Abstract
To investigate the prevalence of BRCA1 and BRCA2 mutations among Chinese patients, we studied 70 Shanghai cases with early onset breast cancer and affected relatives, and mutation screening was performed in the whole-gene sequence of BRCA1 and BRCA2 by polymerase chain reaction-based denaturing high-performance liquid chromatography. Six disease-causing mutations in BRCA1 (8.6%) and two in BRCA2 (2.9%) were detected, including four novel mutations that were all in the BRCA1 gene (3449insA, IVS17-1G>T, IVS21+1G>C and 5587-1del8). Additional sequence variants identified included 30 polymorphisms (18 in BRCA1 and 12 in BRCA2) and a novel mis-sense mutation of unknown significance in BRCA2 (5911G>C). The 9.5 and 2.4% patients with breast cancer diagnosed before the age of 35 were BRCA1- and BRCA2-mutation carriers, and the prevalence of BRCA1 and BRCA2 mutations in the families with two or more affected individuals were 12.1 and 3.0%, respectively. In these families, all the BRCA1 and BRCA2 mutations were detected in the families containing at least one case diagnosed under the age of 40, and in the families whose youngest patients were diagnosed before the age of 35, the prevalence of BRCA1 and BRCA2 were as high as 40 and 20%, respectively. Based on this information, we conclude that genetic testing should be performed among patients with early onset breast cancer (<40 years), especially combined with family history.
Similar content being viewed by others
References
Arnold N, Gross E, Schwarz-Boeger U, Pfisterer J, Jonat W, Kiechle M (1999) A highly sensitive, fast, and economical technique for mutation analysis in hereditary breast and ovarian cancers. Hum Mutat 14:333–339
Breast Cancer Information Core (BIC): http://www.nhgri.nih.gov/Intramural research/Lab transfer/Bic/
Durocher F, Shattuck-Eidens D, McClure M, Labrie F, Skolnick MH, Goldgar DE, Simard J (1996) Comparison of BRCA1 polymorphisms, rare sequence variants and/or missense mutations in unaffected and breast/ovarian cancer populations. Hum Mol Genet 5:835–842
Eng C, Brody LC, Wagner TM, Devilee P, Vijg J, Szabo C, Tavtigian SV, Nathanson KL, Ostrander E, Frank TS, Steering Committee of the Breast Cancer Information Core (BIC) Consortium (2001) Interpreting epidemiological research: blinded comparison of methods used to estimate the prevalence of inherited mutations in BRCA1. J Med Genet 38:824–833
FitzGerald MG, MacDonald DJ, Krainer M, Hoover I, O’Neil E, Unsal H, Silva-Arrieto S, Finkelstein DM, Beer-Romero P, Englert C, Sgroi DC, Smith BL, Younger JW, Garber JE, Duda RB, Mayzel KA, Isselbacher KJ, Friend SH, Haber DA (1996) Germ-line BRCA1 mutations in Jewish and non-Jewish women with early-onset breast cancer. N Engl J Med 334:143–149
Gal I, Gershoni Baruch R, Haber D, Dagan E, Eisenberg-Barzilai S, Zidan J, Friedman E (2004) The 1100delAT BRCA1 and the 8765delAG BRCA2 mutations: occurrence in high-risk non-Ashkenazi Jews and haplotype comparison of Jewish and non-Jewish carriers. Fam Cancer 3:11–14
Gross E, Arnold N, Pfeifer K, Bandick K, Kiechle M (2000) Identification of specific BRCA1 and BRCA2 variants by DHPLC. Hum Mutat 16:345–353
Hu Z, Wu J, Liu CH, Lu JS, Luo JM, Han QX, Shen ZZ, Shao ZM (2003) The analysis of BRCA1 mutations in eastern Chinese patients with early onset breast cancer and affected relatives. Hum Mutat 22:104
Ikeda N, Miyoshi Y, Yoneda K, Shiba E, Sekihara Y, Kinoshita M, Noguchi S (2001) Frequency of BRCA1 and BRCA2 germline mutations in Japanese breast cancer families. Int J Cancer 91:83–88
Karpukhin AV, Pospekhova NI, Lubchenko LN, Loginova AN, Khomich EV, Budilov AV, Sergeev AS, Zakhar’ev VM, Gar’kavtseva RF, Ginter EK (2002) Frequencies of single-nucleotide polymorphisms and mutations in the BRCA1 gene in patients with hereditary breast or ovarian cancer. Dokl Biol Sci 383:144–146
Malone KE, Daling JR, Thompson JD, O’Brien CA, Francisco LV, Ostrander EA (1998) BRCA1 mutations and breast cancer in the general population: analyses in women before age 35 years and in women before age 45 years with first-degree family history. JAMA 279:922–929
Meyer P, Voigtlaender T, Bartram CR, Klaes R (2003) Twenty-three novel BRCA1 and BRCA2 sequence alterations in breast and/or ovarian cancer families in Southern Germany. Hum Mutat 22:259
Reeves MD, Yawitch TM, van der Merwe NC, van den Berg HJ, Dreyer G, van Rensburg EJ (2004) BRCA1 mutations in South African breast and/or ovarian cancer families: evidence of a novel founder mutation in Afrikaner families. Int J Cancer 110:677–682
Seo JH, Cho DY, Ahn SH, Yoon KS, Kang CS, Cho HM, Lee HS, Choe JJ, Choi CW, Kim BS, Shin SW, Kim YH, Kim JS, Son GS, Lee JB, Koo BH (2004) BRCA1 and BRCA2 germline mutations in Korean patients with sporadic breast cancer. Hum Mutat 24:350
Sng JH, Chang J, Feroze F, Rahman N, Tan W, Lim S, Lehnert M, van der Pool S, Wong J (2000) The prevalence of BRCA1 mutations in Chinese patients with early onset breast cancer and affected relatives. Br J Cancer 82:538–542
Sng JH, Ali AB, Lee SC, Zahar D, Wong JE, Blake V, Sharif A, Cross G, Iau PT (2003) BRCA1 c.2845insA is a recurring mutation with a founder effect in Singapore Malay women with early onset breast/ovarian cancer. J Med Genet 10:e117
Suter NM, Ray RM, Hu YW, Lin MG, Porter P, Gao DL, Zaucha RE, Iwasaki LM, Sabacan LP, Langlois MC, Thomas DB, Ostrander EA (2004) BRCA1 and BRCA2 mutations in women from Shanghai China. Cancer Epidemiol Biomarkers Prev 13:181–189
Tang NL, Pang CP, Yeo W, Choy KW, Lam PK, Suen M, Law LK, King WWK, Johnson P, Hjelm M (1999) Prevalence of mutations in the BRCA1 gene among Chinese patients with breast cancer. J Natl Cancer Inst 91:882–885
Wagner TM, Hirtenlehner K, Shen P, Moeslinger R, Muhr D, Fleischmann E, Concin H, Doeller W, Haid A, Lang AH, Mayer P, Petru E, Ropp E, Langbauer G, Kubista E, Scheiner O, Underhill P, Mountain J, Stierer M, Zielinski C, Oefner P (1999) Global sequence diversity of BRCA2: analysis of 71 breast cancer families and 95 control individuals of worldwide populations. Hum Mol Genet 8:413–423
Acknowledgments
This research was supported in part by the following grants: Grant sponsor: National Key Project of China, Grant number: 2002AA711A08-34, 2001BA703BO5; Grant sponsor: Outstanding Young Investigator Award of National Natural Science Foundation of China, Grant number: 30025015; Grant sponsor: National Natural Science Foundation of China, Grant number: 30371580; Grant sponsor: The Grant from Shanghai Science and Technology Committee; Grant number: 03J14019, 04ZR14027.
Author information
Authors and Affiliations
Corresponding author
Additional information
C-G. Song and Z. Hu contributed equally to the work.
Rights and permissions
About this article
Cite this article
Song, CG., Hu, Z., Wu, J. et al. The prevalence of BRCA1 and BRCA2 mutations in eastern Chinese women with breast cancer. J Cancer Res Clin Oncol 132, 617–626 (2006). https://doi.org/10.1007/s00432-006-0105-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-006-0105-9