing cysteine-rich protein with Kazal motifs: a prognostic marker for good clinical outcome in human breast carcinoma. Cancer, 97, 2710–2715.

    Article  PubMed  CAS  Google Scholar 

  27. Antoniou, A.C. and Easton, D.F. (2003) Polygenic inheritance of breast cancer: implications for design of association studies. Genet Epidemiol, 25, 190–202.

    Article  PubMed  Google Scholar 

  28. Houlston, R.S. and Peto, J. (2003) The future of association studies of common cancers. Hum Genet, 112, 434–435.

    PubMed  Google Scholar 

  29. Hemminki, K., Vaittinen, P. and Easton, D. (2000) Familial cancer risks to offspring from mothers with 2 primary breast cancers: leads to cancer syndromes. Int J Cancer, 88, 87–91.

    Article  PubMed  CAS  Google Scholar 

  30. Försti, A., Jin, Q., Grzybowska, E., Soderberg, M., Zientek, H., Sieminska, M., Rogozinska-Szczepka, J., Chmielik, E., Utracka-Hutka, B. and Hemminki, K. (2002) Sex hormone-binding globulin polymorphisms in familial and sporadic breast cancer. Carcinogenesis, 23, 1315–1320.

    Article  PubMed  Google Scholar 

  31. Jin, Q., Hemminki, K., Grzybowska, E., Klaes, R., Soderberg, M. and Forsti, A. (2004) Re: Integrin beta3 Leu33Pro homozygosity and risk of cancer. J Natl Cancer Inst, 96, 234–235; author reply 235.

    Article  PubMed  CAS  Google Scholar 

  32. Jin, Q., Hemminki, K., Grzybowska, E., Klaes, R., Soderberg, M., Zientek, H., Rogozinska-Szczepka, J., Utracka-Hutka, B., Pamula, J., Pekala, W. and Forsti, A. (2004) Polymorphisms and haplotype structures in genes for transforming growth factor beta1 and its receptors in familial and unselected breast cancers. Int J Cancer, 112, 94–99.

    Article  PubMed  CAS  Google Scholar 

  33. Wagner, K., Hemminki, K., Israelsson, E., Grzybowska, E., Soderberg, M., Pamula, J., Pekala, W., Zientek, H., Mielzynska, D., Siwinska, E. and Forsti, A. (2005) Polymorphisms in the IGF-1 and IGFBP 3 promoter and the risk of breast cancer. Breast Cancer Res Treat, 92, 133–140.

    Article  PubMed  CAS  Google Scholar 

  34. Deal, C., Ma, J., Wilkin, F., Paquette, J., Rozen, F., Ge, B., Hudson, T., Stampfer, M. and Pollak, M. (2001) Novel promoter polymorphism in insulin-like growth factor-binding protein-3: correlation with serum levels and interaction with known regulators. J Clin Endocrinol Metab, 86, 1274–1280.

    Article  PubMed  CAS  Google Scholar 

  35. Plna, K. and Hemminki, K. (2001) Re: High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A mutation-positive melanoma families. J Natl Cancer Inst, 93, 323–325.

    Article  PubMed  CAS  Google Scholar 

  36. Gast, A., Forsti, A., Soderberg, M., Hemminki, K. and Kumar, R. (2005) B-RAF mutations in tumors from melanoma-breast cancer families. Int J Cancer, 113, 336–337.

    Article  PubMed  CAS  Google Scholar 

  37. Ahlbom, A., Lichtenstein, P., Malmström, H., Feychting, M., Hemminki, K. and Pedersen, N.L. (1997) Cancer in twins: genetic and nongenetic familial risk factors. J Natl Cancer Inst, 89, 287–293.

    Article  PubMed  CAS  Google Scholar 

  38. Försti, A., Luo, L., Vorechovsky, I., Söderberg, M., Lichtenstein, P. and Hemminki, K. (2001) Allelic imbalance on chromosomes 13 and 17 and mutation analysis of BRCA1 and BRCA2 genes in monozygotic twins concordant for breast cancer. Carcinogenesis, 22, 27–33.

    Article  PubMed  Google Scholar 

  39. Försti, A., Jin, Q., Sundqvist, L., Soderberg, M. and Hemminki, K. (2001) Use of monozygotic twins in search for breast cancer susceptibility loci. Twin Res, 4, 251–259.

    PubMed  Google Scholar 

  40. el-Rifai, W., Tarmo, L., Hemmer, S., Forsti, A., Pedersen, N., Lichtenstein, P., Ahlbom, A., Soderberg, M., Knuutila, S. and Hemminki, K. (1999) DNA copy number losses at 1p32-pter in monozygotic twins concordant for breast cancer. Cancer Genet Cytogenet, 112, 169–172.

    Article  PubMed  CAS  Google Scholar 

  41. Wacholder, S., Chanock, S., Garcia-Closas, M., El Ghormli, L. and Rothman, N. (2004) Assessing the probability that a positive report is false: an approach for molecular epidemiology studies. J Natl Cancer Inst, 96, 434–442.

    Article  PubMed  Google Scholar 

  42. Davey Smith, G., Ebrahim, S., Lewis, S., Hansell, A.L., Palmer, L.J. and Burton, P.R. (2005) Genetic epidemiology and public health: hope, hype, and future prospects. Lancet, 366, 1484–1498.

    Article  PubMed  Google Scholar 

  43. Hemminki, K. and Czene, K. (2002) Attributable risks of familial cancer from the Family-Cancer Database. Cancer Epidemiol Biomarkers Prev, 11, 1638–1644.

    PubMed  Google Scholar 

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Acknowledgments

Supported by Deutsche Krebshilfe, the Swedish Cancer Society and EU LSHC-CT-2004-503465.

Author information

Authors and Affiliations

  1. Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Asta Försti

  2. Center for Family and Community Medicine, Karolinska Institute, Huddinge, Sweden

    Asta Försti

  3. Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Karolinska Institute, Heidelberg, Germany

    Kari Hemminki

  4. K. Hemminki Center for Family and Community Medicine, Karolinska Institute, Huddinge, Sweden

    Kari Hemminki

Authors
  1. Asta Försti
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  2. Kari Hemminki
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Editors and Affiliations

  1. , Bio Banking and Molecular Resource, Karolinska Institutet, Stockholm, 205 02, Sweden

    Joakim Dillner

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Försti, A., Hemminki, K. (2011). Breast Cancer Genomics Based on Biobanks. In: Dillner, J. (eds) Methods in Biobanking. Methods in Molecular Biology, vol 675. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59745-423-0_23

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  • DOI: https://doi.org/10.1007/978-1-59745-423-0_23

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-58829-995-6

  • Online ISBN: 978-1-59745-423-0

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