Abstract
Germline mutations of BRCA1 and BRCA2 predispose to hereditary breast-ovarian cancer syndrome. In Finland, 20 different BRCA1/2 mutations have been identified, and 13 of them are founder mutations that account for the vast majority of Finnish BRCA1/2 families. The purpose of our study was to determine the prevalence of BRCA1/2 mutations in unselected Finnish ovarian carcinoma patients and to evaluate the relationship between mutation carrier status and personal/family history of cancer. Two hundred and thirty-three patients were screened for all the 20 BRCA1/2 mutations known in the Finnish population. Additionally, a subgroup of patients with personal history of breast cancer and/or family history of breast and/or ovarian cancer was screened for novel BRCA1/2 mutations. Thirteen patients (5.6%) had mutations: eleven in BRCA1 and two in BRCA2. All the mutation-positive patients were carriers of the previously known Finnish BRCA1/2 mutations, and seven recurrent founder mutations accounted for 12 of the 13 mutations detected. A logistic regression analysis was used to determine the odds of mutation for ovarian carcinoma patients. The most significant predictor of a mutation was the presence of both breast and ovarian cancer in the same woman, but family history of breast cancer was also strongly related to mutation carrier status. Although BRCA1/2 mutation testing is not warranted in the general Finnish ovarian cancer patient population, patients who have also been diagnosed with breast cancer or have family history of breast or breast and ovarian cancer could benefit from referral to genetic counselling and mutation testing.
Similar content being viewed by others
Article PDF
References
Easton DF, Ford D, Bishop DT, the Breast Cancer Linkage Consortium . Breast and ovarian cancer incidence in BRCA1-mutation carriers Am J Hum Genet 1995 56: 265–271
Ford D, Easton DF, Stratton M et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families Am J Hum Genet 1998 62: 676–689
Easton D . Breast cancer genes–what are the real risks? Nat Genet 1997 16: 210–211
Moslehi R, Chu W, Karlan B et al. BRCA1 and BRCA2 mutation analysis of 208 Ashkenazi Jewish women with ovarian cancer Am J Hum Genet 2000 66: 1259–1272
Risch HA, McLaughlin JR, Cole DE et al. Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer Am J Hum Genet 2001 68: 700–710
Gayther SA, Warren W, Mazoyer S et al. Germline mutations of the BRCA1 gene in breast and ovarian cancer families provide evidence for a genotype-phenotype correlation Nat Genet 1995 11: 428–433
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: 103–105
Breast Cancer Information Core database (BIC): http://www.nhgri.nih.gov/Intramural_research/Lab_transfer/Bic/
Anton-Culver H, Cohen PF, Gildea ME, Ziogas A . Characteristics of BRCA1 mutations in a population-based case series of breast and ovarian cancer Eur J Cancer 2000 36: 1200–1208
Berchuck A, Heron KA, Carney ME et al. Frequency of germline and somatic BRCA1 mutations in ovarian cancer Clin Cancer Res 1998 4: 2433–2437
Stratton JF, Gayther SA, Russell P et al. Contribution of BRCA1 mutations to ovarian cancer N Engl J Med 1997 336: 1125–1130
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: 889–897
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: 737–740
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: 670–677
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: 3663–3665
Tonin PM, Mes-Masson AM, Narod SA, Ghadirian P, Provencher D . Founder BRCA1 and BRCA2 mutations in French Canadian ovarian cancer cases unselected for family history Clin Genet 1999 55: 318–324
Takahashi H, Chiu HC, Bandera CA et al. Mutations of the BRCA2 gene in ovarian carcinomas Cancer Res 1996 56: 2738–2741
Huusko P, Pääkkönen K, Launonen V et al. Evidence of founder mutations in Finnish BRCA1 and BRCA2 families Am J Hum Genet 1998 62: 1544–1548
Vehmanen P, Friedman LS, Eerola H et al. Low proportion of BRCA1 and BRCA2 mutations in Finnish breast cancer families: evidence for additional susceptibility genes Hum Mol Genet 1997 6: 2309–2315
Vehmanen P, Friedman LS, Eerola H et al. A low proportion of BRCA2 mutations in Finnish breast cancer families Am J Hum Genet 1997 60: 1050–1058
Sarantaus L, Huusko P, Eerola H et al. Multiple founder effects and geographical clustering of BRCA1 and BRCA2 families in Finland Eur J Hum Genet 2000 8: 757–763
Syrjäkoski K, Vahteristo P, Eerola H et al. Population-based study of BRCA1 and BRCA2 mutations in 1035 unselected Finnish breast cancer patients J Natl Cancer Inst 2000 92: 1529–1531
Vahteristo P, Eerola H, Tamminen A, Blomqvist C, Nevanlinna H . A probability model for predicting BRCA1 and BRCA2 mutations in breast and breast-ovarian cancer families Br J Cancer 2001 84: 704–708
Friedman LS, Szabo CI, Ostermeyer EA et al. Novel inherited mutations and variable expressivity of BRCA1 alleles, including the founder mutation 185delAG in Ashkenazi Jewish families Am J Hum Genet 1995 57: 1284–1297
Hogervorst FB, Cornelis RS, Bout M et al. Rapid detection of BRCA1 mutations by the protein truncation test Nat Genet 1995 10: 208–212
Håkansson S, Johannsson O, Johansson U et al. Moderate frequency of BRCA1 and BRCA2 germ-line mutations in Scandinavian familial breast cancer Am J Hum Genet 1997 60: 1068–1078
Petrij-Bosch A, Peelen T, van Vliet M et al. BRCA1 genomic deletions are major founder mutations in Dutch breast cancer patients Nat Genet 1997 17: 341–345
Rubin SC, Benjamin I, Behbakht K et al. Clinical and pathological features of ovarian cancer in women with germ- line mutations of BRCA1 N Engl J Med 1996 335: 1455–1456
Jóhannsson ÓT, Ranstam J, Borg Å, Olsson H . Survival of BRCA1 breast and ovarian cancer patients: a population-based study from southern Sweden J Clin Oncol 1998 16: 397–404
Pharoah PD, Easton DF, Stockton DL, Gayther S, Ponder BA, the United Kingdom Coordinating Committee for Cancer Research (UKCCCR) Familial Ovarian Cancer Study Group . Survival in familial, BRCA1-associated, and BRCA2-associated epithelial ovarian cancer Cancer Res 1999 59: 868–871
Boyd J, Sonoda Y, Federici MG et al. Clinicopathologic features of BRCA-linked and sporadic ovarian cancer Jama 2000 283: 2260–2265
Statement of the American Society of Clinical Oncology: Genetic testing for cancer susceptibility, Adopted on February 20, 1996 . J Clin Oncol 1996 14: 1730–1740
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: 1409–1415
Frank TS, Manley SA, Olopade OI et al. Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk J Clin Oncol 1998 16: 2417–2425
Ligtenberg MJ, Hogervorst FB, Willems HW et al. Characteristics of small breast and/or ovarian cancer families with germline mutations in BRCA1 and BRCA2 Br J Cancer 1999 79: 1475–1478
Shattuck-Eidens D, Oliphant A, McClure M et al. BRCA1 sequence analysis in women at high risk for susceptibility mutations: risk factor analysis and implications for genetic testing Jama 1997 278: 1242–1250
Tapper J, Butzow R, Wahlström T, Seppälä M, Knuutila S . Evidence for divergence of DNA copy number changes in serous, mucinous and endometrioid ovarian carcinomas Br J Cancer 1997 75: 1782–1787
Gayther SA, Russell P, Harrington P, Antoniou AC, Easton DF, Ponder BA . 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: 1021–1029
Sutcliffe S, Pharoah PD, Easton DF, Ponder BA . Ovarian and breast cancer risks to women in families with two or more cases of ovarian cancer Int J Cancer 2000 87: 110–117
Lynch HT, de la Chapelle A . Genetic susceptibility to non-polyposis colorectal cancer J Med Genet 1999 36: 801–818
Aaltonen LA, Peltomäki P, Leach FS et al. Clues to the pathogenesis of familial colorectal cancer Science 1993 260: 812–816
Boland CR, Thibodeau SN, Hamilton SR et al. A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer Cancer Res 1998 58: 5248–5257
Lassus H, Laitinen MPE, Anttonen M et al. Comparison of serous and mucinous ovarian carcinomas: distinct pattern of allelic loss at distal 8p and expression of transcription factor GATA-4 Lab Invest; 2001 81: 517–526
Venesmaa P . Epithelial ovarian cancer: impact of surgery and chemotherapy on survival during 1977–1990 Obstet Gynecol 1994 84: 8–11
Acknowledgements
The authors wish to thank Dr Hanna Oksanen for her advice in statistical analyses, Dr Lawrence Brody for kindly providing us the cloned DNA containing the complete BRCA1 cDNA, Ms Gynel Arifdshan for her help in sample collection and preparation, and Ms Merja Lindfors for her technical assistance. We also acknowledge the patients participating in this study. The study was supported by grants from the Academy of Finland, the Finnish Cancer Society, the Clinical Research Fund of Helsinki University Central Hospital (EVO), the Helsinki University Science Foundation, the Foundation of Ella and Georg Ehrnrooth, and the Ida Montin Foundation.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sarantaus, L., Vahteristo, P., Bloom, E. et al. BRCA1 and BRCA2 mutations among 233 unselected Finnish ovarian carcinoma patients. Eur J Hum Genet 9, 424–430 (2001). https://doi.org/10.1038/sj.ejhg.5200652
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ejhg.5200652