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Familial Cancer

, Volume 4, Issue 2, pp 77–84 | Cite as

High prevalence of two BRCA1 mutations, 4154delA and 5382insC, in Latvia

  • Laima Tikhomirova
  • Olga Sinicka
  • Dagnija Smite
  • Janis Eglitis
  • Shirley V. Hodgson
  • Aivars Stengrevics
Article

Abstract

Our aim was to characterise the germline BRCA1 mutation profile in Latvian breast cancer and ovarian cancer patients, to develop an effective BRCA1 gene mutation detection strategy, and to document genotype–phenotype correlations in mutation carriers. The entire BRCA1 gene was analysed in 75 breast cancer and 30 ovarian cancer patients. Screening for three mutations (5382insC, 4154delA and 300T>G) was carried out in 55 breast cancer and 66 ovarian cancer patients, and for two mutations, 5382insC and 4154delA, in 376 unselected patients with any cancer (including 51 breast cancer and 29 ovarian cancers) and 215 women with any gynaecological tumour. Mutation detection techniques used were SSCP/HD analysis or F-SSCP (ABI PRISM 310). Five different deleterious mutations were detected by analysis of the entire BRCA1 gene. The proportion of cases with mutations amongst 50 breast cancer patients diagnosed before 48 years was 26.0% (95% CI: 14.6–40.3%). Two mutations (5382insC and 4154delA) made up more than 80% of all mutations identified by the analysis of the entire BRCA1 gene in Latvia, at present. Further screening for only the prevalent mutations in different cancer patient groups resulted in the identification of 53 more mutation carriers. We conclude that breast cancer diagnosed before the age of 48 years and ovarian cancer before 65 years are criteria for DNA testing to be offered to women in Latvia, regardless of cancer history in the family. The observed associations of specific prevalent mutations with cancer site and age at onset of disease are discussed.

Keywords

BRCA1 mutations breast and ovarian cancer DNA testing disease manifestation Latvia 

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References

  1. 1.
    Narod, SA, Boyd, J. 2002Current understanding of the epidemiology and clinical implications of BRCA1 and BRCA2 mutations for ovarian cancerCurr Opin Obstet Gynecol141926CrossRefPubMedGoogle Scholar
  2. 2.
    Robson, ME. 2002Clinical considerations in the management of individuals at risk for hereditary breast and ovarian cancerCancer Control9457465PubMedGoogle Scholar
  3. 3.
    Liede, A, Narod, SA. 2002Hereditary breast and ovarian cancer in Asia: genetic epidemiology of BRCA1 and BRCA2Hum Mutat20413424PubMedGoogle Scholar
  4. 4.
    Hopper, JL. 2001Genetic epidemiology of female breast cancerSemin Cancer Biol11367374CrossRefPubMedGoogle Scholar
  5. 5.
    Csokay, B, Tihomirova, L, Stengrevics, A,  et al. 1999Strong founder effects in BRCA1 mutation carrier breast cancer patients from Latvia: mutation in brief no. 258. OnlineHum Mutat1492CrossRefGoogle Scholar
  6. 6.
    Gorski, B, Byrski, T, Huzarski, T,  et al. 2000Founder mutations in the BRCA1 gene in Polish families with breast-ovarian cancerAm J Hum Genet6619631968CrossRefPubMedGoogle Scholar
  7. 7.
    Oszurek, O, Gorski, B, Gronwald, J,  et al. 2001Founder mutations in the BRCA1 gene in west Belarusian breast-ovarian cancer familiesClin Genet60470471CrossRefPubMedGoogle Scholar
  8. 8.
    Tobias, DH, Eng, C, McCurdy, LD,  et al. 2000Founder BRCA 1 and 2 mutations among a consecutive series of Ashkenazi Jewish ovarian cancer patientsGynecol Oncol78148151CrossRefPubMedGoogle Scholar
  9. 9.
    Menkiszak, J, Gronwald, J, Gorski, B,  et al. 2003Hereditary ovarian cancer in PolandInt J Cancer106942945Google Scholar
  10. 10.
    Hodgson, SV, Heap, E, Cameron, J,  et al. 1999Risk factors for detecting germline BRCA1 and BRCA2 founder mutations in Ashkenazi Jewish women with breast or ovarian cancerJ Med Genet36369373PubMedGoogle Scholar
  11. 11.
    Sanjose, S, Leone, M, Berez, V,  et al. 2003Prevalence of BRCA1 and BRCA2 germline mutations in young breast cancer patients: a population-based studyInt J Cancer106588593Google Scholar
  12. 12.
    Struewing, JP, Hartge, P, Wacholder, S,  et al. 1997The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi JewsN Engl J Med33614011408CrossRefPubMedGoogle Scholar
  13. 13.
    Gayther, SA, Harrington, P, Russell, P,  et al. 1997Frequently occurring germ-line mutations of the BRCA1 gene in ovarian cancer families from RussiaAm J Hum Genet6012391242PubMedGoogle Scholar
  14. 14.
    Tereschenko, IV, Basham, VM, Ponder, BA,  et al. 2002BRCA1 and BRCA2 mutations in Russian familial breast cancerHum Mutat19184CrossRefGoogle Scholar
  15. 15.
    Ramus, SJ, Kote-Jarai, Z, Friedman, LS,  et al. 1997Analysis of BRCA1 and BRCA2 mutations in Hungarian families with breast or breast-ovarian cancerAm J Hum Genet6012421246PubMedGoogle Scholar
  16. 16.
    Machackova, E, Foretova, L, Navratilova, M,  et al. 2000A high occurrence of BRCA1 and BRCA2 mutations among Czech hereditary breast and breast–ovarian cancer familiesCas Lek Cesk139635637PubMedGoogle Scholar
  17. 17.
    Grzybowska, E, Zientek, H, Jasinska, A,  et al. 2000High frequency of recurrent mutations in BRCA1 and BRCA2 genes in Polish families with breast and ovarian cancerHum Mutat16482490CrossRefPubMedGoogle Scholar
  18. 18.
    Oszurek, O, Gorski, B, Gronwald, J,  et al. 2001Founder mutations in the BRCA1 gene in west Belarusian breast–ovarian cancer familiesClin Genet60470471CrossRefPubMedGoogle Scholar
  19. 19.
    Friedman, LS, Ostermeyer, EA, Szabo, CI,  et al. 1994Confirmation of BRCA1 by analysis of germline mutations linked to breast and ovarian cancer in ten familiesNat Genet8399404CrossRefPubMedGoogle Scholar
  20. 20.
    Breast Cancer Information Core: http://www.nhgri.nih.gov/ Intramural_research/Lab_transfer/Bic/.Google Scholar
  21. 21.
    Uitenbroek DG. 1997. Binomial. SISA. http://home.clara.net/sisa/binomial.htm. Accessed 1 January 2002.Google Scholar
  22. 22.
    Meindl, A. 2002German consortium for hereditary breast and ovarian cancer: Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German populationInt J Cancer97472480Google Scholar
  23. 23.
    Loginova, AN, Pospekhova, NI, Lyubchenko, LN,  et al. 2003Spectrum of mutations in BRCA1 gene in hereditary forms of breast and ovarian cancer in Russian familiesBull Exp Biol Med136276278CrossRefPubMedGoogle Scholar
  24. 24.
    Backe, J, Hofferbert, S, Skawran, B,  et al. 1999Frequency of BRCA1 mutation 5382insC in German breast cancer patientsGyn Oncol72402406CrossRefGoogle Scholar
  25. 25.
    Gayther, SA, Warren, W, Mazoyer, S,  et al. 1995Germline mutations of the BRCA1 gene in breast and ovarian cancer families provide evidence for a genotype phenotype correlationNat Genet11428433CrossRefPubMedGoogle Scholar
  26. 26.
    Risch, HA, McLaughlin, JR, Cole, DE,  et al. 2001Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancerAm J Hum Genet68700710CrossRefPubMedGoogle Scholar
  27. 27.
    Thompson, D, Easton, D. 2002Breast cancer linkage consortium: variation in BRCA1 cancer risks by mutation positionCancer Epidemiol Biomarkers Prev11329336PubMedGoogle Scholar
  28. 28.
    Hohenstein, P, Fodde, R. 2003Of mice and (wo)men: genotype–phenotype correlations in BRCA1Hum Mol Genet12R271277CrossRefPubMedGoogle Scholar
  29. 29.
    Jasinska, A, Krzyzosiak, WJ. 2001Prevalence of BRCA1 founder mutations in western PolandHum Mutat1775CrossRefGoogle Scholar
  30. 30.
    VanDer Looij, M, Szabo, C, Besznyak, I,  et al. 2000Prevalence of founder BRCA1 and BRCA2 mutations among breast and ovarian cancer patients in HungaryInt J Cancer86737740CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • Laima Tikhomirova
    • 1
  • Olga Sinicka
    • 1
  • Dagnija Smite
    • 1
  • Janis Eglitis
    • 2
  • Shirley V. Hodgson
    • 3
  • Aivars Stengrevics
    • 2
  1. 1.Biomedical Research and Study CentreUniversity of LatviaRigaLatvia
  2. 2.Latvian Oncology CenterLatvian Cancer RegistryRigaLatvia
  3. 3.Thames Regional Genetics CentreLondonUK

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