Other Hereditary Breast Cancer Syndromes and Genes

  • Katherine L. Nathanson
Part of the Cancer Genetics book series (CANGENETICS)


The major genes associated with inherited susceptibility to breast cancer are BRCA1 and BRCA2. However, breast cancer is a component of other cancer susceptibility syndromes, including Li-Fraumeni syndrome, Cowden syndrome, Peutz-Jeghers syndrome and Hereditary Gastric Cancer. This chapter is divided into two major parts: (1) rare familial cancer syndromes with breast cancer as a component (Table 7.1) and (2) mutations in DNA damage response genes associated with an increased risk of breast cancer, notably in families with multiple breast cancer cases.


Breast Cancer Breast Cancer Risk Fanconi Anemia Breast Cancer Susceptibility Familial Breast Cancer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Li, F.P., and Fraumeni, J.F. (1969). Soft-tissue sarcomas, breast cancer, and other neoplasms: Familial syndrome? Ann Intern Med 71, 747.PubMedGoogle Scholar
  2. 2.
    Bougeard, G., Sesboue, R., Baert-Desurmont, S., Vasseur, S., Martin, C., Tinat, J., Brugieres, L., Chompret, A., de Paillerets, B.B., Stoppa-Lyonnet, D., et al. (2008). Molecular basis of the Li-Fraumeni syndrome: an update from the French LFS families. J Med Genet 45, 535–538.PubMedGoogle Scholar
  3. 3.
    Li, F.P., Fraumeni, J.F., and Mulvihill, J.J. (1988). A cancer family syndrome in 24 kindreds. Cancer Res 48, 5358.PubMedGoogle Scholar
  4. 4.
    Nichols, K.E., Malkin, D., Garber, J.E., Fraumeni, J.F., Jr., and Li, F.P. (2001). Germ-line p53 mutations predispose to a wide spectrum of early-onset cancers. Cancer Epidemiol Biomarkers Prev 10, 83–87.PubMedGoogle Scholar
  5. 5.
    Strong, L.C., Williams, W.R., and Tainsky, M.A. (1992). The Li-Fraumeni syndrome: from clinical epidemiology to molecular genetics. Am J Epidemiol 135, 190–199.PubMedGoogle Scholar
  6. 6.
    Hisada, M., Garber, J.E., Fung, C.Y., Fraumeni, J.F., Jr., and Li, F.P. (1998). Multiple primary cancers in families with Li-Fraumeni syndrome. J Natl Cancer Inst 90, 606–611.PubMedGoogle Scholar
  7. 7.
    Chompret, A., Brugieres, L., Ronsin, M., Gardes, M., Dessarps-Freichey, F., Abel, A., Hua, D., Ligot, L., Dondon, M.G., Bressac-de Paillerets, B., et al. (2000). P53 germline mutations in childhood cancers and cancer risk for carrier individuals. Br J Cancer 82, 1932–1937.PubMedGoogle Scholar
  8. 8.
    Wu, C.C., Shete, S., Amos, C.I., and Strong, L.C. (2006). Joint effects of germ-line p53 mutation and sex on cancer risk in Li-Fraumeni syndrome. Cancer Res 66, 8287–8292.PubMedGoogle Scholar
  9. 9.
    Malkin, D., Li, F.P., Strong, L.C., Fraumeni, J.F., Jr., Nelson, C.E., Kim, D.H., Kassel, J., Gryka, M.A., Bischoff, F.Z., Tainsky, M.A., et al. (1990). Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms [see comments]. Science 250, 1233–1238.PubMedGoogle Scholar
  10. 10.
    Srivastava, S., Zou, Z.Q., Pirollo, K., Blattner, W., and Chang, E.H. (1990). Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome [see comments]. Nature 348, 747–749.PubMedGoogle Scholar
  11. 11.
    Varley, J.M., McGown, G., Thorncroft, M., Santibanez-Koref, M.F., Kelsey, A.M., Tricker, K.J., Evans, D.G., and Birch, J.M. (1997). Germ-line mutations of TP53 in Li-Fraumeni families: an extended study of 39 families. Cancer Res 57, 3245–3252.PubMedGoogle Scholar
  12. 12.
    Law, J.C., Strong, L.C., Chidambaram, A., and Ferrell, R.E. (1991). A germ line mutation in exon 5 of the p53 gene in an extended cancer family. Cancer Res 51, 6385–6387.PubMedGoogle Scholar
  13. 13.
    Sameshima, Y., Tsunematsu, Y., Watanabe, S., Tsukamoto, T., Kawa-ha, K., Hirata, Y., Mizoguchi, H., Sugimura, T., Terada, M., and Yokota, J. (1992). Detection of novel germ-line p53 mutations in diverse-cancer-prone families identified by selecting patients with childhood adrenocortical carcinoma. J Natl Cancer Inst 84, 703–707.PubMedGoogle Scholar
  14. 14.
    Srivastava, S., Tong, Y.A., Devadas, K., Zou, Z.Q., Sykes, V.W., Chen, Y., Blattner, W.A., Pirollo, K., and Chang, E.H. (1992). Detection of both mutant and wild-type p53 protein in normal skin fibroblasts and demonstration of a shared ‘second hit’ on p53 in diverse tumors from a cancer-prone family with Li-Fraumeni syndrome. Oncogene 7, 987–991.PubMedGoogle Scholar
  15. 15.
    Barnes, D.M., Hanby, A.M., Gillett, C.E., Mohammed, S., Hodgson, S., Bobrow, L.G., Leigh, I.M., Purkis, T., MacGeoch, C., Spurr, N.K., et al. (1992). Abnormal expression of wild type p53 protein in normal cells of a cancer family patient. Lancet 340, 259–263.PubMedGoogle Scholar
  16. 16.
    Birch, J.M., Hartley, A.L., Tricker, K.J., Prosser, J., Condie, A., Kelsey, A.M., Harris, M., Jones, P.H., Binchy, A., Crowther, D., et al. (1994). Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families. Cancer Res 54, 1298–1304.PubMedGoogle Scholar
  17. 17.
    Varley, J.M., McGown, G., Thorncroft, M., Santibanez-Koref, M.F., Kelsey, A.M., Tricker, K.J., Evans, D.G., and Birch, J.M. (1997). Germ-line mutations of TP53 in Li-Fraumeni families: an extended study of 39 families. Cancer Res 57, 3245–3252.PubMedGoogle Scholar
  18. 18.
    Bachinski, L.L., Olufemi, S.E., Zhou, X., Wu, C.C., Yip, L., Shete, S., Lozano, G., Amos, C.I., Strong, L.C., and Krahe, R. (2005). Genetic mapping of a third Li-Fraumeni syndrome predisposition locus to human chromosome 1q23. Cancer Res 65, 427–431.PubMedGoogle Scholar
  19. 19.
    Masciari, S., Van den Abbeele, A.D., Diller, L.R., Rastarhuyeva, I., Yap, J., Schneider, K., Digianni, L., Li, F.P., Fraumeni, J.F., Jr., Syngal, S., et al. (2008). F18-fluorodeoxy glucose-positron emission tomography/computed tomography screening in Li-Fraumeni syndrome. JAMA 299, 1315–1319.PubMedGoogle Scholar
  20. 20.
    Limacher, J.M., Frebourg, T., Natarajan-Ame, S., and Bergerat, J.P. (2001). Two metachronous tumors in the radiotherapy fields of a patient with Li-Fraumeni syndrome. Int J Cancer 96, 238–242.PubMedGoogle Scholar
  21. 21.
    Borresen, A.L., Andersen, T.I., Garber, J., Barbier-Piraux, N., Thorlacius, S., Eyfjord, J., Ottestad, L., Smith-Sorensen, B., Hovig, E., Malkin, D., et al. (1992). Screening for germ line TP53 mutations in breast cancer patients. Cancer Res 52, 3234–3236.PubMedGoogle Scholar
  22. 22.
    Sidransky, D., Tokino, T., Helzlsouer, K., Zehnbauer, B., Rausch, G., Shelton, B., Prestigiacomo, L., Vogelstein, B., and Davidson, N. (1992). Inherited p53 gene mutations in breast cancer. Cancer Res 52, 2984–2986.PubMedGoogle Scholar
  23. 23.
    Lalloo, F., Varley, J., Ellis, D., Moran, A., O’Dair, L., Pharoah, P., and Evans, D.G. (2003). Prediction of pathogenic mutations in patients with early-onset breast cancer by family history. Lancet 361, 1101–1102.PubMedGoogle Scholar
  24. 24.
    Arcand, S.L., Maugard, C.M., Ghadirian, P., Robidoux, A., Perret, C., Zhang, P., Fafard, E., Mes-Masson, A.M., Foulkes, W.D., Provencher, D., et al. (2008). Germline TP53 mutations in BRCA1 and BRCA2 mutation-negative French Canadian breast cancer families. Breast Cancer Res Treat 108, 399–408.PubMedGoogle Scholar
  25. 25.
    Manoukian, S., Peissel, B., Pensotti, V., Barile, M., Cortesi, L., Stacchiotti, S., Terenziani, M., Barbera, F., Pasquini, G., Frigerio, S., et al. (2007). Germline mutations of TP53 and BRCA2 genes in breast cancer/sarcoma families. Eur J Cancer 43, 601–606.PubMedGoogle Scholar
  26. 26.
    Monnerat, C., Chompret, A., Kannengiesser, C., Avril, M.F., Janin, N., Spatz, A., Guinebretiere, J.M., Marian, C., Barrois, M., Boitier, F., et al. (2007). BRCA1, BRCA2, TP53, and CDKN2A germline mutations in patients with breast cancer and cutaneous melanoma. Fam Cancer 6, 453–461.PubMedGoogle Scholar
  27. 27.
    Rapakko, K., Allinen, M., Syrjakoski, K., Vahteristo, P., Huusko, P., Vahakangas, K., Eerola, H., Kainu, T., Kallioniemi, O.P., Nevanlinna, H., et al. (2001). Germline TP53 alterations in Finnish breast cancer families are rare and occur at conserved mutation-prone sites. Br J Cancer 84, 116–119.PubMedGoogle Scholar
  28. 28.
    Walsh, T., Casadei, S., Coats, K.H., Swisher, E., Stray, S.M., Higgins, J., Roach, K.C., Mandell, J., Lee, M.K., Ciernikova, S., et al. (2006). Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA 295, 1379–1388.PubMedGoogle Scholar
  29. 29.
    Buxbaum, J.D., Cai, G., Chaste, P., Nygren, G., Goldsmith, J., Reichert, J., Anckarsater, H., Rastam, M., Smith, C.J., Silverman, J.M., et al. (2007). Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly. Am J Med Genet B Neuropsychiatr Genet 144B, 484–491.PubMedGoogle Scholar
  30. 30.
    Eng, C. (2003). PTEN: one gene, many syndromes. Hum Mutat 22, 183–198.PubMedGoogle Scholar
  31. 31.
    Lachlan, K.L., Lucassen, A.M., Bunyan, D., and Temple, I.K. (2007). Cowden syndrome and Bannayan Riley Ruvalcaba syndrome represent one condition with variable expression and age-related penetrance: results of a clinical study of PTEN mutation carriers. J Med Genet 44, 579–585.PubMedGoogle Scholar
  32. 32.
    Orrico, A., Galli, L., Buoni, S., Orsi, A., Vonella, G., and Sorrentino, V. (2008). Novel PTEN mutations in neurodevelopmental disorders and macrocephaly. Clin Genet.Google Scholar
  33. 33.
    Marsh, D.J., Coulon, V., Lunetta, K.L., Rocca-Serra, P., Dahia, P.L., Zheng, Z., Liaw, D., Caron, S., Duboue, B., Lin, A.Y., et al. (1998). Mutation spectrum and genotype–phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation. Hum Mol Genet 7, 507–515.PubMedGoogle Scholar
  34. 34.
    Eng, C., Hampel, H., and de la Chapelle, A. (2001). Genetic testing for cancer predisposition. Annu Rev Med 52, 371–400.PubMedGoogle Scholar
  35. 35.
    Gustafson, S., Zbuk, K.M., Scacheri, C., and Eng, C. (2007). Cowden syndrome. Semin Oncol 34, 428–434.PubMedGoogle Scholar
  36. 36.
    Fackenthal, J.D., Marsh, D.J., Richardson, A.L., Cummings, S.A., Eng, C., Robinson, B.G., and Olopade, O.I. (2001). Male breast cancer in Cowden syndrome patients with germline PTEN mutations. J Med Genet 38, 159–164.PubMedGoogle Scholar
  37. 37.
    Hanssen, A.M., and Fryns, J.P. (1995). Cowden syndrome. J Med Genet 32, 117–119.PubMedGoogle Scholar
  38. 38.
    Starink, T.M., van der Veen, J.P., Arwert, F., de Waal, L.P., de Lange, G.G., Gille, J.J., and Eriksson, A.W. (1986). The Cowden syndrome: a clinical and genetic study in 21 patients. Clin Genet 29, 222–233.PubMedGoogle Scholar
  39. 39.
    Fargnoli, M.C., Orlow, S.J., Semel-Concepcion, J., and Bolognia, J.L. (1996). Clinicopathologic findings in the Bannayan-Riley-Ruvalcaba syndrome. Arch Dermatol 132, 1214–1218.PubMedGoogle Scholar
  40. 40.
    Nelen, M.R., Padberg, G.W., Peeters, E.A., Lin, A.Y., van den Helm, B., Frants, R.R., Coulon, V., Goldstein, A.M., van Reen, M.M., Easton, D.F., et al. (1996). Localization of the gene for Cowden disease to chromosome 10q22–23. Nat Genet 13, 114–116.PubMedGoogle Scholar
  41. 41.
    Eng, C., Murday, V., Seal, S., Mohammed, S., Hodgson, S.V., Chaudary, M.A., Fentiman, I.S., Ponder, B.A., and Eeles, R.A. (1994). Cowden syndrome and Lhermitte-Duclos disease in a family: a single genetic syndrome with pleiotropy? J Med Genet 31, 458–461.PubMedGoogle Scholar
  42. 42.
    Liaw, D., Marsh, D.J., Li, J., Dahia, P.L., Wang, S.I., Zheng, Z., Bose, S., Call, K.M., Tsou, H.C., Peacocke, M., et al. (1997). Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet 16, 64–67.PubMedGoogle Scholar
  43. 43.
    Goldgar, D.E., Teare, D., Shugart, Y., Stratton, M., and Easton, D. (1997). Candidate gene analysis and preliminary genomic search results for mapping of non-BRCA1/2 breast cancer genes. Am J Hum Genet 61, A66.Google Scholar
  44. 44.
    Carroll, B.T., Couch, F.J., Rebbeck, T.R., and Weber, B.L. (1999). Polymorphisms in PTEN in breast cancer families. J Med Genet 36, 94–96.PubMedGoogle Scholar
  45. 45.
    Figer, A., Kaplan, A., Frydman, M., Lev, D., Paswell, J., Papa, M.Z., Goldman, B., and Friedman, E. (2002). Germline mutations in the PTEN gene in Israeli patients with Bannayan-Riley-Ruvalcaba syndrome and women with familial breast cancer. Clin Genet 62, 298–302.PubMedGoogle Scholar
  46. 46.
    FitzGerald, M.G., Marsh, D.J., Wahrer, D., Bell, D., Caron, S., Shannon, K.E., Ishioka, C., Isselbacher, K.J., Garber, J.E., Eng, C., et al. (1998). Germline mutations in PTEN are an infrequent cause of genetic predisposition to breast cancer. Oncogene 17, 727–731.PubMedGoogle Scholar
  47. 47.
    Guenard, F., Labrie, Y., Ouellette, G., Beauparlant, C.J., Bessette, P., Chiquette, J., Laframboise, R., Lepine, J., Lesperance, B., Pichette, R., et al. (2007). Germline mutations in the breast cancer susceptibility gene PTEN are rare in high-risk non-BRCA1/2 French Canadian breast cancer families. Fam Cancer 6, 483–490.PubMedGoogle Scholar
  48. 48.
    Lynch, E.D., Ostermeyer, E.A., Lee, M.K., Arena, J.F., Ji, H., Dann, J., Swisshelm, K., Suchard, D., MacLeod, P.M., Kvinnsland, S., et al. (1997). Inherited mutations in PTEN that are associated with breast cancer, Cowden disease, and juvenile polyposis. Am J Hum Genet 61, 1254–1260.PubMedGoogle Scholar
  49. 49.
    Tsou, H.C., Teng, D.H., Ping, X.L., Brancolini, V., Davis, T., Hu, R., Xie, X.X., Gruener, A.C., Schrager, C.A., Christiano, A.M., et al. (1997). The role of MMAC1 mutations in early-onset breast cancer: causative in association with Cowden syndrome and excluded in BRCA1-negative cases. Am J Hum Genet 61, 1036–1043.PubMedGoogle Scholar
  50. 50.
    De Vivo, I., Gertig, D.M., Nagase, S., Hankinson, S.E., O’Brien, R., Speizer, F.E., Parsons, R., and Hunter, D.J. (2000). Novel germline mutations in the PTEN tumour suppressor gene found in women with multiple cancers. J Med Genet 37, 336–341.PubMedGoogle Scholar
  51. 51.
    McGarrity, T.J., and Amos, C. (2006). Peutz-Jeghers syndrome: clinicopathology and molecular alterations. Cell Mol Life Sci 63, 2135–2144.PubMedGoogle Scholar
  52. 52.
    Boardman, L.A., Couch, F.J., Burgart, L.J., Schwartz, D., Berry, R., McDonnell, S.K., Schaid, D.J., Hartmann, L.C., Schroeder, J.J., Stratakis, C.A., et al. (2000). Genetic heterogeneity in Peutz-Jeghers syndrome. Hum Mutat 16, 23–30.PubMedGoogle Scholar
  53. 53.
    Hemminki, A., Markie, D., Tomlinson, I., Avizienyte, E., Roth, S., Loukola, A., Bignell, G., Warren, W., Aminoff, M., Hoglund, P., et al. (1998). A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature 391, 184–187.PubMedGoogle Scholar
  54. 54.
    Lim, W., Olschwang, S., Keller, J.J., Westerman, A.M., Menko, F.H., Boardman, L.A., Scott, R.J., Trimbath, J., Giardiello, F.M., Gruber, S.B., et al. (2004). Relative frequency and morphology of cancers in STK11 mutation carriers. Gastroenterology 126, 1788–1794.PubMedGoogle Scholar
  55. 55.
    Mehenni, H., Gehrig, C., Nezu, J., Oku, A., Shimane, M., Rossier, C., Guex, N., Blouin, J.L., Scott, H.S., and Antonarakis, S.E. (1998). Loss of LKB1 kinase activity in Peutz-Jeghers syndrome, and evidence for allelic and locus heterogeneity. Am J Hum Genet 63, 1641–1650.PubMedGoogle Scholar
  56. 56.
    Olschwang, S., Markie, D., Seal, S., Neale, K., Phillips, R., Cottrell, S., Ellis, I., Hodgson, S., Zauber, P., Spigelman, A., et al. (1998). Peutz-Jeghers disease: most, but not all, families are compatible with linkage to 19p13.3. J Med Genet 35, 42–44.PubMedGoogle Scholar
  57. 57.
    Wang, Z.J., Churchman, M., Avizienyte, E., McKeown, C., Davies, S., Evans, D.G., Ferguson, A., Ellis, I., Xu, W.H., Yan, Z.Y., et al. (1999). Germline mutations of the LKB1 (STK11) gene in Peutz-Jeghers patients. J Med Genet 36, 365–368.PubMedGoogle Scholar
  58. 58.
    Ylikorkala, A., Avizienyte, E., Tomlinson, I.P., Tiainen, M., Roth, S., Loukola, A., Hemminki, A., Johansson, M., Sistonen, P., Markie, D., et al. (1999). Mutations and impaired function of LKB1 in familial and non-familial Peutz-Jeghers syndrome and a sporadic testicular cancer. Hum Mol Genet 8, 45–51.PubMedGoogle Scholar
  59. 59.
    Wang, Z.J., Ellis, I., Zauber, P., Iwama, T., Marchese, C., Talbot, I., Xue, W.H., Yan, Z.Y., and Tomlinson, I. (1999). Allelic imbalance at the LKB1 (STK11) locus in tumours from patients with Peutz-Jeghers’ syndrome provides evidence for a hamartoma-(adenoma)-carcinoma sequence. J Pathol 188, 9–13.PubMedGoogle Scholar
  60. 60.
    Bignell, G.R., Barfoot, R., Seal, S., Collins, N., Warren, W., and Stratton, M.R. (1998). Low frequency of somatic mutations in the LKB1/Peutz-Jeghers syndrome gene in sporadic breast cancer. Cancer Research 58, 1384–1386.PubMedGoogle Scholar
  61. 61.
    Hearle, N., Lucassen, A., Wang, R., Lim, W., Ross, F., Wheeler, R., Moore, I., Shipley, J., and Houlston, R. (2004). Mapping of a translocation breakpoint in a Peutz-Jeghers hamartoma to the putative PJS locus at 19q13.4 and mutation analysis of candidate genes in polyp and STK11-negative PJS cases. Genes Chromosomes Cancer 41, 163–169.PubMedGoogle Scholar
  62. 62.
    Mehenni, H., Blouin, J.L., Radhakrishna, U., Bhardwaj, S.S., Bhardwaj, K., Dixit, V.B., Richards, K.F., Bermejo-Fenoll, A., Leal, A.S., Raval, R.C., et al. (1997). Peutz-Jeghers syndrome: confirmation of linkage to chromosome 19p13.3 and identification of a potential second locus, on 19q13.4. Am J Hum Genet 61, 1327–1334.PubMedGoogle Scholar
  63. 63.
    Boardman, L.A., Thibodeau, S.N., Schaid, D.J., Lindor, N.M., McDonnell, S.K., Burgart, L.J., Ahlquist, D.A., Podratz, K.C., Pittelkow, M., and Hartmann, L.C. (1998). Increased risk for cancer in patients with the Peutz-Jeghers syndrome. Ann Intern Med 128, 896–899.PubMedGoogle Scholar
  64. 64.
    Hearle, N., Schumacher, V., Menko, F.H., Olschwang, S., Boardman, L.A., Gille, J.J., Keller, J.J., Westerman, A.M., Scott, R.J., Lim, W., et al. (2006). Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res 12, 3209–3215.PubMedGoogle Scholar
  65. 65.
    Mehenni, H., Resta, N., Park, J.G., Miyaki, M., Guanti, G., and Costanza, M.C. (2006). Cancer risks in LKB1 germline mutation carriers. Gut 55, 984–990.PubMedGoogle Scholar
  66. 66.
    Giardiello, F.M., Brensinger, J.D., Tersmette, A.C., Goodman, S.N., Petersen, G.M., Booker, S.V., Cruz-Correa, M., and Offerhaus, J.A. (2000). Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology 119, 1447–1453.PubMedGoogle Scholar
  67. 67.
    Pharoah, P.D., Guilford, P., and Caldas, C. (2001). Incidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families. Gastroenterology 121, 1348–1353.PubMedGoogle Scholar
  68. 68.
    Guilford, P., Hopkins, J., Harraway, J., McLeod, M., McLeod, N., Harawira, P., Taite, H., Scoular, R., Miller, A., and Reeve, A.E. (1998). E-cadherin germline mutations in familial gastric cancer. Nature 392, 402–405.PubMedGoogle Scholar
  69. 69.
    Brooks-Wilson, A.R., Kaurah, P., Suriano, G., Leach, S., Senz, J., Grehan, N., Butterfield, Y.S., Jeyes, J., Schinas, J., Bacani, J., et al. (2004). Germline E-cadherin mutations in hereditary diffuse gastric cancer: assessment of 42 new families and review of genetic screening criteria. J Med Genet 41, 508–517.PubMedGoogle Scholar
  70. 70.
    Suriano, G., Yew, S., Ferreira, P., Senz, J., Kaurah, P., Ford, J.M., Longacre, T.A., Norton, J.A., Chun, N., Young, S., et al. (2005). Characterization of a recurrent germ line mutation of the E-cadherin gene: implications for genetic testing and clinical management. Clin Cancer Res 11, 5401–5409.PubMedGoogle Scholar
  71. 71.
    Charlton, A., Blair, V., Shaw, D., Parry, S., Guilford, P., and Martin, I.G. (2004). Hereditary diffuse gastric cancer: predominance of multiple foci of signet ring cell carcinoma in distal stomach and transitional zone. Gut 53, 814–820.PubMedGoogle Scholar
  72. 72.
    Chun, Y.S., Lindor, N.M., Smyrk, T.C., Petersen, B.T., Burgart, L.J., Guilford, P.J., and Donohue, J.H. (2001). Germline E-cadherin gene mutations: is prophylactic total gastrectomy indicated? Cancer 92, 181–187.PubMedGoogle Scholar
  73. 73.
    Huntsman, D.G., Carneiro, F., Lewis, F.R., MacLeod, P.M., Hayashi, A., Monaghan, K.G., Maung, R., Seruca, R., Jackson, C.E., and Caldas, C. (2001). Early gastric cancer in young, asymptomatic carriers of germ-line E-cadherin mutations. N Engl J Med 344, 1904–1909.PubMedGoogle Scholar
  74. 74.
    Keller, G., Vogelsang, H., Becker, I., Hutter, J., Ott, K., Candidus, S., Grundei, T., Becker, K.F., Mueller, J., Siewert, J.R., et al. (1999). Diffuse type gastric and lobular breast carcinoma in a familial gastric cancer patient with an E-cadherin germline mutation. Am J Pathol 155, 337–342.Google Scholar
  75. 75.
    Zhu, Z.G., Yu, Y.Y., Zhang, Y., Ji, J., Zhang, J., Liu, B.Y., Chen, X.H., Lu, Y., Jiang, H.S., Bu, L., et al. (2004). Germline mutational analysis of CDH1 and pathologic features in familial cancer syndrome with diffuse gastric cancer/breast cancer proband in a Chinese family. Eur J Surg Oncol 30, 531–535.PubMedGoogle Scholar
  76. 76.
    Berx, G., Becker, K.F., Hofler, H., and van Roy, F. (1998). Mutations of the human E-cadherin (CDH1) gene. Hum Mutat 12, 226–237.PubMedGoogle Scholar
  77. 77.
    Berx, G., Cleton-Jansen, A.-M., Nollet, F., de Leeuw, W.J.F., van de Vijver, M.J., Cornelisse, C., and van Roy, F. (1995). E-cadherin is a tumour/invasion suppressor gene mutated in human lobular breast cancers. EMBO J 14, 6107–6116.PubMedGoogle Scholar
  78. 78.
    Kaurah, P., MacMillan, A., Boyd, N., Senz, J., De Luca, A., Chun, N., Suriano, G., Zaor, S., Van Manen, L., Gilpin, C., et al. (2007). Founder and recurrent CDH1 mutations in families with hereditary diffuse gastric cancer. JAMA 297, 2360–2372.PubMedGoogle Scholar
  79. 79.
    Masciari, S., Larsson, N., Senz, J., Boyd, N., Kaurah, P., Kandel, M.J., Harris, L.N., Pinheiro, H.C., Troussard, A., Miron, P., et al. (2007). Germline E-cadherin mutations in familial lobular breast cancer. J Med Genet 44, 726–731.PubMedGoogle Scholar
  80. 80.
    Schrader, K.A., Masciari, S., Boyd, N., Wiyrick, S., Kaurah, P., Senz, J., Burke, W., Lynch, H.T., Garber, J.E., and Huntsman, D.G. (2008). Hereditary diffuse gastric cancer: association with lobular breast cancer. Fam Cancer 7, 73–82.PubMedGoogle Scholar
  81. 81.
    Schelfout, K., Van Goethem, M., Kersschot, E., Verslegers, I., Biltjes, I., Leyman, P., Colpaert, C., Thienpont, L., Van den Haute, J., Gillardin, J.P., et al. (2004). Preoperative breast MRI in patients with invasive lobular breast cancer. Eur Radiol 14, 1209–1216.PubMedGoogle Scholar
  82. 82.
    Wright, J., Teraoka, S., Onengut, S., Tolun, A., Gatti, R.A., Ochs, H.D., and Concannon, P. (1996). A high frequency of distinct ATM gene mutations in ataxia-telangiectasia. Am J Hum Genet 59, 839–846.PubMedGoogle Scholar
  83. 83.
    Morrell, D., Cromartie, E., and Swift, M. (1986). Mortality and cancer incidence in 263 patients with ataxia-telangiectasia. J Natl Cancer Inst 77, 89–92.PubMedGoogle Scholar
  84. 84.
    Swift, M., Reitnauer, P.J., Morrell, D., and Chase, C.L. (1987). Breast and other cancers in families with ataxia-telangiectasia. New Engl J Med 316, 1289–1294.PubMedGoogle Scholar
  85. 85.
    Andrieu, N., Cavaciuti, E., Lauge, A., Ossian, K., Janin, N., Hall, J., and Stoppa-Lyonnet, D. (2005). Ataxia-telangiectasia genes and breast cancer risk in a French family study. J Dairy Res 72 Spec No, 73–80.PubMedGoogle Scholar
  86. 86.
    Cavaciuti, E., Lauge, A., Janin, N., Ossian, K., Hall, J., Stoppa-Lyonnet, D., and Andrieu, N. (2005). Cancer risk according to type and location of ATM mutation in ataxia-telangiectasia families. Genes Chromosomes Cancer 42, 1–9.PubMedGoogle Scholar
  87. 87.
    d’Almeida, A.K., Cavaciuti, E., Dondon, M.G., Lauge, A., Janin, N., Stoppa-Lyonnet, D., and Andrieu, N. (2005). Increased risk of breast cancer among female relatives of patients with ataxia-telangiectasia: a causal relationship? Br J Cancer 93, 730–732; author reply 732.PubMedGoogle Scholar
  88. 88.
    Easton, D.F. (1994). Cancer risks in A-T heterozygotes. Int J Radiat Biol 66, S177–182.PubMedGoogle Scholar
  89. 89.
    Inskip, H.M., Kinlen, L.J., Taylor, A.M., Woods, C.G., and Arlett, C.F. (1999). Risk of breast cancer and other cancers in heterozygotes for ataxia-telangiectasia. Br J Cancer 79, 1304–1307.PubMedGoogle Scholar
  90. 90.
    Janin, N., Andrieu, N., Ossian, K., Lauge, A., Croquette, M.F., Griscelli, C., Debre, M., Bressac-de-Paillerets, B., Aurias, A., and Stoppa-Lyonnet, D. (1999). Breast cancer risk in ataxia telangiectasia (AT) heterozygotes: haplotype study in French AT families. Br J Cancer 80, 1042–1045.PubMedGoogle Scholar
  91. 91.
    Olsen, J.H., Hanemann, J.M., Borresen-Dale, A.L., Brondum-Neilsen, K., Hammarstrom, L., Kleinerman, R., Kaarianen, H., Lonnqvist, T., Sankila, R., Seersholm, N., et al. (2001). Cancer in patients with ataxia-telangiectasia and in their relatives in the Nordic countries. J Natl Cancer Inst 93, 121–7.PubMedGoogle Scholar
  92. 92.
    Su, Y., and Swift, M. (2000). Mortality rates among carriers of ataxia-telangiectasia mutant alleles. Ann Intern Med 133, 770–778.PubMedGoogle Scholar
  93. 93.
    Swift, M., Morrell, D., Massey, R.B., and Chase, C.L. (1991). Incidence of cancer in 161 families affected by ataxia-telangiectasia [see comments]. New Engl J Med 325, 1831–1836.PubMedGoogle Scholar
  94. 94.
    Olsen, J.H., Hahnemann, J.M., Borresen-Dale, A.L., Tretli, S., Kleinerman, R., Sankila, R., Hammarstrom, L., Robsahm, T.E., Kaariainen, H., Bregard, A., et al . (2005). Breast and other cancers in 1445 blood relatives of 75 Nordic patients with ataxia telangiectasia. Br J Cancer 93, 260–265.PubMedGoogle Scholar
  95. 95.
    Thompson, D., Duedal, S., Kirner, J., McGuffog, L., Last, J., Reiman, A., Byrd, P., Taylor, M., and Easton, D.F. (2005). Cancer risks and mortality in heterozygous ATM mutation carriers. J Natl Cancer Inst 97, 813–822.PubMedGoogle Scholar
  96. 96.
    FitzGerald, M.G., Bean, J.M., Hegde, S.R., Unsal, H., MacDonald, D.J., Harkin, D.P., Finkelstein, D.M., Isselbacher, K.J., and Haber, D.A. (1997). Heterozygous ATM mutations do not contribute to early onset of breast cancer [see comments]. Nat Genet 15, 307–310.PubMedGoogle Scholar
  97. 97.
    Bebb, G., Glickman, B., Gelmon, K., and Gatti, R. (1997). “AT risk” for breast cancer [see comments]. Lancet 349, 1784–1785.PubMedGoogle Scholar
  98. 98.
    Chen, J., Birkholtz, G.G., Lindblom, P., Rubio, C., and Lindblom, A. (1998). The role of ataxia-telangiectasia heterozygotes in familial breast cancer. Cancer Res 58, 1376–1379.PubMedGoogle Scholar
  99. 99.
    Izatt, L., Greenman, J., Hodgson, S., Ellis, D., Watts, S., Scott, G., Jacobs, C., Liebmann, R., Zvelebil, M.J., Mathew, C., et al. (1999). Identification of germline missense mutations and rare allelic variants in the ATM gene in early-onset breast cancer. Genes, Chromosomes Cancer 26, 286–294.PubMedGoogle Scholar
  100. 100.
    Shayeghi, M., Seal, S., Regan, J., Collins, N., Barfoot, R., Rahman, N., Ashton, A., Moohan, M., Wooster, R., Owen, R., et al. (1998). Heterozygosity for mutations in the ataxia telangiectasia gene is not a major cause of radiotherapy complications in breast cancer patients. Br J Cancer 78, 922–927.PubMedGoogle Scholar
  101. 101.
    Vorechovsky, I., Luo, L., Lindblom, A., Negrini, M., Webster, A.D., Croce, C.M., and Hammarstrom, L. (1996). ATM mutations in cancer families. Cancer Res 56, 4130–4133.PubMedGoogle Scholar
  102. 102.
    Laake, K., Vu, P., Andersen, T.I., Erikstein, B., Karesen, R., Lonning, P.E., Skovlund, E., and Borresen-Dale, A.L. (2000). Screening breast cancer patients for Norwegian ATM mutations. Br J Cancer 83, 1650–1653.PubMedGoogle Scholar
  103. 103.
    Broeks, A., Urbanus, J.H., Floore, A.N., Dahler, E.C., Klijn, J.G., Rutgers, E.J., Devilee, P., Russell, N.S., van Leeuwen, F.E., and van’t Veer, L.J. (2000). ATM-heterozygous germline mutations contribute to breast cancer-susceptibility. Am J Hum Genet 66, 494–500.PubMedGoogle Scholar
  104. 104.
    Renwick, A., Thompson, D., Seal, S., Kelly, P., Chagtai, T., Ahmed, M., North, B., Jayatilake, H., Barfoot, R., Spanova, K., et al. (2006). ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles. Nat Genet 38, 873–875.PubMedGoogle Scholar
  105. 105.
    Bogdanova, N., Cybulski, C., Bermisheva, M., Datsyuk, I., Yamini, P., Hillemanns, P., Antonenkova, N.N., Khusnutdinova, E., Lubinski, J., and Dork, T. (2008). A nonsense mutation (E1978X) in the ATM gene is associated with breast cancer. Breast Cancer Res Treat.Google Scholar
  106. 106.
    Pylkas, K., Tommiska, J., Syrjakoski, K., Kere, J., Gatei, M., Waddell, N., Allinen, M., Karppinen, S.M., Rapakko, K., Kaariainen, H., et al. (2007). Evaluation of the role of Finnish ataxia-telangiectasia mutations in hereditary predisposition to breast cancer. Carcinogenesis 28, 1040–1045.PubMedGoogle Scholar
  107. 107.
    Concannon, P., Haile, R.W., Borresen-Dale, A.L., Rosenstein, B.S., Gatti, R.A., Teraoka, S.N., Diep, T.A., Jansen, L., Atencio, D.P., Langholz, B., et al. (2008). Variants in the ATM gene associated with a reduced risk of contralateral breast cancer. Cancer Res 68, 6486–6491.PubMedGoogle Scholar
  108. 108.
    D’Amours, D., and Jackson, S.P. (2002). The Mre11 complex: at the crossroads of DNA repair and checkpoint signalling. Nat Rev Mol Cell Biol 3, 317–327.PubMedGoogle Scholar
  109. 109.
    Lee, J.H., and Paull, T.T. (2004). Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex. Science 304, 93–96.PubMedGoogle Scholar
  110. 110.
    Lee, J.H., and Paull, T.T. (2005). ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex. Science 308, 551–554.PubMedGoogle Scholar
  111. 111.
    Stracker, T.H., Morales, M., Couto, S.S., Hussein, H., and Petrini, J.H. (2007). The carboxy terminus of NBS1 is required for induction of apoptosis by the MRE11 complex. Nature 447, 218–221.PubMedGoogle Scholar
  112. 112.
    Zhang, Y., Zhou, J., and Lim, C.U. (2006). The role of NBS1 in DNA double strand break repair, telomere stability, and cell cycle checkpoint control. Cell Res 16, 45–54.PubMedGoogle Scholar
  113. 113.
    Varon, R., Vissinga, C., Platzer, M., Cerosaletti, K.M., Chrzanowska, K.H., Saar, K., Beckmann, G., Seemanova, E., Cooper, P.R., Nowak, N.J., et al. (1998). Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell 93, 467–476.PubMedGoogle Scholar
  114. 114.
    Varon, R., Seemanova, E., Chrzanowska, K., Hnateyko, O., Piekutowska-Abramczuk, D., Krajewska-Walasek, M., Sykut-Cegielska, J., Sperling, K., and Reis, A. (2000). Clinical ascertainment of Nijmegen breakage syndrome (NBS) and prevalence of the major mutation, 657del5, in three Slav populations. Eur J Hum Genet 8, 900–902.PubMedGoogle Scholar
  115. 115.
    Bogdanova, N., Feshchenko, S., Schurmann, P., Waltes, R., Wieland, B., Hillemanns, P., Rogov, Y.I., Dammann, O., Bremer, M., Karstens, J.H., et al. (2008). Nijmegen Breakage Syndrome mutations and risk of breast cancer. Int J Cancer 122, 802–806.PubMedGoogle Scholar
  116. 116.
    Buslov, K.G., Iyevleva, A.G., Chekmariova, E.V., Suspitsin, E.N., Togo, A.V., Kuligina, E., Sokolenko, A.P., Matsko, D.E., Turkevich, E.A., Lazareva, Y.R., et al. (2005). NBS1 657del5 mutation may contribute only to a limited fraction of breast cancer cases in Russia. Int J Cancer 114, 585–589.PubMedGoogle Scholar
  117. 117.
    Gorski, B., Cybulski, C., Huzarski, T., Byrski, T., Gronwald, J., Jakubowska, A., Stawicka, M., Gozdecka-Grodecka, S., Szwiec, M., Urbanski, K., et al. (2005). Breast cancer predisposing alleles in Poland. Breast Cancer Res Treat 92, 19–24.PubMedGoogle Scholar
  118. 118.
    Gorski, B., Debniak, T., Masojc, B., Mierzejewski, M., Medrek, K., Cybulski, C., Jakubowska, A., Kurzawski, G., Chosia, M., Scott, R., et al. (2003). Germline 657del5 mutation in the NBS1 gene in breast cancer patients. Int J Cancer 106, 379–381.PubMedGoogle Scholar
  119. 119.
    Steffen, J., Nowakowska, D., Niwinska, A., Czapczak, D., Kluska, A., Piatkowska, M., Wisniewska, A., and Paszko, Z. (2006). Germline mutations 657del5 of the NBS1 gene contribute significantly to the incidence of breast cancer in Central Poland. Int J Cancer 119, 472–475.PubMedGoogle Scholar
  120. 120.
    Stewart, G.S., Maser, R.S., Stankovic, T., Bressan, D.A., Kaplan, M.I., Jaspers, N.G., Raams, A., Byrd, P.J., Petrini, J.H., and Taylor, A.M. (1999). The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder. Cell 99, 577–587.PubMedGoogle Scholar
  121. 121.
    Heikkinen, K., Karppinen, S.M., Soini, Y., Makinen, M., and Winqvist, R. (2003). Mutation screening of Mre11 complex genes: indication of RAD50 involvement in breast and ovarian cancer susceptibility. J Med Genet 40, e131.PubMedGoogle Scholar
  122. 122.
    Heikkinen, K., Rapakko, K., Karppinen, S.M., Erkko, H., Knuutila, S., Lundan, T., Mannermaa, A., Borresen-Dale, A.L., Borg, A., Barkardottir, R.B., et al. (2006). RAD50 and NBS1 are breast cancer susceptibility genes associated with genomic instability. Carcinogenesis 27, 1593–1599.PubMedGoogle Scholar
  123. 123.
    Hsu, H.M., Wang, H.C., Chen, S.T., Hsu, G.C., Shen, C.Y., and Yu, J.C. (2007). Breast cancer risk is associated with the genes encoding the DNA double-strand break repair Mre11/Rad50/Nbs1 complex. Cancer Epidemiol Biomarkers Prev 16, 2024–2032.PubMedGoogle Scholar
  124. 124.
    Tommiska, J., Seal, S., Renwick, A., Barfoot, R., Baskcomb, L., Jayatilake, H., Bartkova, J., Tallila, J., Kaare, M., Tamminen, A., et al. (2006). Evaluation of RAD50 in familial breast cancer predisposition. Int J Cancer 118, 2911–2916.PubMedGoogle Scholar
  125. 125.
    Bartek, J., and Lukas, J. (2003). Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell 3, 421–429.PubMedGoogle Scholar
  126. 126.
    Ahn, J.Y., Schwarz, J.K., Piwnica-Worms, H., and Canman, C.E. (2000). Threonine 68 phosphorylation by ataxia telangiectasia mutated is required for efficient activation of Chk2 in response to ionizing radiation. Cancer Res 60, 5934–5936.PubMedGoogle Scholar
  127. 127.
    Matsuoka, S., Huang, M., and Elledge, S.J. (1998). Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Science 282, 1893–1897.PubMedGoogle Scholar
  128. 128.
    Matsuoka, S., Rotman, G., Ogawa, A., Shiloh, Y., Tamai, K., and Elledge, S.J. (2000). Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro. Proc Natl Acad Sci U S A 97, 10389–10394.PubMedGoogle Scholar
  129. 129.
    McPherson, J.P., Lemmers, B., Hirao, A., Hakem, A., Abraham, J., Migon, E., Matysiak-Zablocki, E., Tamblyn, L., Sanchez-Sweatman, O., Khokha, R., et al. (2004). Collaboration of Brca1 and Chk2 in tumorigenesis. Genes Dev 18, 1144–1153.PubMedGoogle Scholar
  130. 130.
    Zhang, J., Willers, H., Feng, Z., Ghosh, J.C., Kim, S., Weaver, D.T., Chung, J.H., Powell, S.N., and Xia, F. (2004). Chk2 phosphorylation of BRCA1 regulates DNA double-strand break repair. Mol Cell Biol 24, 708–718.PubMedGoogle Scholar
  131. 131.
    Bell, D.W., Varley, J.M., Szydlo, T.E., Kang, D.H., Wahrer, D.C., Shannon, K.E., Lubratovich, M., Verselis, S.J., Isselbacher, K.J., Fraumeni, J.F., et al. (1999). Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. Science 286, 2528–2531.PubMedGoogle Scholar
  132. 132.
    Broeks, A., de Witte, L., Nooijen, A., Huseinovic, A., Klijn, J.G., van Leeuwen, F.E., Russell, N.S., and van’t Veer, L.J. (2004). Excess risk for contralateral breast cancer in CHEK2*1100delC germline mutation carriers. Breast Cancer Res Treat 83, 91–93.PubMedGoogle Scholar
  133. 133.
    Consortium, C.B.C.C.-C. (2004). CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies. Am J Hum Genet 74, 1175–1182.Google Scholar
  134. 134.
    Lee, S.B., Kim, S.H., Bell, D.W., Wahrer, D.C., Schiripo, T.A., Jorczak, M.M., Sgroi, D.C., Garber, J.E., Li, F.P., Nichols, K.E., et al. (2001). Destabilization of CHK2 by a missense mutation associated with Li-Fraumeni Syndrome. Cancer Res 61, 8062–8067.PubMedGoogle Scholar
  135. 135.
    Meijers-Heijboer, H., van den Ouweland, A., Klijn, J., Wasielewski, M., de Snoo, A., Oldenburg, R., Hollestelle, A., Houben, M., Crepin, E., van Veghel-Plandsoen, M., et al. (2002). Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet 31, 55–59.PubMedGoogle Scholar
  136. 136.
    Offit, K., Pierce, H., Kirchhoff, T., Kolachana, P., Rapaport, B., Gregersen, P., Johnson, S., Yossepowitch, O., Huang, H., Satagopan, J., et al. (2003). Frequency of CHEK2*1100delC in New York breast cancer cases and controls. BMC Med Genet 4, 1.PubMedGoogle Scholar
  137. 137.
    Oldenburg, R.A., Kroeze-Jansema, K., Kraan, J., Morreau, H., Klijn, J.G., Hoogerbrugge, N., Ligtenberg, M.J., van Asperen, C.J., Vasen, H.F., Meijers, C., et al. (2003). The CHEK2*1100delC variant acts as a breast cancer risk modifier in non-BRCA1/BRCA2 multiple-case families. Cancer Res 63, 8153–8157.PubMedGoogle Scholar
  138. 138.
    Osorio, A., Rodriguez-Lopez, R., Diez, O., de la Hoya, M., Ignacio Martinez, J., Vega, A., Esteban-Cardenosa, E., Alonso, C., Caldes, T., and Benitez, J. (2004). The breast cancer low-penetrance allele 1100delC in the CHEK2 gene is not present in Spanish familial breast cancer population. Int J Cancer 108, 54–56.PubMedGoogle Scholar
  139. 139.
    Rajkumar, T., Soumittra, N., Nancy, N.K., Swaminathan, R., Sridevi, V., and Shanta, V. (2003). BRCA1, BRCA2 and CHEK2 (1100 del C) germline mutations in hereditary breast and ovarian cancer families in South India. Asian Pac J Cancer Prev 4, 203–208.PubMedGoogle Scholar
  140. 140.
    Sodha, N., Bullock, S., Taylor, R., Mitchell, G., Guertl-Lackner, B., Williams, R.D., Bevan, S., Bishop, K., McGuire, S., Houlston, R.S., et al. (2002). CHEK2 variants in susceptibility to breast cancer and evidence of retention of the wild type allele in tumours. Br J Cancer 87, 1445–1448.PubMedGoogle Scholar
  141. 141.
    Vahteristo, P., Bartkova, J., Eerola, H., Syrjakoski, K., Ojala, S., Kilpivaara, O., Tamminen, A., Kononen, J., Aittomaki, K., Heikkila, P., et al. (2002). A CHEK2 genetic variant contributing to a substantial fraction of familial breast cancer. Am J Hum Genet 71, 432–438.PubMedGoogle Scholar
  142. 142.
    Schmidt, M.K., Tollenaar, R.A., de Kemp, S.R., Broeks, A., Cornelisse, C.J., Smit, V.T., Peterse, J.L., van Leeuwen, F.E., and Van’t Veer, L.J. (2007). Breast cancer survival and tumor characteristics in premenopausal women carrying the CHEK2*1100delC germline mutation. J Clin Oncol 25, 64–69.PubMedGoogle Scholar
  143. 143.
    Weischer, M., Bojesen, S.E., Ellervik, C., Tybjaerg-Hansen, A., and Nordestgaard, B.G. (2008). CHEK2*1100delC genotyping for clinical assessment of breast cancer risk: meta-analyses of 26,000 patient cases and 27,000 controls. J Clin Oncol 26, 542–548.PubMedGoogle Scholar
  144. 144.
    Offit, K., and Garber, J.E. (2008). Time to check CHEK2 in families with breast cancer? J Clin Oncol 26, 519–520.PubMedGoogle Scholar
  145. 145.
    Bernstein, J.L., Teraoka, S.N., John, E.M., Andrulis, I.L., Knight, J.A., Lapinski, R., Olson, E.R., Wolitzer, A.L., Seminara, D., Whittemore, A.S., et al. (2006). The CHEK2*1100delC allelic variant and risk of breast cancer: screening results from the Breast Cancer Family Registry. Cancer Epidemiol Biomarkers Prev 15, 348–352.PubMedGoogle Scholar
  146. 146.
    Mellemkjaer, L., Dahl, C., Olsen, J.H., Bertelsen, L., Guldberg, P., Christensen, J., Borresen-Dale, A.L., Stovall, M., Langholz, B., Bernstein, L., et al. (2008). Risk for contralateral breast cancer among carriers of the CHEK2*1100delC mutation in the WECARE Study. Br J Cancer 98, 728–733.PubMedGoogle Scholar
  147. 147.
    Johnson, N., Fletcher, O., Naceur-Lombardelli, C., dos Santos Silva, I., Ashworth, A., and Peto, J. (2005). Interaction between CHEK2*1100delC and other low-penetrance breast-cancer susceptibility genes: a familial study. Lancet 366, 1554–1557.PubMedGoogle Scholar
  148. 148.
    Narod, S.A., and Lynch, H.T. (2007). CHEK2 mutation and hereditary breast cancer. J Clin Oncol 25, 6–7.PubMedGoogle Scholar
  149. 149.
    Schutte, M., Seal, S., Barfoot, R., Meijers-Heijboer, H., Wasielewski, M., Evans, D.G., Eccles, D., Meijers, C., Lohman, F., Klijn, J., et al. (2003). Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility. Am J Hum Genet 72, 1023–1028.PubMedGoogle Scholar
  150. 150.
    Bogdanova, N., Enssen-Dubrowinskaja, N., Feshchenko, S., Lazjuk, G.I., Rogov, Y.I., Dammann, O., Bremer, M., Karstens, J.H., Sohn, C., and Dork, T. (2005). Association of two mutations in the CHEK2 gene with breast cancer. Int J Cancer 116, 263–266.PubMedGoogle Scholar
  151. 151.
    Cybulski, C., Gorski, B., Huzarski, T., Byrski, T., Gronwald, J., Debniak, T., Wokolorczyk, D., Jakubowska, A., Kowalska, E., Oszurek, O., et al. (2006). CHEK2-positive breast cancers in young Polish women. Clin Cancer Res 12, 4832–4835.PubMedGoogle Scholar
  152. 152.
    Cybulski, C., Gorski, B., Huzarski, T., Masojc, B., Mierzejewski, M., Debniak, T., Teodorczyk, U., Byrski, T., Gronwald, J., Matyjasik, J., et al. (2004). CHEK2 is a multiorgan cancer susceptibility gene. Am J Hum Genet 75, 1131–1135.PubMedGoogle Scholar
  153. 153.
    Kilpivaara, O., Vahteristo, P., Falck, J., Syrjakoski, K., Eerola, H., Easton, D., Bartkova, J., Lukas, J., Heikkila, P., Aittomaki, K., et al. (2004). CHEK2 variant I157T may be associated with increased breast cancer risk. Int J Cancer 111, 543–547.PubMedGoogle Scholar
  154. 154.
    Cybulski, C., Wokolorczyk, D., Huzarski, T., Byrski, T., Gronwald, J., Gorski, B., Debniak, T., Masojc, B., Jakubowska, A., van de Wetering, T., et al. (2007). A deletion in CHEK2 of 5,395 bp predisposes to breast cancer in Poland. Breast Cancer Res Treat 102, 119–122.PubMedGoogle Scholar
  155. 155.
    Wu, L.C., Wang, Z.W., Tsan, J.T., Spillman, M.A., Phung, A., Xu, X.L., Yang, M.C., Hwang, L.Y., Bowcock, A.M., and Baer, R. (1996). Identification of a RING protein that can interact in vivo with the BRCA1 gene product. Nat Genet 14, 430–440.PubMedGoogle Scholar
  156. 156.
    Meza, J.E., Brzovic, P.S., King, M.C., and Klevit, R.E. (1999). Mapping the functional domains of BRCA1. Interaction of the ring finger domains of BRCA1 and BARD1. J Biol Chem 274, 5659–5665.PubMedGoogle Scholar
  157. 157.
    Brzovic, P.S., Meza, J., King, M.C., and Klevit, R.E. (1998). The cancer-predisposing mutation C61G disrupts homodimer formation in the NH2-terminal BRCA1 RING finger domain. J Biol Chem 273, 7795–7799.PubMedGoogle Scholar
  158. 158.
    Irminger-Finger, I., and Jefford, C.E. (2006). Is there more to BARD1 than BRCA1? Nat Rev Cancer 6, 382–391.PubMedGoogle Scholar
  159. 159.
    McCarthy, E.E., Celebi, J.T., Baer, R., and Ludwig, T. (2003). Loss of Bard1, the heterodimeric partner of the Brca1 tumor suppressor, results in early embryonic lethality and chromosomal instability. Mol Cell Biol 23, 5056–5063.PubMedGoogle Scholar
  160. 160.
    Shakya, R., Szabolcs, M., McCarthy, E., Ospina, E., Basso, K., Nandula, S., Murty, V., Baer, R., and Ludwig, T. (2008). The basal-like mammary carcinomas induced by Brca1 or Bard1 inactivation implicate the BRCA1/BARD1 heterodimer in tumor suppression. Proc Natl Acad Sci U S A 105, 7040–7045.PubMedGoogle Scholar
  161. 161.
    Ghimenti, C., Sensi, E., Presciuttini, S., Brunetti, I.M., Conte, P., Bevilacqua, G., and Caligo, M.A. (2002). Germline mutations of the BRCA1-associated ring domain (BARD1) gene in breast and breast/ovarian families negative for BRCA1 and BRCA2 alterations. Genes Chromosomes Cancer 33, 235–242.PubMedGoogle Scholar
  162. 162.
    Ishitobi, M., Miyoshi, Y., Hasegawa, S., Egawa, C., Tamaki, Y., Monden, M., and Noguchi, S. (2003). Mutational analysis of BARD1 in familial breast cancer patients in Japan. Cancer Lett 200, 1–7.PubMedGoogle Scholar
  163. 163.
    Vahteristo, P., Syrjakoski, K., Heikkinen, T., Eerola, H., Aittomaki, K., von Smitten, K., Holli, K., Blomqvist, C., Kallioniemi, O.P., and Nevanlinna, H. (2006). BARD1 variants Cys557Ser and Val507Met in breast cancer predisposition. Eur J Hum Genet 14, 167–172.PubMedGoogle Scholar
  164. 164.
    Karppinen, S.M., Heikkinen, K., Rapakko, K., and Winqvist, R. (2004). Mutation screening of the BARD1 gene: evidence for involvement of the Cys557Ser allele in hereditary susceptibility to breast cancer. J Med Genet 41, e114.PubMedGoogle Scholar
  165. 165.
    Johnatty, S.E., Beesley, J., Chen, X., Hopper, J.L., Southey, M.C., Giles, G.G., Goldgar, D.E., Chenevix-Trench, G., and Spurdle, A.B. (2008). The BARD1 Cys557Ser polymorphism and breast cancer risk: an Australian case–control and family analysis. Breast Cancer Res Treat.Google Scholar
  166. 166.
    Jakubowska, A., Cybulski, C., Szymanska, A., Huzarski, T., Byrski, T., Gronwald, J., Debniak, T., Gorski, B., Kowalska, E., Narod, S.A., et al. (2008). BARD1 and breast cancer in Poland. Breast Cancer Res Treat 107, 119–122.PubMedGoogle Scholar
  167. 167.
    Stacey, S.N., Sulem, P., Johannsson, O.T., Helgason, A., Gudmundsson, J., Kostic, J.P., Kristjansson, K., Jonsdottir, T., Sigurdsson, H., Hrafnkelsson, J., et al. (2006). The BARD1 Cys557Ser variant and breast cancer risk in Iceland. PLoS Med 3, e217.PubMedGoogle Scholar
  168. 168.
    Karppinen, S.M., Barkardottir, R.B., Backenhorn, K., Sydenham, T., Syrjakoski, K., Schleutker, J., Ikonen, T., Pylkas, K., Rapakko, K., Erkko, H., et al. (2006). Nordic collaborative study of the BARD1 Cys557Ser allele in 3956 patients with cancer: enrichment in familial BRCA1/BRCA2 mutation-negative breast cancer but not in other malignancies. J Med Genet 43, 856–862.PubMedGoogle Scholar
  169. 169.
    Kutler, D.I., Singh, B., Satagopan, J., Batish, S.D., Berwick, M., Giampietro, P.F., Hanenberg, H., and Auerbach, A.D. (2003). A 20-year perspective on the International Fanconi Anemia Registry (IFAR). Blood 101, 1249–1256.PubMedGoogle Scholar
  170. 170.
    Wagner, J.E., Tolar, J., Levran, O., Scholl, T., Deffenbaugh, A., Satagopan, J., Ben-Porat, L., Mah, K., Batish, S.D., Kutler, D.I., et al. (2004). Germline mutations in BRCA2: shared genetic susceptibility to breast cancer, early onset leukemia, and Fanconi anemia. Blood 103, 3226–3229.PubMedGoogle Scholar
  171. 171.
    Alter, B.P., Rosenberg, P.S., and Brody, L.C. (2007). Clinical and molecular features associated with biallelic mutations in FANCD1/BRCA2. J Med Genet 44, 1–9.PubMedGoogle Scholar
  172. 172.
    Reid, S., Renwick, A., Seal, S., Baskcomb, L., Barfoot, R., Jayatilake, H., Pritchard-Jones, K., Stratton, M.R., Ridolfi-Luthy, A., and Rahman, N. (2005). Biallelic BRCA2 mutations are associated with multiple malignancies in childhood including familial Wilms tumour. J Med Genet 42, 147–151.PubMedGoogle Scholar
  173. 173.
    Reid, S., Schindler, D., Hanenberg, H., Barker, K., Hanks, S., Kalb, R., Neveling, K., Kelly, P., Seal, S., Freund, M., et al. (2006). Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer. Nat Genet.Google Scholar
  174. 174.
    Taniguchi, T., and D’Andrea, A.D. (2006). Molecular pathogenesis of Fanconi anemia: recent progress. Blood 107, 4223–4233.PubMedGoogle Scholar
  175. 175.
    Swift, M., Caldwell, R.J., and Chase, C. (1980). Reassessment of cancer predisposition of Fanconi anemia heterozygotes. J Natl Cancer Inst 65, 863–867.PubMedGoogle Scholar
  176. 176.
    Potter, N.U., Sarmousakis, C., and Li, F.P. (1983). Cancer in relatives of patients with aplastic anemia. Cancer Genet Cytogenet 9, 61–65.PubMedGoogle Scholar
  177. 177.
    Howlett, N.G., Taniguchi, T., Olson, S., Cox, B., Waisfisz, Q., De Die-Smulders, C., Persky, N., Grompe, M., Joenje, H., Pals, G., et al. (2002). Biallelic inactivation of BRCA2 in Fanconi anemia [see comment]. Science 297, 606–609.PubMedGoogle Scholar
  178. 178.
    Seal, S., Barfoot, R., Jayatilake, H., Smith, P., Renwick, A., Bascombe, L., McGuffog, L., Evans, D.G., Eccles, D., Easton, D.F., et al. (2003). Evaluation of Fanconi Anemia genes in familial breast cancer predisposition. Cancer Res 63, 8596–8599.PubMedGoogle Scholar
  179. 179.
    Lewis, A.G., Flanagan, J., Marsh, A., Pupo, G.M., Mann, G., Spurdle, A.B., Lindeman, G.J., Visvader, J.E., Brown, M.A., and Chenevix-Trench, G. (2005). Mutation analysis of FANCD2, BRIP1/BACH1, LMO4 and SFN in familial breast cancer. Breast Cancer Res 7, R1005–1016.PubMedGoogle Scholar
  180. 180.
    Karppinen, S.M., Vuosku, J., Heikkinen, K., Allinen, M., and Winqvist, R. (2003). No evidence of involvement of germline BACH1 mutations in Finnish breast and ovarian cancer families. Eur J Cancer 39, 366–371.PubMedGoogle Scholar
  181. 181.
    Levran, O., Attwooll, C., Henry, R.T., Milton, K.L., Neveling, K., Rio, P., Batish, S.D., Kalb, R., Velleuer, E., Barral, S., et al. (2005). The BRCA1-interacting helicase BRIP1 is deficient in Fanconi anemia. Nat Genet 37, 931–933.PubMedGoogle Scholar
  182. 182.
    Litman, R., Peng, M., Jin, Z., Zhang, F., Zhang, J., Powell, S., Andreassen, P.R., and Cantor, S.B. (2005). BACH1 is critical for homologous recombination and appears to be the Fanconi anemia gene product FANCJ. Cancer Cell 8, 255–265.PubMedGoogle Scholar
  183. 183.
    Luo, L., Lei, H., Du, Q., von Wachenfeldt, A., Kockum, I., Luthman, H., Vorechovsky, I., and Lindblom, A. (2002). No mutations in the BACH1 gene in BRCA1 and BRCA2 negative breast-cancer families linked to 17q22. Int J Cancer 98, 638–639.PubMedGoogle Scholar
  184. 184.
    Rutter, J.L., Smith, A.M., Davila, M.R., Sigurdson, A.J., Giusti, R.M., Pineda, M.A., Doody, M.M., Tucker, M.A., Greene, M.H., Zhang, J., et al. (2003). Mutational analysis of the BRCA1-interacting genes ZNF350/ZBRK1 and BRIP1/BACH1 among BRCA1 and BRCA2-negative probands from breast–ovarian cancer families and among early-onset breast cancer cases and reference individuals. Hum Mutat 22, 121–128.PubMedGoogle Scholar
  185. 185.
    Seal, S., Thompson, D., Renwick, A., Elliott, A., Kelly, P., Barfoot, R., Chagtai, T., Jayatilake, H., Ahmed, M., Spanova, K., et al. (2006). Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles. Nat Genet 38, 1239–1241.PubMedGoogle Scholar
  186. 186.
    Cao, A.Y., Huang, J., Hu, Z., Li, W.F., Ma, Z.L., Tang, L.L., Zhang, B., Su, F.X., Zhou, J., Di, G.H., et al. (2008). Mutation analysis of BRIP1/BACH1 in BRCA1/BRCA2 negative Chinese women with early onset breast cancer or affected relatives. Breast Cancer Res Treat.Google Scholar
  187. 187.
    De Nicolo, A., Tancredi, M., Lombardi, G., Flemma, C.C., Barbuti, S., Di Cristofano, C., Sobhian, B., Bevilacqua, G., Drapkin, R., and Caligo, M.A. (2008). A novel breast cancer-associated BRIP1 (FANCJ/BACH1) germ-line mutation impairs protein stability and function. Clin Cancer Res 14, 4672–4680.PubMedGoogle Scholar
  188. 188.
    Guenard, F., Labrie, Y., Ouellette, G., Joly Beauparlant, C., Simard, J., and Durocher, F. (2008). Mutational analysis of the breast cancer susceptibility gene BRIP1 /BACH1/FANCJ in high-risk non-BRCA1/BRCA2 breast cancer families. J Hum Genet 53, 579–591.PubMedGoogle Scholar
  189. 189.
    Song, H., Ramus, S.J., Kjaer, S.K., Hogdall, E., Dicioccio, R.A., Whittemore, A.S., McGuire, V., Hogdall, C., Jacobs, I.J., Easton, D.F., et al. (2007). Tagging single nucleotide polymorphisms in the BRIP1 gene and susceptibility to breast and ovarian cancer. PLoS ONE 2, e268.PubMedGoogle Scholar
  190. 190.
    Xia, B., Sheng, Q., Nakanishi, K., Ohashi, A., Wu, J., Christ, N., Liu, X., Jasin, M., Couch, F.J., and Livingston, D.M. (2006). Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2. Mol Cell 22, 719–729.PubMedGoogle Scholar
  191. 191.
    Rahman, N., Seal, S., Thompson, D., Kelly, P., Renwick, A., Elliott, A., Reid, S., Spanova, K., Barfoot, R., Chagtai, T., et al. (2007). PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat Genet 39, 165–167.PubMedGoogle Scholar
  192. 192.
    Cao, A.Y., Huang, J., Hu, Z., Li, W.F., Ma, Z.L., Tang, L.L., Zhang, B., Su, F.X., Zhou, J., Di, G.H., et al. (2008). The prevalence of PALB2 germline mutations in BRCA1/BRCA2 negative Chinese women with early onset breast cancer or affected relatives. Breast Cancer Res Treat.Google Scholar
  193. 193.
    Foulkes, W.D., Ghadirian, P., Akbari, M.R., Hamel, N., Giroux, S., Sabbaghian, N., Darnel, A., Royer, R., Poll, A., Fafard, E., et al. (2007). Identification of a novel truncating PALB2 mutation and analysis of its contribution to early-onset breast cancer in French-Canadian women. Breast Cancer Res 9, R83.PubMedGoogle Scholar
  194. 194.
    Garcia, M.J., Fernandez, V., Osorio, A., Barroso, A., Llort, G., Lazaro, C., Blanco, I., Caldes, T., de la Hoya, M., Ramon, Y.C.T., et al. (2008). Analysis of FANCB and FANCN/PALB2 Fanconi Anemia genes in BRCA1/2-negative Spanish breast cancer families. Breast Cancer Res Treat.Google Scholar
  195. 195.
    Gunnarsson, H., Arason, A., Gillanders, E.M., Agnarsson, B.A., Johannesdottir, G., Johannsson, O.T., and Barkardottir, R.B. (2008). Evidence against PALB2 involvement in Icelandic breast cancer susceptibility. J Negat Results Biomed 7, 5.PubMedGoogle Scholar
  196. 196.
    Tischkowitz, M., Xia, B., Sabbaghian, N., Reis-Filho, J.S., Hamel, N., Li, G., van Beers, E.H., Li, L., Khalil, T., Quenneville, L.A., et al. (2007). Analysis of PALB2/FANCN-associated breast cancer families. Proc Natl Acad Sci U S A 104, 6788–6793.PubMedGoogle Scholar
  197. 197.
    Erkko, H., Xia, B., Nikkila, J., Schleutker, J., Syrjakoski, K., Mannermaa, A., Kallioniemi, A., Pylkas, K., Karppinen, S.M., Rapakko, K., et al. (2007). A recurrent mutation in PALB2 in Finnish cancer families. Nature 446, 316–319.PubMedGoogle Scholar
  198. 198.
    Erkko, H., Dowty, J.G., Nikkila, J., Syrjakoski, K., Mannermaa, A., Pylkas, K., Southey, M.C., Holli, K., Kallioniemi, A., Jukkola-Vuorinen, A., et al. (2008). Penetrance analysis of the PALB2 c.1592delT founder mutation. Clin Cancer Res 14, 4667–4671.PubMedGoogle Scholar
  199. 199.
    Chen, P., Liang, J., Wang, Z., Zhou, X., Chen, L., Li, M., Xie, D., Hu, Z., Shen, H., and Wang, H. (2008). Association of common PALB2 polymorphisms with breast cancer risk: a case–control study. Clin Cancer Res 14, 5931–5937.PubMedGoogle Scholar
  200. 200.
    Potapova, A., Hoffman, A.M., Godwin, A.K., Al-Saleem, T., and Cairns, P. (2008). Promoter hypermethylation of the PALB2 susceptibility gene in inherited and sporadic breast and ovarian cancer. Cancer Res 68, 998–1002.PubMedGoogle Scholar
  201. 201.
    Cybulski, C., Wokolorczyk, D., Huzarski, T., Byrski, T., Gronwald, J., Gorski, B., Debniak, T., Masojc, B., Jakubowska, A., Gliniewicz, B., et al. (2006). A large germline deletion in the Chek2 kinase gene is associated w ith an increased risk of prostate cancer. J Med Genet 43, 863–866.PubMedGoogle Scholar
  202. 202.
    Dong, X., Wang, L., Taniguchi, K., Wang, X., Cunningham, J.M., McDonnell, S.K., Qian, C., Marks, A.F., Slager, S.L., Peterson, B.J., et al. (2003). Mutations in CHEK2 associated with prostate cancer risk. Am J Hum Genet 72, 270–280.PubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Medicine, Division of Medical GeneticsSchool of Medicine, University of PennsylvaniaPhiladelphiaUSA

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