Risk Assessment & Genetic Testing

  • Pierre O. Chappuis
  • William D. Foulkes
Part of the Cancer Treatment and Research book series (CTAR, volume 107)


Ovarian cancer is the fifth most common cause of cancer death in women in Western countries and family history is one of the strongest known risk factors. Approximately 5 to 13% of all ovarian cancer cases are caused by the inheritance of cancer predisposing genes with an autosomal pattern of transmission. The inherited fraction of ovarian cancer may differ between populations. Based on analysis of familial ovarian cancer pedigrees and other epidemiological studies, three hereditary ovarian cancer syndromes have been defined. The identification of the genes responsible for most hereditary ovarian cancers has open a new area of early detection methods and preventive procedures specifically dedicated to women identified as carrying ovarian cancer predisposing genes. Predictive oncology is best performed by a dedicated unit with professionals aware of all the issues surrounding genetic testing.


Ovarian Cancer Epithelial Ovarian Cancer Ovarian Cancer Patient Founder Mutation Hereditary Nonpolyposis Colorectal 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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Hildreth NG, Kelsey JL, LiVolsi VA, et al. An epidemiologic study of epithelial carcinoma of the ovary. Am J Epidemiol 1981; 114: 398–405.PubMedGoogle Scholar
  2. 2.
    Parazzini F, Franceschi S, La Vecchia C, Fasoli M. The epidemiology of ovarian cancer. Gynecol Oncol 1991; 43: 9–23.PubMedCrossRefGoogle Scholar
  3. 3.
    Whittemore AS, Harris R, Itnyre J. Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. II. Invasive epithelial ovarian cancers in white women. Collaborative Ovarian Cancer Group. Am J Epidemiol 1992; 136: 1184–1203.PubMedGoogle Scholar
  4. 4.
    Amos CI, Struewing JP. Genetic epidemiology of epithelial ovarian cancer. Cancer 1993; 71: 566–72.PubMedCrossRefGoogle Scholar
  5. 5.
    Godard B, Foulkes WD, Provencher D, et al. Risk factors for familial and sporadic ovarian cancer among French Canadians: a case-control study. Am J Obstet Gynecol 1998; 179: 403–10.PubMedCrossRefGoogle Scholar
  6. 6.
    Cramer DW, Harlow BL, Willett WC, et al. Galactose consumption and metabolism in relation to the risk of ovarian cancer. Lancet 1989; 2: 66–71.PubMedCrossRefGoogle Scholar
  7. 7.
    Whittemore AS, Wu ML, Paffenbarger RS, Jr., et al. Personal and environmental characteristics related to epithelial ovarian cancer. II. Exposures to talcum powder, tobacco, alcohol, and coffee. Am J Epidemiol 1988; 128: 1228–40.PubMedGoogle Scholar
  8. 8.
    Mori M, Harabuchi I, Miyake H, et al. Reproductive, genetic, and dietary risk factors for ovarian cancer. Am J Epidemiol 1988; 128: 771–7.PubMedGoogle Scholar
  9. 9.
    Parazzini F, Negri E, La Vecchia C, et al. Family history of reproductive cancers and ovarian cancer risk: an Italian case-control study. Am J Epidemiol 1992; 135: 35–40.PubMedGoogle Scholar
  10. 10.
    Casagrande JT, Louie EW, Pike MC, Roy S, Ross RK, Henderson BE. “Incessant ovulation” and ovarian cancer. Lancet 1979; 2: 170–3.PubMedCrossRefGoogle Scholar
  11. 11.
    Cramer DW, Hutchison GB, Welch WR, et al. Determinants of ovarian cancer risk. I. Reproductive experiences and family history. J Natl Cancer Inst 1983; 71: 711–6.PubMedGoogle Scholar
  12. 12.
    Franceschi S, Parazzini F, Negri E, et al. Pooled analysis of 3 European case-control studies of epithelial ovarian cancer: III. Oral contraceptive use. Int J Cancer 1991; 49: 61–5.PubMedCrossRefGoogle Scholar
  13. 13.
    Hankinson SE, Hunter DJ, Colditz GA, et al. Tubal ligation, hysterectomy, and risk of ovarian cancer. A prospective study. JAMA 1993; 270: 2813–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Adami HO, Hsieh CC, Lambe M, et al. Parity, age at first childbirth, and risk of ovarian cancer. Lancet 1994; 344: 1250–4.PubMedCrossRefGoogle Scholar
  15. 15.
    Rosenberg L, Palmer JR, Zauber AG, et al. A case-control study of oral contraceptive use and invasive epithelial ovarian cancer. Am J Epidemiol 1994; 139: 654–61.PubMedGoogle Scholar
  16. 16.
    Kerber RA, Slattery ML. The impact of family history on ovarian cancer risk. The Utah Population Database. Arch Int Med 1995; 155: 905–12.CrossRefGoogle Scholar
  17. 17.
    Purdie D, Green A, Bain C, et al. Reproductive and other factors and risk of epithelial ovarian cancer: an Australian case-control study. Survey of Women’s Health Study Group. Int J Cancer 1995; 62: 678–84.PubMedCrossRefGoogle Scholar
  18. 18.
    Houlston RS, Collins A, Slack J, et al. Genetic epidemiology of ovarian cancer: segregation analysis. Ann Hum Genet 1991; 55: 291–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Narod SA, Madlensky L, Bradley L, et al. Hereditary and familial ovarian cancer in southern Ontario. Cancer 1994; 74: 2341–6.PubMedCrossRefGoogle Scholar
  20. 20.
    Narod SA, Ford D, Devilee P, et al. An evaluation of genetic heterogeneity in 145 breast-ovarian cancer families. Breast Cancer Linkage Consortium. Am J Hum Genet 1995; 56: 254–64.PubMedGoogle Scholar
  21. 21.
    Claus EB, Schildkraut JM, Thompson WD, Risch NJ. The genetic attributable risk of breast and ovarian cancer. Cancer 1996; 77: 2318–24.PubMedCrossRefGoogle Scholar
  22. 22.
    Whittemore AS, Gong G, Itnyre J. Prevalence and contribution of BRCA I mutations in breast cancer and ovarian cancer: results from three U.S. population-based case-control. studies of ovarian cancer. Am J Hum Genet 1997; 60: 496–504.PubMedGoogle Scholar
  23. 23.
    Muto MG, Cramer DW, Tangir J, et al. Frequency of the BRCAI 185delAG mutation among Jewish women with ovarian cancer and matched population controls. Cancer Res 1996; 56: 1250–2.PubMedGoogle Scholar
  24. 24.
    Modan B, Gak E, Sade-Bruchim RB, et al. High frequency of BRCAI 185delAG mutation in ovarian cancer in Israel. National Israel Study of Ovarian Cancer. JAMA 1996; 276: 1823–5.PubMedCrossRefGoogle Scholar
  25. 25.
    Gotlieb WH, Friedman E, Bar-Sade RB, et al. Rates of Jewish ancestral mutations in BRCA1 and BRCA2 in borderline ovarian tumors. J Natl Cancer Inst 1998; 90: 995 1000.Google Scholar
  26. 26.
    Moslehi R, Chu W, Karlan B, et al. BRCAI and BRCA2 mutation analysis of 208 Ashkenazi Jewish women with ovarian cancer. Am J Hum Genet 2000; 66: 1259–72.PubMedCrossRefGoogle Scholar
  27. 27.
    Claus EB, Schwartz PE. Familial ovarian cancer. Update and clinical applications. Cancer 1995; 76: 1998–2003.PubMedCrossRefGoogle Scholar
  28. 28.
    Parkin DM, Whelan SL, Ferlay J, Raymond L, Young J, editors. Cancer incidence in five continents vol. VII. Lyon: IARC Scientific Publications; 1997.Google Scholar
  29. 29.
    Greenlee RT, Murray T, Bolden S, Wingo PA. Cancer statistics, 2000. CA Cancer J Clin 2000; 50: 7–33.PubMedCrossRefGoogle Scholar
  30. 30.
    Hartge P, Whittemore AS, Itnyre J, and the collaborative ovarian cancer group. Rates and risks of ovarian cancer in subgroups of white women in the United States. Obstet Gynecol 1994; 84: 760–4.Google Scholar
  31. 31.
    Lynch HT, Lynch JF. Hereditary ovarian carcinoma. Hematol Oncol Clin North Am 1992; 6: 783–811.PubMedGoogle Scholar
  32. 32.
    Stratton JF, Pharoah P, Smith SK, et al. A systematic review and meta-analysis of family history and risk of ovarian cancer. Br J Obstet Gynaecol 1998; 105: 493–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Wynder EL, Dodo H, Barber HR. Epidemiology of cancer of the ovary. Cancer 1969; 23: 352–70.PubMedCrossRefGoogle Scholar
  34. 34.
    Tzonou A, Day NE, Trichopoulos D, et al. The epidemiology of ovarian cancer in Greece: a case-control study. Eur J Cancer Clin Oncol 1984; 20: 1045–52.PubMedCrossRefGoogle Scholar
  35. 35.
    Schildkraut JM, Thompson WD. Familial ovarian cancer: a population-based case- control study. Am J Epidemiol 1988; 128: 456–66.PubMedGoogle Scholar
  36. 36.
    Hartge P, Schiffman MH, Hoover R, et al. A case-control study of epithelial ovarian cancer. Am J Obstetr Gynecol 1989; 161: 10–6.Google Scholar
  37. 37.
    Koch M, Gaedke H, Jenkins H. Family history of ovarian cancer patients: a case- control study. Int J Epidemiol 1989; 18: 782–5.PubMedCrossRefGoogle Scholar
  38. 38.
    Goldgar DE, Easton DF, Cannon-Albright LA, Skolnick MH. Systematic population- based assessment of cancer risk in first-degree relatives of cancer probands. J Natl Cancer Inst 1994; 86: 1600–8.PubMedCrossRefGoogle Scholar
  39. 39.
    Auranen A, Pukkala E, Makinen J, et al. Cancer incidence in the first-degree relatives of ovarian cancer patients. Br J Cancer 1996; 74: 280–4.PubMedCrossRefGoogle Scholar
  40. 40.
    Easton DF, Matthews FE, Ford D, et al. Cancer mortality in relatives of women with ovarian cancer–the OPCS study. Int J Cancer 1996; 65: 284–94.PubMedCrossRefGoogle Scholar
  41. 41.
    Hemminki K, Vaittinen P, Kyyronen P. Age-specific familial risks in common cancers of the offspring. Int J Cancer 1998; 78: 172–5.PubMedCrossRefGoogle Scholar
  42. 42.
    Sutcliffe S, Pharoah PDP, Easton DF, Ponder BAJ. Ovarian and breast cancer risks to women in families with two or more cases of ovarian cancer. lnt J Cancer 2000; 87: 110–7.PubMedGoogle Scholar
  43. 43.
    Schildkraut JM, Risch N, Thompson WD. Evaluating genetic association among ovarian, breast, and endometrial cancer: evidence for a breast/ovarian cancer relationship. Am J Hum Genet 1989; 45: 521–9.PubMedGoogle Scholar
  44. 44.
    Greggi S, Genuardi M, Benedetti-Panici P, et al. Analysis of 138 consecutive ovarian cancer patients: incidence and characteristics of familial cases. Gynecol Oncol 1990; 39: 300–4.PubMedCrossRefGoogle Scholar
  45. 45.
    Amos CI, Shaw GL, Tucker MA, Hartge P. Age at onset for familial epithelial ovarian cancer. JAMA 1992; 268: 1896–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Houlston RS, Bourne TH, Collins WP, et al. Risk of ovarian cancer and genetic relationship to other cancers in families. Hum Hered 1993; 43: 111–5.PubMedCrossRefGoogle Scholar
  47. 47.
    Lynch HT, Watson P, Lynch JF, et al. Hereditary ovarian cancer. Heterogeneity in age at onset. Cancer 1993; 71: 573–81.PubMedCrossRefGoogle Scholar
  48. 48.
    Vaittinen P, Hemminki K. Familial cancer risks in offspring from discordant parental cancers. Int J Cancer 1999; 81: 12–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Jishi MF, Itnyre JH, Oakley-Girvan IA, et al. Risks of cancer among members of families in the Gilda Radner Familial Ovarian Cancer Registry. Cancer 1995; 76: 14 1621.Google Scholar
  50. 50.
    Auranen A, Grenman S, Makinen J, et al. Borderline ovarian tumors in Finland: epidemiology and familial occurrence. Am J Epidemiol 1996; 144: 548–53.PubMedCrossRefGoogle Scholar
  51. 51.
    Rader JS, Neuman RJ, Brady J, et al. Cancer among first-degree relatives of probands with invasive and borderline ovarian cancer. Obstet Gynecol 1998; 92: 589–95.PubMedCrossRefGoogle Scholar
  52. 52.
    Prior P, Waterhouse JA. Multiple primary cancers of the breast and ovary. Br J Cancer 1981; 44: 628–36.PubMedCrossRefGoogle Scholar
  53. 53.
    Schildkraut JM, Thompson WD. Relationship of epithelial ovarian cancer to other malignancies within families. Genet Epidemiol 1988; 5: 355–67.PubMedCrossRefGoogle Scholar
  54. 54.
    Tulinius H, Olafsdottir GH, Sigvaldason H, et al. Neoplastic diseases in families of breast cancer patients. J Med Genet 1994; 31: 618–21.PubMedCrossRefGoogle Scholar
  55. 55.
    Olsen JH, Seersholm N, Boice JDJ, et al. Cancer risk in close relatives of women with early-onset breast cancer-a population-based incidence study. Br J Cancer 1999; 79: 673–9.PubMedCrossRefGoogle Scholar
  56. 56.
    Auranen A, Iselius L. Segregation analysis of epithelial ovarian cancer in Finland. Br J Cancer 1998; 77: 1537–41.PubMedCrossRefGoogle Scholar
  57. 57.
    Kasprzak L, Foulkes WD, Shelling AN. Forthnightly review: hereditary ovarian carcinoma. BMJ. 1999; 318: 786–9.PubMedCrossRefGoogle Scholar
  58. 58.
    Liber AF. Ovarian cancer in a mother and five daughters. Arch Pathol 1950; 49: 280–90.Google Scholar
  59. 59.
    Go RC, King MC, Bailey-Wilson J, et al. Genetic epidemiology of breast cancer and associated cancers in high-risk families. I. Segregation analysis. J Natl Cancer Inst 1983; 71: 455–61.PubMedGoogle Scholar
  60. 60.
    Hall JM, Lee MK, Newman B, et al. Linkage of early-onset familial breast cancer to chromosome 17g21. Science 1990; 250: 1684–9.PubMedCrossRefGoogle Scholar
  61. 61.
    Narod SA, Feunteun J, Lynch HT, et al. Familial breast-ovarian cancer locus on chromosome 17g12-q23. Lancet 1991; 338: 82–3.PubMedCrossRefGoogle Scholar
  62. 62.
    Miki Y, Swensen J, Shattuck-Eidens D, et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCAI. Science 1994; 266: 66–71.PubMedCrossRefGoogle Scholar
  63. 63.
    Wooster R, Neuhausen SL, Mangion J, et al. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12–13. Science 1994; 265: 2088–90.PubMedCrossRefGoogle Scholar
  64. 64.
    Wooster R, Bignell G, Lancaster J, et al. Identification of the breast cancer susceptibility gene BRCA2. Nature 1995; 378: 789–92.PubMedCrossRefGoogle Scholar
  65. 65.
    Easton DF, Bishop DT, Ford D, Crockford GP. Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium. Am J Hum Genet 1993; 52: 678–701.PubMedGoogle Scholar
  66. 66.
    Ford D, Easton DF, Stratton M, et al. Genetic heterogeneity and penetrance analysis of the BRCAI and BRCA2 genes in breast cancer families. Am J Hum Genet 1998; 62: 676–89.PubMedCrossRefGoogle Scholar
  67. 67.
    Frank TS, Manley SA, Olopade 01, et al. Sequence analysis of BRCAI and BRCA2: correlation of mutations with family history and ovarian cancer risk. J Clin Oncol 1998; 16: 2417–25.PubMedGoogle Scholar
  68. 68.
    Tonin P, Weber B, Offit K, et al. Frequency of recurrent BRCA 1 and BRCA2 mutations in Ashkenazi Jewish breast cancer families. Nat Med 1996; 2: 1183–96.CrossRefGoogle Scholar
  69. 69.
    Ligtenberg MJ, Hogervorst FB, Willems HW, et al. Characteristics of small breast and/or ovarian cancer families with germline mutations in BRCAI and BRCA2. Br J Cancer 1999; 79: 1475–8.PubMedCrossRefGoogle Scholar
  70. 70.
    Stratton JF, Gayther SA, Russell P, et al. Contribution of BRCAI mutations to ovarian cancer. N Engl J Med 1997; 336: 1125–30.PubMedCrossRefGoogle Scholar
  71. 71.
    Ford D, Easton DF, Peto J. Estimates of the gene frequency of BRCAI and its contribution to breast and ovarian cancer incidence. Am J Hum Genet 1995; 57: 145762.Google Scholar
  72. 72.
    Gayther SA, Mangion J, Russell P, et al. Variation of risks of breast and ovarian cancer associated with different germline mutations of the BRCA2 gene. Nat Genet 1997; 15: 103–5.PubMedCrossRefGoogle Scholar
  73. 73.
    Karlan BY, Baldwin RL, Lopez-Luevanos E, et al. Peritoneal serous papillary carcinoma, a phenotypic variant of familial ovarian cancer: implications for ovarian cancer screening. Am J Obstet Gynecol 1999; 180: 917–28.PubMedCrossRefGoogle Scholar
  74. 74.
    Ford D, Easton DF, Bishop DT, et al. Risks of cancer in BRCAI-mutation carriers. Breast Cancer Linkage Consortium. Lancet 1994; 343: 692–5.PubMedCrossRefGoogle Scholar
  75. 75.
    Antoniou AC, Gayther SA, Stratton JF, et al. Risk models for familial ovarian and breast cancer. Genet Epidemiol 2000; 18: 173–90.PubMedCrossRefGoogle Scholar
  76. 76.
    Richards WE, Gallion HH, Schmittschmitt JP, et al. BRCAI-related and sporadic ovarian cancer in the same family: implications for genetic testing. Gynecol Oncol 1999; 75: 468–72.PubMedCrossRefGoogle Scholar
  77. 77.
    Easton DF, Ford D, Bishop DT. Breast and ovarian cancer incidence in BRCA1mutation carriers. Breast Cancer Linkage Consortium. Am J Hum Genet 1995; 56: 26571.Google Scholar
  78. 78.
    Abeliovich D, Kaduri L, Lerer I, et al. The founder mutations I85delAG and 5382insC in BRCA 1 and 6174delT in BRCA2 appear in 60-percent of ovarian cancer and 30-percent of early-onset breast cancer patients among Ashkenazi women. Am J Hum Genet 1997; 60: 505–14.PubMedGoogle Scholar
  79. 79.
    Easton DF, Steele L, Fields P, et al. Cancer risks in two large breast cancer families linked to BRCA2 on chromosome 13q12–13. Am J Hum Genet 1997; 61: 120–8.PubMedCrossRefGoogle Scholar
  80. 80.
    Levy-Lahad E, Catane R, Eisenberg S, et al. Founder BRCAI and BRCA2 mutations in Ashkenazi Jews in Israel: frequency and differential penetrance in ovarian cancer and in breast-ovarian cancer families. Am J Hum Genet 1997; 60: 1059–67.PubMedGoogle Scholar
  81. 81.
    Struewing JP, Hartge P, Wacholder S, et al. The risk of cancer associated with specific mutations of BRCA 1 and BRCA2 among Ashkenazi Jews. N Engl J Med 1997; 336: 1401–8.PubMedCrossRefGoogle Scholar
  82. 82.
    Warner E, Foulkes W, Goodwin P, et al. Prevalence and penetrance of BRCAI and BRCA2 gene mutations in unselected Ashkenazi Jewish women with breast cancer. J Natl Cancer Inst 1999; 91: 1241–7.PubMedCrossRefGoogle Scholar
  83. 83.
    Steichen-Gersdorf E, Gallion HH, Ford D, et al. Familial site-specific ovarian cancer is linked to BRCA I on 17q12–21. Am J Hum Genet 1994; 55: 870–5.PubMedGoogle Scholar
  84. 84.
    Shattuck-Eidens D, McClure M, Simard J, et al. A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene. Implications for presymptomatic testing and screening. JAMA 1995; 273: 535–41.PubMedCrossRefGoogle Scholar
  85. 85.
    Roth S, Kristo P, Auranen A, et al. A missense mutation in the BRCA2 gene in three siblings with ovarian cancer. Br J Cancer 1998; 77: 1199–202.PubMedCrossRefGoogle Scholar
  86. 86.
    Liede A, Tonin PN, Sun CC, et al. Is hereditary site-specific ovarian cancer a distinct genetic condition? Am J Med Genet 1998; 75: 55–8.PubMedCrossRefGoogle Scholar
  87. 87.
    Gayther SA, Russell P, Harrington P, et al. The contribution of germline BRCA1 and BRCA2 mutations to familial ovarian cancer: No evidence for other ovarian cancer-susceptibility genes. Am J Hum Genet 1999; 65: 1021–9.PubMedCrossRefGoogle Scholar
  88. 88.
    Santarosa M, Dolcetti R, Magri MD, et al. BRCA1 and BRCA2 genes: role in hereditary breast and ovarian cancer in Italy. Int J Cancer 1999; 83: 5–9.PubMedCrossRefGoogle Scholar
  89. 89.
    Lynch HT, de la Chapelle A. Genetic susceptibility to non-polyposis colorectal cancer. J Med Genet 1999; 36: 801–18.PubMedGoogle Scholar
  90. 90.
    Vasen HF, Mecklin JP, Khan PM, Lynch HT. The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC). Dis Colon Rectum 1991; 34: 424–5.PubMedCrossRefGoogle Scholar
  91. 91.
    Vasen HF, Watson P, Mecklin JP, Lynch HT. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology 1999; 116: 1453–6.PubMedCrossRefGoogle Scholar
  92. 92.
    Ichikawa Y, Lemon SJ, Wang S, et al. Microsatellite instability and expression of MLH1 and MSH2 in normal and malignant endometrial and ovarian epithelium in hereditary nonpolyposis colorectal cancer family members. Cancer Genet Cytogenet 1999; 112: 2–8.PubMedCrossRefGoogle Scholar
  93. 93.
    Fujita M, Enomoto T, Yoshino K, et al. Microsatellite instability and alterations in the hMSH2 gene in human ovarian cancer. Int J Cancer 1995; 64: 361–6.PubMedCrossRefGoogle Scholar
  94. 94.
    Arzimanoglou II, Lallas T, Osborne M, et al. Microsatellite instability differences between familial and sporadic ovarian cancers. Carcinogenesis 1996; 17: 1799–804.PubMedCrossRefGoogle Scholar
  95. 95.
    Allen HJ, DiCioccio RA, Hohmann P, et al. Microsatellite instability in ovarian and other pelvic carcinomas. Cancer Genet Cytogenet 2000; 117: 163–6.PubMedCrossRefGoogle Scholar
  96. 96.
    Vasen HF, Wijnen JT, Menko FH, et al. Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterology 1996; 110: 1020–7.PubMedCrossRefGoogle Scholar
  97. 97.
    Lin KM, Shashidharan M, Ternent CA, et al. Colorectal and extracolonic cancer variations in MLHIIMSH2 hereditary nonpolyposis colorectal cancer kindreds and the general population. Dis Colon Rectum 1998; 41: 428–33.PubMedCrossRefGoogle Scholar
  98. 98.
    Aarnio M, Sankila R, Pukkala E, et al. Cancer risk in mutation carriers of DNAmismatch-repair genes. Int J Cancer 1999; 81: 214–8.PubMedCrossRefGoogle Scholar
  99. 99.
    Froggatt NJ, Green J, Brassett C, et al. A common MSH2 mutation in English and North American HNPCC families: origin, phenotypic expression, and sex specific differences in colorectal cancer. J Med Genet 1999; 36: 97–102.PubMedGoogle Scholar
  100. 100.
    Wijnen JT, Vasen HF, Khan PM, et al. Clinical findings with implications for genetic testing in families with clustering of colorectal cancer. N Engl J Med 1998; 339: 511–8.PubMedCrossRefGoogle Scholar
  101. 101.
    Rubin SC, Blackwood MA, Bandera C, et al. BRCA1, BRCA2, and hereditary nonpolyposis colorectal cancer gene mutations in an unselected ovarian cancer population: relationship to family history and implications for genetic testing. Am J Obstet Gynecol 1998; 178: 670–7.PubMedCrossRefGoogle Scholar
  102. 102.
    Watson P, Lynch HT. Extracolonic cancer in hereditary nonpolyposis colorectal cancer. Cancer 1993; 71: 677–85.PubMedCrossRefGoogle Scholar
  103. 103.
    Stratton JF, Thompson D, Bobrow L, et al. The genetic epidemiology of early-onset epithelial ovarian cancer: a population-based study. Am J Hum Genet 1999; 65: 17 2532.Google Scholar
  104. 104.
    Borresen AL. Oncogenesis in ovarian cancer. Acta Obstet Gynecol Scand 1992; 71 Suppl 155: 25–30.Google Scholar
  105. 105.
    Jolly KW, Malkin D, Douglass EC, et al. Splice-site mutation of the p53 gene in a family with hereditary breast-ovarian cancer. Oncogene 1994; 9: 97–102.PubMedGoogle Scholar
  106. 106.
    Buller RE, Skilling JS, Kaliszewski S, et al. Absence of significant germ line p53 mutations in ovarian cancer patients. Gynecol Oncol 1995; 58: 368–74.PubMedCrossRefGoogle Scholar
  107. 107.
    Kleihues P, Schauble B, zur Hausen, et al. Tumors associated with p53 germline mutations: a synopsis of 91 families. Am J Pathol 1997; 150: 1–13.Google Scholar
  108. 108.
    Birch JM, Blair V, Kelsey AM, et al. Cancer phenotype correlates with constitutional TP53 genotype in families with the Li-Fraumeni syndrome. Oncogene 1998; 17: 10618.CrossRefGoogle Scholar
  109. 109.
    Stettner AR, Hartenbach EM, Schink JC, et al. Familial ovarian germ cell cancer: report and review. Am J Med Genet 1999; 84: 43–6.PubMedCrossRefGoogle Scholar
  110. 110.
    Bewtra C, Watson P, Conway T, et al. Hereditary ovarian cancer: a clinicopathological study. Int J Gynecol Pathol 1992; 11: 180–7.PubMedCrossRefGoogle Scholar
  111. 111.
    Piver MS, Baker TR, Jishi MF, et al. Familial ovarian cancer. A report of 658 families from the Gilda Radner Familial Ovarian Cancer Registry 1981–1991. Cancer 1993; 71: 582–8.PubMedCrossRefGoogle Scholar
  112. 112.
    Rubin SC, Benjamin I, Behbakht K, et al. Clinical and pathoological features of ovarian cancer in women with germ-line mutations of BRCAI. N Engl J Med 1996; 335: 14136.Google Scholar
  113. 113.
    Zweemer RP, Verheijen RH, Gille JJ, et al. Clinical and genetic evaluation of thirty ovarian cancer families. Am J Obstet Gynecol 1998; 178: 85–90.PubMedCrossRefGoogle Scholar
  114. 114.
    Boyd J, Sonoda Y, Federici MG, et al. Clinicopathologic features of BRCA-linked and sporadic ovarian cancer. JAMA 2000; 283: 2260–5.PubMedCrossRefGoogle Scholar
  115. 115.
    Chang J, Fryatt I, Ponder B, et al. A matched control study of familial epithelial ovarian cancer: patient characteristics, response to chemotherapy and outcome. Ann Oncol 1995; 6: 80–2.PubMedGoogle Scholar
  116. 116.
    Auranen A, Grenman S, Kleml PJ. Immunohistochemically detected p53 and HER2/neu expression and nuclear DNA content in familial epithelial ovarian carcinomas. Cancer 1997; 79: 2147–53.PubMedCrossRefGoogle Scholar
  117. 117.
    Johannsson OT, Ranstam J, Borg A, Olsson H. Survival of BRCA I Breast and Ovarian Cancer Patients: A Population-Based Study From Southern Sweden. J Clin Oncol 1998; 16: 397–404.PubMedGoogle Scholar
  118. 118.
    Yamashita Y, Sagawa T, Fujimoto T, et al. BRCAI mutation testing for Japanese patients with ovarian cancer in breast cancer screening. Breast Cancer Res Treat 1999; 58: 11–7.PubMedCrossRefGoogle Scholar
  119. 119.
    Takahashi H, Chiu HC, Bandera CA, et al. Mutations of the BRCA2 gene in ovarian carcinomas. Cancer Res 1996; 56: 2738–41.PubMedGoogle Scholar
  120. 120.
    Tonin PM, Mes-Masson AM, Narod SA, et al. Founder BRCA1 and BRCA2 mutations in French Canadian ovarian cancer cases unselected for family history. Clin Genet 1999; 55: 318–24.PubMedCrossRefGoogle Scholar
  121. 121.
    Scully RE. Influence of origin of ovarian cancer on efficacy of screening. Lancet 2000; 355: 1028–9.PubMedCrossRefGoogle Scholar
  122. 122.
    Salazar H, Godwin AK, Daly MB, et al. Microscopic benign and invasive malignant neoplasms and a cancer-prone phenotype in prophylactic oophorectomies. J Natl Cancer Inst 1996; 88: 1810–20.PubMedCrossRefGoogle Scholar
  123. 123.
    Deligdisch L, Gil J, Kerner H, et al. Ovarian dysplasia in prophylactic oophorectomy specimens: cytogenetic and morphometric correlations. Cancer 1999; 86: 1544–50.PubMedCrossRefGoogle Scholar
  124. 124.
    Stratton JF, Buckley CH, Lowe D, Ponder BA. Comparison of prophylactic oophorectomy specimens from carriers and noncarriers of a BRCA1 or BRCA2 gene mutation. J Natl Cancer Inst 1999; 91: 626–8.PubMedCrossRefGoogle Scholar
  125. 125.
    Werness BA, Afify AM, Bielat KL, et al. Altered surface and cyst epithelium of ovaries removed prophylactically from women with a family history of ovarian cancer. Hum Pathol 1999; 30: 151–7.PubMedCrossRefGoogle Scholar
  126. 126.
    Narod SA, Tonin P, Lynch H, et al. Histology of BRCA I -associated ovarian tumours. Lancet 1994; 343: 236.PubMedCrossRefGoogle Scholar
  127. 127.
    Matsushima M, Kobayashi K, Emi M, et al. Mutation analysis of the BRCAI gene in 76 Japanese ovarian cancer patients: four germline mutations, but no evidence of somatic mutation. Hum Mol Genet 1995; 4: 1953–6.PubMedCrossRefGoogle Scholar
  128. 128.
    Takahashi H, Behbakht K, McGovern PE, et al. Mutation analysis of the BRCAI gene in ovarian cancers. Cancer Res 1995; 55: 2998–3002.PubMedGoogle Scholar
  129. 129.
    Takano M, Aida H, Tsuneki I, et al. Mutational analysis of BRCA 1 gene in ovarian and breast-ovarian cancer families in Japan. Jpn J Cancer Res 1997; 88: 407–13.PubMedCrossRefGoogle Scholar
  130. 130.
    Aida H, Takakuwa K, Nagata H, et al. Clinical features of ovarian cancer in Japanese women with germ-line mutations of BRCAI. Clin Cancer Res 1998; 4: 235–40.PubMedGoogle Scholar
  131. 131.
    Berchuck A, Heron KA, Carney ME, et al. Frequency of germline and somatic BRCAI mutations in ovarian cancer. Clin Cancer Res 1998; 4: 2433–7.PubMedGoogle Scholar
  132. 132.
    Pharoah PD, Easton DF, Stockton DL, et al. Survival in familial, BRCAI-associated, and BRCA2-associated epithelial ovarian cancer. United Kingdom Coordinating Committee for Cancer Research (UKCCCR) Familial Ovarian Cancer Study Group. Cancer Res 1999; 59: 868–71.PubMedGoogle Scholar
  133. 133.
    Sagawa T, Yamashita Y, Fujimoto T, et al. Clinicopathological comparisons of familial and sporadic cases in 219 consecutive Japanese epithelial ovarian cancer patients. Jpn J Clin Oncol 1999; 29: 556–61.PubMedCrossRefGoogle Scholar
  134. 134.
    Johannsson OT, Idvall I, Anderson C, et al. Tumour biological features of BRCA1induced breast and ovarian cancer. Eur J Cancer 1997; 33: 362–71.PubMedCrossRefGoogle Scholar
  135. 135.
    Levy-Lahad E, Kaufman B, Eisenberg S, et al. Differential ovarian cancer survival in Ashkenazi BRCA1/BRCA2 carriers [abstract]. Am J Hum Genet 1999; 65 Supp1:135.Google Scholar
  136. 136.
    Lu KH, Cramer DW, Muto MG, et ai. A population-based study of BRCAI and BRCA2 mutations in Jewish women with epithelial ovarian cancer. Obstet Gynecol 1999; 93: 34–7.PubMedCrossRefGoogle Scholar
  137. 137.
    Lamovec J, Bracko M, Cerar O. Familial occurrence of small-cell carcinoma of the ovary. Arch Pathol Lab Med 1995; 119: 523–7.PubMedGoogle Scholar
  138. 138.
    Longy M, Toulouse C, Mage P, et al. Familial cluster of ovarian small cell carcinoma: a new mendelian entity? J Med Genet 1996; 33: 333–5.PubMedCrossRefGoogle Scholar
  139. 139.
    Buller RE, Anderson B, Connor JP, Robinson R. Familial ovarian cancer. Gynecol Oncol 1993; 51: 160–6.PubMedCrossRefGoogle Scholar
  140. 140.
    Piver MS, Jishi MF, Tsukada Y, Nava G. Primary peritoneal carcinoma after prophylactic oophorectomy in women with a family history of ovarian cancer. A report of the Gilda Radner Familial Ovarian Cancer Registry. Cancer 1993; 71: 2751–5.PubMedCrossRefGoogle Scholar
  141. 141.
    Struewing JP, Watson P, Easton DF, et al. Prophylactic oophorectomy in inherited breast/ovarian cancer families. J Natl Cancer Inst Monograph 1995; 33–5.Google Scholar
  142. 142.
    Bandera CA, Muto MG, Schorge JO, et al. BRCAI gene mutations in women with papillary serous carcinoma of the peritoneum. Obstet Gynecol 1998; 92: 596–600.PubMedCrossRefGoogle Scholar
  143. 143.
    Berchuck A, Schildkraut JM, Marks JR, Futreal PA. Managing hereditary ovarian cancer risk. Cancer 1999; 86: 1697–704.CrossRefGoogle Scholar
  144. 144.
    Fathalla MF. Incessant ovulation-a factor in ovarian neoplasia?. Lancet 1971; 2: 163.PubMedCrossRefGoogle Scholar
  145. 145.
    Eisen A, Weber BL. Primary peritoneal carcinoma can have multifocal origins: implications for prophylactic oophorectomy. J Natl Cancer Inst 1998; 90: 797–9.PubMedCrossRefGoogle Scholar
  146. 146.
    Schorge JO, Muto MG, Welch WR, et al. Molecular evidence for multifocal papillary serous carcinoma of the peritoneum in patients with germline BRCAI mutations. J Natl Cancer Inst 1998; 90: 841–5.PubMedCrossRefGoogle Scholar
  147. 147.
    Schorge JO, Muto MG, Lee SJ, et al. BRCAI-related papillary serous carcinoma of the peritoneum has a unique molecular pathogenesis. Cancer Res 2000; 60: 1361–4.PubMedGoogle Scholar
  148. 148.
    Struewing JP, Coriaty ZM, Ron E, et al. Founder BRCA1/2 mutations among male patients with breast cancer in Israel. Am J Hum Genet 1999; 65: 1800–2.PubMedCrossRefGoogle Scholar
  149. 149.
    Csokay B, Udvarhelyi N, Sulyok Z, et al. High frequency of germ-line BRCA2 mutations among Hungarian male breast cancer patients without family history. Cancer Res 1999; 59: 995–8.PubMedGoogle Scholar
  150. 150.
    Haraldsson K, Loman N, Zhang QX, et al. BRCA2 germ-line mutations are frequent in male breast cancer patients without a family history of the disease. Cancer Res 1998; 58: 1367–71.PubMedGoogle Scholar
  151. 151.
    Douglas FS, O’Dair LC, Robinson M, et al. The accuracy of diagnoses as reported in families with cancer: a retrospective study. J Med Genet 1999; 36: 309–12.PubMedGoogle Scholar
  152. 152.
    Ottman R, Pike MC, King MC, Henderson BE. Practical guide for estimating risk for familial breast cancer. Lancet 1983; 2: 556–8.PubMedCrossRefGoogle Scholar
  153. 153.
    Anderson DE, Badzioch MD. Risk of familial breast cancer. Cancer 1985; 56: 383–7.PubMedCrossRefGoogle Scholar
  154. 154.
    Claus EB, Risch N, Thompson WD. Autosomal dominant inheritance of early-onset breast cancer. Implications for risk prediction. Cancer 1994; 73: 643–51.PubMedCrossRefGoogle Scholar
  155. 155.
    Gail MH, Brinton LA, Byar DP, et al. Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst 1989; 81: 1879–86.PubMedCrossRefGoogle Scholar
  156. 156.
    Weitzel JN. Genetic cancer risk assessment: putting it all together. Cancer 1999; 86: 1663–72.CrossRefGoogle Scholar
  157. 157.
    Couch FJ, DeShano ML, Blackwood MA, et al. BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer. N Engl J Med 1997; 336: 1409–15.PubMedCrossRefGoogle Scholar
  158. 158.
    Parmigiani G, Berry D, Aguilar O. Determining carrier probabilities for breast cancer-susceptibility genes BRCA1 and BRCA2. Am J Hum Genet 1998; 62: 145–58.PubMedCrossRefGoogle Scholar
  159. 159.
    Statement of the American Society of Clinical Oncology: genetic testing for cancer susceptibility. J Clin Oncol 1996; 14:1730–6.Google Scholar
  160. 160.
    Foster KA, Harrington P, Kerr J, et al. Somatic and germline mutations of the BRCA2 gene in sporadic ovarian cancer. Cancer Res 1996; 56: 3622–5.PubMedGoogle Scholar
  161. 161.
    Johannesdottir G, Gudmundsson J, Bergthorsson JT, et al. High prevalence of the 999del5 mutation in Icelandic breast and ovarian cancer patients. Cancer Res 1996; 56: 3663–5.PubMedGoogle Scholar
  162. 162.
    Lancaster JM, Wooster R, Mangion J, et al. BRCA2 mutations in primary breast and ovarian cancers. Nat Genet 1996; 13: 238–40.PubMedCrossRefGoogle Scholar
  163. 163.
    Dorum A, Hovig E, Trope C, et al. Three per cent of Norwegian ovarian cancers are caused by BRCAI 1675delA or 1135insA. Eur J Cancer 1999; 35: 779–81.PubMedCrossRefGoogle Scholar
  164. 164.
    Janezic SA, Ziogas A, Krumroy LM, et al. Germline BRCA1 alterations in a population-based series of ovarian cancer cases. Hum Mol Genet 1999; 8: 889–97.PubMedCrossRefGoogle Scholar
  165. 165.
    Van der Looij M, Szabo C, Besznyak I, et al. Prevalence of founder BRCA1 and BRCA2 mutations among breast and ovarian cancer patients in Hungary. Int J Cancer 2000; 86: 737–40.CrossRefGoogle Scholar
  166. 166.
    Beller U, Halle D, Catane R, et al. High frequency of BRCA1 and BRCA2 germline mutations in Ashkenazi Jewish ovarian cancer patients, regardless of family history. Gynecol Oncol 1997; 67: 123–6.PubMedCrossRefGoogle Scholar
  167. 167.
    Hodgson SV, Heap E, Cameron J, et al. Risk factors for detecting germline BRCA1 and BRCA2 founder mutations in Ashkenazi Jewish women with breast or ovarian cancer. J Med Genet 1999; 36: 369–73.PubMedGoogle Scholar
  168. 168.
    Frank TS. Laboratory identification of hereditary risk of breast and ovarian cancer. Curr Opin Biotechnol 1999; 10: 289–94.PubMedCrossRefGoogle Scholar
  169. 169.
    Welcsh PL, Owens KN, King MC. Insights into the functions of BRCA1 and BRCA2. Trends Genet 2000; 16: 69–74.PubMedCrossRefGoogle Scholar
  170. 170.
    Haber D. BRCA1: an emerging role in the cellular response to DNA damage. Lancet 2000; 355: 2090–1.PubMedCrossRefGoogle Scholar
  171. 171.
    Struewing JP, Abeliovich D, Peretz T, et al. The carrier frequency of the BRCA I 185delAG mutation is approximately 1 percent in Ashkenazi Jewish individuals. Nat Genet 1995; 11: 198–200.PubMedCrossRefGoogle Scholar
  172. 172.
    Oddoux C, Struewing JP, Clayton CM, et al. The carrier frequency of the BRCA2 6174delT mutation among Ashkenazi Jewish individuals is approximately 1 percent. Nat Genet 1996; 14: 188–90.PubMedCrossRefGoogle Scholar
  173. 173.
    Roa BB, Boyd AA, Volcik K, Richards CS. Ashkenazi Jewish population frequencies for common mutations in BRCAI and BRCA2. Nat Genet 1996; 14: 185–7.PubMedCrossRefGoogle Scholar
  174. 174.
    Tesoriero A, Andersen C, Southey M, et al. De novo BRCAI mutation in a patient with breast cancer and an inherited BRCA2 mutation. Am J Hum Genet 1999; 65: 567–9.PubMedCrossRefGoogle Scholar
  175. 175.
    Shattuck-Eidens D, Oliphant A, McClure M, et al. BRCA 1 sequence analysis in women at high risk for susceptibility mutations-risk factor analysis and implications for genetic testing. JAMA 1997; 278: 1242–50.PubMedCrossRefGoogle Scholar
  176. 176.
    Hogervorst FB, Cornelis RS, Bout M, et al. Rapid detection of BRCA1 mutations by the protein truncation test. Nat Genet 1995; 10: 208–12.PubMedCrossRefGoogle Scholar
  177. 177.
    Petrij-Bosch A, Peelen T, van Vliet M, et al. BRCAI genomic deletions are major founder mutations in Dutch breast cancer patients. Nat Genet 1997; 17: 341–5.PubMedCrossRefGoogle Scholar
  178. 178.
    Swensen J, Hoffman M, Skolnick MH, Neuhausen SL. Identification of a 14 kb deletion involving the promoter region of BRCAI in a breast cancer family. Hum Mol Genet 1997; 6: 1513–7.PubMedCrossRefGoogle Scholar
  179. 179.
    Montagna M, Santacatterina M, Torri A, et al. Identification of a 3 kb Alu-mediated BRCAI gene rearrangement in two breast/ovarian cancer families. Oncogene 1999; 18: 4160–5.PubMedCrossRefGoogle Scholar
  180. 180.
    Puget N, Stoppa-Lyonnet D, Sinilnikova OM, et al. Screening for germ-line rearrangements and regulatory mutations in BRCA I led to the identification of four new deletions. Cancer Res 1999; 59: 455–61.PubMedGoogle Scholar
  181. 181.
    Gayther SA, Warren W, Mazoyer S, et al. Germline mutations of the BRCAI gene in breast and ovarian cancer families provide evidence for a genotype-phenotype correlation. Nat Genet 1995; 11: 428–33.PubMedCrossRefGoogle Scholar
  182. 182.
    Phelan CM, Rebbeck TR, Weber BL, et al. Ovarian cancer risk in BRCAI carriers is modified by the HRASI variable number of tandem repeat (VNTR) locus. Nat Genet 1996; 12: 309–11.PubMedCrossRefGoogle Scholar
  183. 183.
    Stoppa-Lyonnet D, Laurent-Puig P, Essioux L, et al. BRCAI sequence variations in 160 individuals referred to a breast/ovarian family cancer clinic. Institut Curie Breast Cancer Group. Am J Hum Genet 1997; 60: 1021–30.PubMedGoogle Scholar
  184. 184.
    Thompson DJ, Easton DF, Breast Cancer Linkage Consortium. Evidence for genotype-phenotype correlations in BRCA2 [abstract]. Am J Hum Genet 1999; 65 Suppl:327.Google Scholar
  185. 185.
    van Orsouw NJ, Dhanda RK, Elhaji Y, et al. A highly accurate, low cost test for BRCAI mutations. J Med Genet 1999; 36: 747–53.PubMedGoogle Scholar
  186. 186.
    Wagner T, Stoppa-Lyonnet D, Fleischmann E, et al. Denaturing high-performance liquid chromatography detects reliably BRCA1 and BRCA2 mutations. Genomics 1999; 62: 369–76.PubMedCrossRefGoogle Scholar
  187. 187.
    Humphrey JS, Salim A, Erdos MR, et al. Human BRCA I inhibits growth in yeast: potential use in diagnostic testing. Proc Natl Acad Sci USA 1997; 94: 5820–5.PubMedCrossRefGoogle Scholar
  188. 188.
    Hacia JG, Brody LC, Chee MS, et al. Detection of heterozygous mutations in BRCA1 using high density oligonucleotide arrays and two-colour fluorescence analysis. Nat Genet 1996; 14: 441–7.PubMedCrossRefGoogle Scholar
  189. 189.
    Rothfuss A, Schutz P, Bochum S, et al. Induced micronucleus frequencies in peripheral lymphocytes as a screening test for carriers of a BRCAI mutation in breast cancer families. Cancer Res 2000; 60: 390–4.PubMedGoogle Scholar
  190. 190.
    Wijnen J, de Leeuw W, Vasen H, et al. Familial endometrial cancer in female carriers of MSH6 germline mutations. Nat Genet 1999; 23: 142–4.PubMedCrossRefGoogle Scholar
  191. 191.
    Wu Y, Berends MJ, Mensink RG, et al. Association of hereditary nonpolyposis colorectal cancer-related tumors displaying low microsatellite instability with MSH6 germline mutations. Am J Hum Genet 1999; 65: 1291–8.PubMedCrossRefGoogle Scholar
  192. 192.
    Andreutti-Zaugg C, Scott RJ, Iggo R. Inhibition of nonsense-mediated messenger RNA decay in clinical samples facilitates detection of human MSH2 mutations with an in vivo fusion protein assay and conventional techniques. Cancer Res 1997; 57: 3288–93.PubMedGoogle Scholar
  193. 193.
    Shimodaira H, Filosi N, Shibata H, et al. Functional analysis of human MLH1 mutations in Saccharomyces cerevisiae. Nat Genet 1998; 19: 384–9.PubMedCrossRefGoogle Scholar
  194. 194.
    Polaczek P, Putzke AP, Leong K, Bitter GA. Functional genetic tests of DNA mismatch repair protein activity in Saccharomyces cerevisiae. Gene 1998; 213: 159–67.PubMedCrossRefGoogle Scholar
  195. 195.
    Johannsson O, Ostermeyer EA, Hakansson S, et al. Founding BRCAI mutations in hereditary breast and ovarian cancer in southern Sweden. Am J Hum Genet 1996; 58: 441–50.PubMedGoogle Scholar
  196. 196.
    Andersen TI, Borresen AL, Moller P. A common BRCA1 mutation in Norwegian breast and ovarian cancer families?. Am J Hum Genet 1996; 59: 486–7.PubMedGoogle Scholar
  197. 197.
    Wagner TM, Moslinger R, Zielinski C, et al. New Austrian mutation in BRCA I gene detected in three unrelated HBOC families. Lancet 1996; 347: 1263.PubMedCrossRefGoogle Scholar
  198. 198.
    Dorum A, Moller P, Kamsteeg EJ, et al. A BRCAI founder mutation, identified with haplotype analysis, allowing genotype/phenotype determination and predictive testing. Eur J Cancer 1997; 33: 2390–2.PubMedCrossRefGoogle Scholar
  199. 199.
    Peelen T, van Vliet M, Petrij-Bosch A, et al. A high proportion of novel mutations in BRCA I with strong founder effects among Dutch and Belgian hereditary breast and ovarian cancer families. Am J Hum Genet 1997; 60: 1041–9.PubMedGoogle Scholar
  200. 200.
    Gayther SA, Harrington P, Russell P, et al. Frequently occurring germ-line mutations of the BRCA1 gene in ovarian cancer families from Russia. Am J Hum Genet 1997; 60: 1239–42.PubMedGoogle Scholar
  201. 201.
    Ramus SJ, Kote-Jarai Z, Friedman LS, et al. Analysis of BRCA1 and BRCA2 mutations in Hungarian families with breast or breast-ovarian cancer. Am J Hum Genet 1997; 60: 1242–6.PubMedGoogle Scholar
  202. 202.
    Tonin PN, Mes-Masson A-M, Futreal PA, et al. Founder BRCAI and BRCA2 mutations in French Canadian breast and ovarian cancer families. Am J Hum Genet 1998; 63: 1341–51.PubMedCrossRefGoogle Scholar
  203. 203.
    Friedman LS, Szabo CI, Ostermeyer EA, et al. Novel inherited mutations and variable expressivity of BRCAI alleles, including the founder mutation 185delAG in Ashkenazi Jewish families. Am J Hum Genet 1995; 57: 1284–97.PubMedGoogle Scholar
  204. 204.
    Berman DB, Costalas J, Schultz DC, et al. A common mutation in BRCA2 that predisposes to a variety of cancers is found in both Jewish Ashkenazi and non-Jewish individuals. Cancer Res 1996; 56: 3409–14.PubMedGoogle Scholar
  205. 205.
    Neuhausen SL, Mazoyer S, Friedman L, et al. Haplotype and phenotype analysis of six recurrent BRCA I mutations in 61 families: results of an international study. Am J Hum Genet 1996; 58: 271–80.PubMedGoogle Scholar
  206. 206.
    Csokay B, Tihomirova L, Stengrevics A, et al. Strong founder effects in BRCAI mutation carrier breast cancer patients from Latvia. Mutation in brief no. 258. Hum Mutat 1999; 14: 92.PubMedCrossRefGoogle Scholar
  207. 207.
    Gorski B, Byrski T, Huzarski T, et al. Founder Mutations in the BRCAI Gene in Polish Families with Breast-Ovarian Cancer. Am J Hum Genet 2000; 66: 1963–8.PubMedCrossRefGoogle Scholar
  208. 208.
    Nystrom-Lahti M, Kristo P, Nicolaides NC, et al. Founding mutations and Alu-mediated recombination in hereditary colon cancer. Nat Med 1995; 1: 1203–6.PubMedCrossRefGoogle Scholar
  209. 209.
    Huffer P, Couturier A, Membrez V, et al. Excess of hMLHI germline mutations in Swiss families with hereditary non-polyposis colorectal cancer. Int J Cancer 1998; 78: 680–4.CrossRefGoogle Scholar
  210. 210.
    Narod SA, Goldgar D, Cannon-Albright L, et al. Risk modifiers in carriers of BRCAI mutations. Int J Cancer 1995; 64: 394–8.PubMedCrossRefGoogle Scholar
  211. 211.
    Narod SA, Risch H, Moslehi R, et al. Oral contraceptives and the risk of hereditary ovarian cancer. Hereditary Ovarian Cancer Clinical Study Group. N Engl J Med 1998; 339: 424–8.PubMedCrossRefGoogle Scholar
  212. 212.
    Brunet JS, Ghadirian P, Rebbeck TR, et al. Effect of smoking on breast cancer in carriers of mutant BRCAI or BRCA2 genes. J Natl Cancer Inst 1998; 90: 761–6.PubMedCrossRefGoogle Scholar
  213. 213.
    Weitzel JN, Ding S, Larson GP, et al. The HRAS1 minisatellite locus and risk of ovarian cancer. Cancer Res 2000; 60: 259–61.PubMedGoogle Scholar
  214. 214.
    Laken SJ, Petersen GM, Gruber SB, et al. Familial colorectal cancer in Ashkenazim due to a hypermutable tract in APC. Nat Genet 1997; 17: 79–83.PubMedCrossRefGoogle Scholar
  215. 215.
    Gryfe R, Di Nicola N, Lal G, et al. Inherited colorectal polyposis and cancer risk of the APC 11307K polymorphism. Am J Hum Genet 1999; 64: 378–84.PubMedCrossRefGoogle Scholar
  216. 216.
    Rozen P, Shomrat R, Strul H, et al. Prevalence of the I1307K APC gene variant in Israeli Jews of differing ethnic origin and risk for colorectal cancer. Gastroenterology 1999; 116: 54–7.PubMedCrossRefGoogle Scholar
  217. 217.
    Abrahamson J, Moslehi R, Vesprini D, et al. No association of the 11307K APC allele with ovarian cancer risk in Ashkenazi Jews. Cancer Res 1998; 58: 2919–22.PubMedGoogle Scholar
  218. 218.
    Woodage T, King SM, Wacholder S, et al. The APCI1307K allele and cancer risk in a community-based study of Ashkenazi Jews. Nat Genet 1998; 20: 62–5.PubMedCrossRefGoogle Scholar
  219. 219.
    Redston M, Nathanson KL, Yuan ZQ, et al. The APC I1307K allele and breast cancer risk. Nat Genet 1998; 20: 13–4.PubMedCrossRefGoogle Scholar
  220. 220.
    Yuan ZQ, Begin LR, Wong N, et al. The effect of the I1307K APC polymorphism on the clinicopathological features and natural history of breast cancer. Br J Cancer 1999; 81: 850–4.PubMedCrossRefGoogle Scholar
  221. 221.
    Maresco DL, Arnold PH, Sonoda Y, et al. The APC I1307K allele and BRCAassociated ovarian cancer risk. Am J Hum Genet 1999; 64: 1228–30.PubMedCrossRefGoogle Scholar
  222. 222.
    Buller RE, Sood AK, Lallas T, et al. Association between nonrandom X-chromosome inactivation and BRCA1 mutation in germline DNA of patients with ovarian cancer. J Natl Cancer Inst 1999; 91: 339–46.PubMedCrossRefGoogle Scholar
  223. 223.
    Heinimann K, Scott RJ, Chappuis P, et al. N-acetyltransferase 2 influences cancer prevalence in hMLH1/hMSH2 mutation carriers. Cancer Res 1999; 59: 3038–40.PubMedGoogle Scholar
  224. 224.
    Narod SA. Should a family history be taken from every woman with ovarian cancer. Arch Intern Med 1995; 155: 893–4.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Pierre O. Chappuis
    • 1
  • William D. Foulkes
    • 1
  1. 1.Division of Medical Genetics, Department of MedicineMcGill University Health CenterMontrealCanada

Personalised recommendations