BRCA1 and BRCA2 germline mutations in Korean ovarian cancer patients
- 318 Downloads
To evaluate the proportion of Korean ovarian cancer patients with a strong family history and the genetic status in such patients.
Methods and patients
Pedigree analysis and genetic counseling were performed on 337 ovarian cancer patients in the National Cancer Center Korea between January 2005 and June 2008. Patients with a strong family history were defined as (1) patients with double primary ovarian and breast cancer and (2) ovarian cancer patients with one or more first-degree relatives with breast or ovarian cancer. Lymphocyte specimens from peripheral blood were processed for BRCA1 and BRCA2 by direct sequencing.
Sixteen percent (54/337) of patients had a strong family history. Of the 54 patients with a strong family history, 40 patients (74%) accepted the genetic test. Thirteen deleterious mutations (11 in BRCA1 and 2 in BRCA2) were identified (33%). Twenty-three of 283 patients (8%) without a strong family history underwent genetic testing and two deleterious mutations in BRCA1 were identified (9%). Eight of 15 mutations (53%) were novel, and c.1041delAGCinsT and c.2081insC in the BRCA1 gene were recurrent in two patients.
The proportion of Korean ovarian cancer patients with a strong family history was significant, and the prevalence of BRCA1 and BRCA2 mutations in such patients was high.
KeywordsBRCA1 BRCA2 Ovarian cancer Germline mutation Genetics
- Ahn SH, Son BH, Yoon KS, Noh DY, Han W, Kim SW, Lee ES, Park HL, Hong YJ, Choi JJ, Moon SY, Kim MJ, Kim KH, Kwak BS, Cho DY (2007) BRCA1 and BRCA2 germline mutations in Korean breast cancer patients at high risk of carrying mutations. Cancer Lett 245:90–95. doi:10.1016/j.canlet.2005.12.031 PubMedCrossRefGoogle Scholar
- Berek JS, Natarajan S (2007) Ch 35. Ovarian and Fallopian Tube Cancer, 14th edn. Lippincott, Philadelphia, pp 1457–1547Google Scholar
- Boyd J, Sonoda Y, Federici MG, Bogomolniy F, Rhei E, Maresco DL, Saigo PE, Almadrones LA, Barakat RR, Brown CL, Chi DS, Curtin JP, Poynor EA, Hoskins WJ (2000) Clinicopathologic features of BRCA-linked and sporadic ovarian cancer. JAMA 283:2260–2265. doi:10.1001/jama.283.17.2260 PubMedCrossRefGoogle Scholar
- Choi DH, Lee MH, Bail AE, Carter D, Haffy BG (2003) Distint patterns of BRCA1 and BRCA2 mutations in Korean women with early-onset breast cancer. Cancer Res Treat 35:3sGoogle Scholar
- de la Hoya M, Osorio A, Godino J, Sulleiro S, Tosar A, Perez-Segura P, Fernandez C, Rodriguez R, Diaz-Rubio E, Benitez J, Devilee P, Caldes T (2002) Association between BRCA1 and BRCA2 mutations and cancer phenotype in Spanish breast/ovarian cancer families: implications for genetic testing. Int J Cancer 97:466–471. doi:10.1002/ijc.1627 PubMedCrossRefGoogle Scholar
- Easton DF, Deffenbaugh AM, Pruss D, Frye C, Wenstrup RJ, Allen-Brady K, Tavtigian SV, Monteiro AN, Iversen ES, Couch FJ, Goldgar DE (2007) A systematic genetic assessment of 1, 433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes. Am J Hum Genet 81:873–883. doi:10.1086/521032 PubMedCrossRefGoogle Scholar
- Katagiri T, Kasumi F, Yoshimoto M, Nomizu T, Asaishi K, Abe R, Tsuchiya A, Sugano M, Takai S, Yoneda M, Fukutomi T, Nanba K, Makita M, Okazaki H, Hirata K, Okazaki M, Furutsuma Y, Morishita Y, Iino Y, Karino T, Ayabe H, Hara S, Kajiwara T, Houga S, Miki Y et al (1998) High proportion of missense mutations of the BRCA1 and BRCA2 genes in Japanese breast cancer families. J Hum Genet 43:42–48. doi:10.1007/s100380050035 PubMedCrossRefGoogle Scholar
- Khoo US, Ngan HY, Cheung AN, Chan KY, Lu J, Chan VW, Lau S, Andrulis IL, Ozcelik H (2000) Mutational analysis of BRCA1 and BRCA2 genes in Chinese ovarian cancer identifies 6 novel germline mutations. Hum Mutat 16:88–89. doi:10.1002/1098-1004(200007)16:1<88::AID-HUMU16>3.0.CO;2-G PubMedCrossRefGoogle Scholar
- Lee JS, John EM, McGuire V, Felberg A, Ostrow KL, DiCioccio RA, Li FP, Miron A, West DW, Whittemore AS (2006) Breast and ovarian cancer in relatives of cancer patients, with and without BRCA mutations. Cancer Epidemiol Biomarkers Prev 15:359–363. doi:10.1158/1055-9965.EPI-05-0687 PubMedCrossRefGoogle Scholar
- Menkiszak J, Gronwald J, Gorski B, Jakubowska A, Huzarski T, Byrski T, Foszczynska-Kloda M, Haus O, Janiszewska H, Perkowska M, Brozek I, Grzybowska E, Zientek H, Gozdz S, Kozak-Klonowska B, Urbanski K, Miturski R, Kowalczyk J, Pluzanska A, Niepsuj S, Koc J, Szwiec M, Drosik K, Mackiewicz A, Lamperska K, Strozyk E, Godlewski D, Stawicka M, Wasko B, Bebenek M, Rozmiarek A, Rzepka-Gorska I, Narod SA, Lubinski J (2003) Hereditary ovarian cancer in Poland. Int J Cancer 106:942–945. doi:10.1002/ijc.11338 PubMedCrossRefGoogle Scholar
- Modan B, Hartge P, Hirsh-Yechezkel G, Chetrit A, Lubin F, Beller U, Ben-Baruch G, Fishman A, Menczer J, Ebbers SM, Tucker MA, Wacholder S, Struewing JP, Friedman E, Piura B (2001) Parity, oral contraceptives, and the risk of ovarian cancer among carriers and noncarriers of a BRCA1 or BRCA2 mutation. N Engl J Med 345:235–240. doi:10.1056/NEJM200107263450401 PubMedCrossRefGoogle Scholar
- Moslehi R, Chu W, Karlan B, Fishman D, Risch H, Fields A, Smotkin D, Ben-David Y, Rosenblatt J, Russo D, Schwartz P, Tung N, Warner E, Rosen B, Friedman J, Brunet JS, Narod SA (2000) BRCA1 and BRCA2 mutation analysis of 208 Ashkenazi Jewish women with ovarian cancer. Am J Hum Genet 66:1259–1272. doi:10.1086/302853 PubMedCrossRefGoogle Scholar
- Narod SA (2005) Clinical genetics of gynecologic cancer, 4th edn. Lippincott, PhiladelphiaGoogle Scholar
- Pal T, Permuth-Wey J, Betts JA, Krischer JP, Fiorica J, Arango H, LaPolla J, Hoffman M, Martino MA, Wakeley K, Wilbanks G, Nicosia S, Cantor A, Sutphen R (2005) BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. Cancer 104:2807–2816. doi:10.1002/cncr.21536 PubMedCrossRefGoogle Scholar
- Rashid MU, Zaidi A, Torres D, Sultan F, Benner A, Naqvi B, Shakoori AR, Seidel-Renkert A, Farooq H, Narod S, Amin A, Hamann U (2006) Prevalence of BRCA1 and BRCA2 mutations in Pakistani breast and ovarian cancer patients. Int J Cancer 119:2832–2839. doi:10.1002/ijc.22269 PubMedCrossRefGoogle Scholar
- Risch HA, McLaughlin JR, Cole DE, Rosen B, Bradley L, Kwan E, Jack E, Vesprini DJ, Kuperstein G, Abrahamson JL, Fan I, Wong B, Narod SA (2001) Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet 68:700–710. doi:10.1086/318787 PubMedCrossRefGoogle Scholar
- Sekine M, Nagata H, Tsuji S, Hirai Y, Fujimoto S, Hatae M, Kobayashi I, Fujii T, Nagata I, Ushijima K, Obata K, Suzuki M, Yoshinaga M, Umesaki N, Satoh S, Enomoto T, Motoyama S, Tanaka K (2001) Mutational analysis of BRCA1 and BRCA2 and clinicopathologic analysis of ovarian cancer in 82 ovarian cancer families: two common founder mutations of BRCA1 in Japanese population. Clin Cancer Res 7:3144–3150PubMedGoogle Scholar
- Van Der Looij M, Szabo C, Besznyak I, Liszka G, Csokay B, Pulay T, Toth J, Devilee P, King MC, Olah E (2000) Prevalence of founder BRCA1 and BRCA2 mutations among breast and ovarian cancer patients in Hungary. Int J Cancer 86:737–740. doi:10.1002/(SICI)1097-0215(20000601)86:5<737::AID-IJC21>3.0.CO;2-1 CrossRefGoogle Scholar