J Breast Cancer.  2013 Dec;16(4):357-365. 10.4048/jbc.2013.16.4.357.

Distribution of BRCA1 and BRCA2 Mutations in Asian Patients with Breast Cancer

• Kim H
• Choi DH

• KMID: 1976372
• DOI: http://doi.org/10.4048/jbc.2013.16.4.357

Abstract

Breast cancer is the most prevalent cancer in Asian females, and the incidence of breast cancer has been increasing in Asia. Because Asian patients develop breast cancer at a younger age than their Caucasian counterparts, the contributions of BRCA1 and BRCA2 (BRCA1/2) mutations in Asians are expected to be different than in Caucasians. The prevalence of BRCA1/2 mutations in the Asian population varies among countries and studies. Most Asian studies have reported more frequent mutations in BRCA2 than in BRCA1, with the exception of studies from India and Pakistan. In addition, the contribution of large genomic rearrangements of BRCA1/2 genes is relatively small in Asian populations in comparison to other ethnic populations. Various statistical models for the prediction of BRCA1/2 mutations have underestimated the risk of having these genetic mutations in Asians, especially in predicting BRCA2 gene mutation. Until recently, BRCA1/2 mutation analyses in Asia were mostly conducted by independent single institutions with different patient selection criteria and using various genotyping methods. However, a couple of Asian groups have initiated nationwide studies collecting BRCA1/2 mutational data. These national collaborative studies will help a comprehensive understanding of the prevalence of BRCA1/2 mutations in the Asian population.

Keyword

Asians; BRCA genes; Breast neoplasms

MeSH Terms

Asia
Asian Continental Ancestry Group*
Breast Neoplasms*
Breast*
Female
Genes, BRCA2
Humans
Incidence
India
Methods
Models, Statistical
Pakistan
Patient Selection
Prevalence

Reference

1. Shin HR, Carlos MC, Varghese C. Cancer control in the Asia Pacific region: current status and concerns. Jpn J Clin Oncol. 2012; 42:867–881.

2. Jung YS, Na KY, Kim KS, Ahn SH, Lee SJ, Park HK, et al. Nation-wide Korean breast cancer data from 2008 using the breast cancer registration program. J Breast Cancer. 2011; 14:229–236.

3. Yang L, Parkin DM, Ferlay J, Li L, Chen Y. Estimates of cancer incidence in China for 2000 and projections for 2005. Cancer Epidemiol Biomarkers Prev. 2005; 14:243–250.

4. Bradbury AR, Olopade OI. Genetic susceptibility to breast cancer. Rev Endocr Metab Disord. 2007; 8:255–267.

5. Ripperger T, Gadzicki D, Meindl A, Schlegelberger B. Breast cancer susceptibility: current knowledge and implications for genetic counselling. Eur J Hum Genet. 2009; 17:722–731.

6. Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol. 2007; 25:1329–1333.

7. Daly MB, Axilbund JE, Buys S, Crawford B, Farrell CD, Friedman S, et al. Genetic/familial high-risk assessment: breast and ovarian. J Natl Compr Canc Netw. 2010; 8:562–594.

8. Gonzalez-Angulo AM, Timms KM, Liu S, Chen H, Litton JK, Potter J, et al. Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer. Clin Cancer Res. 2011; 17:1082–1089.

9. Robson M, Gilewski T, Haas B, Levin D, Borgen P, Rajan P, et al. BRCA-associated breast cancer in young women. J Clin Oncol. 1998; 16:1642–1649.

10. Young SR, Pilarski RT, Donenberg T, Shapiro C, Hammond LS, Miller J, et al. The prevalence of BRCA1 mutations among young women with triple-negative breast cancer. BMC Cancer. 2009; 9:86.

11. Ferla R, Calò V, Cascio S, Rinaldi G, Badalamenti G, Carreca I, et al. Founder mutations in BRCA1 and BRCA2 genes. Ann Oncol. 2007; 18:Suppl 6. vi93–vi98.

12. Liede A, Narod SA. Hereditary breast and ovarian cancer in Asia: genetic epidemiology of BRCA1 and BRCA2. Hum Mutat. 2002; 20:413–424.

13. Fackenthal JD, Olopade OI. Breast cancer risk associated with BRCA1 and BRCA2 in diverse populations. Nat Rev Cancer. 2007; 7:937–948.

14. Janavičius R. Founder BRCA1/2 mutations in the Europe: implications for hereditary breast-ovarian cancer prevention and control. EPMA J. 2010; 1:397–412.

15. Hall MJ, Reid JE, Burbidge LA, Pruss D, Deffenbaugh AM, Frye C, et al. BRCA1 and BRCA2 mutations in women of different ethnicities undergoing testing for hereditary breast-ovarian cancer. Cancer. 2009; 115:2222–2233.

16. Kim H, Cho DY, Choi DH, Choi SY, Shin I, Park W, et al. Characteristics and spectrum of BRCA1 and BRCA2 mutations in 3,922 Korean patients with breast and ovarian cancer. Breast Cancer Res Treat. 2012; 134:1315–1326.

17. Han SA, Kim SW, Kang E, Park SK, Ahn SH, Lee MH, et al. The prevalence of BRCA mutations among familial breast cancer patients in Korea: results of the Korean Hereditary Breast Cancer study. Fam Cancer. 2013; 12:75–81.

18. Son BH, Ahn SH, Kim SW, Kang E, Park SK, Lee MH, et al. Prevalence of BRCA1 and BRCA2 mutations in non-familial breast cancer patients with high risks in Korea: the Korean Hereditary Breast Cancer (KOHBRA) Study. Breast Cancer Res Treat. 2012; 133:1143–1152.

19. Cao W, Wang X, Li JC. Hereditary breast cancer in the Han Chinese population. J Epidemiol. 2013; 23:75–84.

20. Kwong A, Ng EK, Wong CL, Law FB, Au T, Wong HN, et al. Identification of BRCA1/2 founder mutations in Southern Chinese breast cancer patients using gene sequencing and high resolution DNA melting analysis. PLoS One. 2012; 7:e43994.

21. Sugano K, Nakamura S, Ando J, Takayama S, Kamata H, Sekiguchi I, et al. Cross-sectional analysis of germline BRCA1 and BRCA2 mutations in Japanese patients suspected to have hereditary breast/ovarian cancer. Cancer Sci. 2008; 99:1967–1976.

22. Saxena S, Chakraborty A, Kaushal M, Kotwal S, Bhatanager D, Mohil RS, et al. Contribution of germline BRCA1 and BRCA2 sequence alterations to breast cancer in Northern India. BMC Med Genet. 2006; 7:75.

23. Vaidyanathan K, Lakhotia S, Ravishankar HM, Tabassum U, Mukherjee G, Somasundaram K. BRCA1 and BRCA2 germline mutation analysis among Indian women from south India: identification of four novel mutations and high-frequency occurrence of 185delAG mutation. J Biosci. 2009; 34:415–422.

24. Farooq A, Naveed AK, Azeem Z, Ahmad T. Breast and ovarian cancer risk due to prevalence of BRCA1 and BRCA2 variants in Pakistani population: a Pakistani database report. J Oncol. 2011; 2011:632870.

25. Rashid MU, Zaidi A, Torres D, Sultan F, Benner A, Naqvi B, et al. Prevalence of BRCA1 and BRCA2 mutations in Pakistani breast and ovarian cancer patients. Int J Cancer. 2006; 119:2832–2839.

26. Toh GT, Kang P, Lee SS, Lee DS, Lee SY, Selamat S, et al. BRCA1 and BRCA2 germline mutations in Malaysian women with early-onset breast cancer without a family history. PLoS One. 2008; 3:e2024.

27. Lee DS, Yoon SY, Looi LM, Kang P, Kang IN, Sivanandan K, et al. Comparable frequency of BRCA1, BRCA2 and TP53 germline mutations in a multi-ethnic Asian cohort suggests TP53 screening should be offered together with BRCA1/2 screening to early-onset breast cancer patients. Breast Cancer Res. 2012; 14:R66.

28. Purnomosari D, Pals G, Wahyono A, Aryandono T, Manuaba TW, Haryono SJ, et al. BRCA1 and BRCA2 germline mutation analysis in the Indonesian population. Breast Cancer Res Treat. 2007; 106:297–304.

29. Ginsburg OM, Dinh NV, To TV, Quang LH, Linh ND, Duong BT, et al. Family history, BRCA mutations and breast cancer in Vietnamese women. Clin Genet. 2011; 80:89–92.

30. Kurian AW, Fish K, Shema SJ, Clarke CA. Lifetime risks of specific breast cancer subtypes among women in four racial/ethnic groups. Breast Cancer Res. 2010; 12:R99.

31. Kim EK, Kim KS, Park SK, Ahn SH, Lee MH, Kim SW, et al. The Korean Hereditary Breast Cancer (KOHBRA) Study: protocol review. J Breast Cancer. 2007; 10:241–247.

32. Kwong A, Wong CH, Suen DT, Co M, Kurian AW, West DW, et al. Accuracy of BRCA1/2 mutation prediction models for different ethnicities and genders: experience in a southern Chinese cohort. World J Surg. 2012; 36:702–713.

33. Suter NM, Ray RM, Hu YW, Lin MG, Porter P, Gao DL, et al. BRCA1 and BRCA2 mutations in women from Shanghai China. Cancer Epidemiol Biomarkers Prev. 2004; 13:181–189.

34. Fukutomi T, Ushijima T, Inoue R, Akashi-Tanaka S, Nanasawa T, Tsuda H. BRCA1 and BRCA2 germline mutations in Japanese with hereditary breast cancer families. Breast Cancer. 1997; 4:256–258.

35. Ikeda N, Miyoshi Y, Yoneda K, Shiba E, Sekihara Y, Kinoshita M, et al. Frequency of BRCA1 and BRCA2 germline mutations in Japanese breast cancer families. Int J Cancer. 2001; 91:83–88.

36. Kawahara M, Sakayori M, Shiraishi K, Nomizu T, Takeda M, Abe R, et al. Identification and evaluation of 55 genetic variations in the BRCA1 and the BRCA2 genes of patients from 50 Japanese breast cancer families. J Hum Genet. 2004; 49:391–395.

37. Rajkumar T, Soumittra N, Nancy NK, Swaminathan R, Sridevi V, Shanta V. BRCA1, BRCA2 and CHEK2 (1100 del C) germline mutations in hereditary breast and ovarian cancer families in South India. Asian Pac J Cancer Prev. 2003; 4:203–208.

38. Hedau S, Jain N, Husain SA, Mandal AK, Ray G, Shahid M, et al. Novel germline mutations in breast cancer susceptibility genes BRCA1, BRCA2 and p53 gene in breast cancer patients from India. Breast Cancer Res Treat. 2004; 88:177–186.

39. Liede A, Malik IA, Aziz Z, Rios Pd Pde L, Kwan E, Narod SA. Contribution of BRCA1 and BRCA2 mutations to breast and ovarian cancer in Pakistan. Am J Hum Genet. 2002; 71:595–606.

40. Malik FA, Ashraf S, Kayani MA, Jiang WG, Mir A, Ansar M, et al. Contribution of BRCA1 germline mutation in patients with sporadic breast cancer. Int Semin Surg Oncol. 2008; 5:21.

41. Thirthagiri E, Lee SY, Kang P, Lee DS, Toh GT, Selamat S, et al. Evaluation of BRCA1 and BRCA2 mutations and risk-prediction models in a typical Asian country (Malaysia) with a relatively low incidence of breast cancer. Breast Cancer Res. 2008; 10:R59.

42. De Leon Matsuda ML, Liede A, Kwan E, Mapua CA, Cutiongco EM, Tan A, et al. BRCA1 and BRCA2 mutations among breast cancer patients from the Philippines. Int J Cancer. 2002; 98:596–603.

43. Ewald IP, Ribeiro PL, Palmero EI, Cossio SL, Giugliani R, Ashton-Prolla P. Genomic rearrangements in BRCA1 and BRCA2: a literature review. Genet Mol Biol. 2009; 32:437–446.

44. Lim YK, Lau PT, Ali AB, Lee SC, Wong JE, Putti TC, et al. Identification of novel BRCA large genomic rearrangements in Singapore Asian breast and ovarian patients with cancer. Clin Genet. 2007; 71:331–342.

45. Seong MW, Cho S, Noh DY, Han W, Kim SW, Park CM, et al. Comprehensive mutational analysis of BRCA1/BRCA2 for Korean breast cancer patients: evidence of a founder mutation. Clin Genet. 2009; 76:152–160.

46. Sharifah NA, Nurismah MI, Lee HC, Aisyah AN, Clarence-Ko CH, Naqiyah I, et al. Identification of novel large genomic rearrangements at the BRCA1 locus in Malaysian women with breast cancer. Cancer Epidemiol. 2010; 34:442–447.

47. Kang P, Mariapun S, Phuah SY, Lim LS, Liu J, Yoon SY, et al. Large BRCA1 and BRCA2 genomic rearrangements in Malaysian high risk breast-ovarian cancer families. Breast Cancer Res Treat. 2010; 124:579–584.

48. Kwong A, Ng EK, Law FB, Wong HN, Wa A, Wong CL, et al. Novel BRCA1 and BRCA2 genomic rearrangements in Southern Chinese breast/ovarian cancer patients. Breast Cancer Res Treat. 2012; 136:931–933.

49. Gerhardus A, Schleberger H, Schlegelberger B, Gadzicki D. Diagnostic accuracy of methods for the detection of BRCA1 and BRCA2 mutations: a systematic review. Eur J Hum Genet. 2007; 15:619–627.

50. Haffty BG, Choi DH, Goyal S, Silber A, Ranieri K, Matloff E, et al. Breast cancer in young women (YBC): prevalence of BRCA1/2 mutations and risk of secondary malignancies across diverse racial groups. Ann Oncol. 2009; 20:1653–1659.

51. Anglian Breast Cancer Study Group. Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases. Br J Cancer. 2000; 83:1301–1308.

52. Judkins T, Rosenthal E, Arnell C, Burbidge LA, Geary W, Barrus T, et al. Clinical significance of large rearrangements in BRCA1 and BRCA2. Cancer. 2012; 118:5210–5216.

53. Berry DA, Parmigiani G, Sanchez J, Schildkraut J, Winer E. Probability of carrying a mutation of breast-ovarian cancer gene BRCA1 based on family history. J Natl Cancer Inst. 1997; 89:227–238.

54. Couch FJ, DeShano ML, Blackwood MA, Calzone K, Stopfer J, Campeau L, et al. BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer. N Engl J Med. 1997; 336:1409–1415.

55. Frank TS, Deffenbaugh AM, Reid JE, Hulick M, Ward BE, Lingenfelter B, et al. Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals. J Clin Oncol. 2002; 20:1480–1490.

56. Antoniou AC, Pharoah PP, Smith P, Easton DF. The BOADICEA model of genetic susceptibility to breast and ovarian cancer. Br J Cancer. 2004; 91:1580–1590.

57. Evans DG, Eccles DM, Rahman N, Young K, Bulman M, Amir E, et al. A new scoring system for the chances of identifying a BRCA1/2 mutation outperforms existing models including BRCAPRO. J Med Genet. 2004; 41:474–480.

58. Kurian AW, Gong GD, John EM, Miron A, Felberg A, Phipps AI, et al. Performance of prediction models for BRCA mutation carriage in three racial/ethnic groups: findings from the Northern California Breast Cancer Family Registry. Cancer Epidemiol Biomarkers Prev. 2009; 18:1084–1091.

59. Vogel KJ, Atchley DP, Erlichman J, Broglio KR, Ready KJ, Valero V, et al. BRCA1 and BRCA2 genetic testing in Hispanic patients: mutation prevalence and evaluation of the BRCAPRO risk assessment model. J Clin Oncol. 2007; 25:4635–4641.

60. Kurian AW, Gong GD, Chun NM, Mills MA, Staton AD, Kingham KE, et al. Performance of BRCA1/2 mutation prediction models in Asian Americans. J Clin Oncol. 2008; 26:4752–4758.

61. Rao NY, Hu Z, Yu JM, Li WF, Zhang B, Su FX, et al. Evaluating the performance of models for predicting the BRCA germline mutations in Han Chinese familial breast cancer patients. Breast Cancer Res Treat. 2009; 116:563–570.

62. Kang E, Park SK, Yang JJ, Park B, Lee MH, Lee JW, et al. Accuracy of BRCA1/2 mutation prediction models in Korean breast cancer patients. Breast Cancer Res Treat. 2012; 134:1189–1197.

63. Kang HC, Kim IJ, Park JH, Kwon HJ, Won YJ, Heo SC, et al. Germline mutations of BRCA1 and BRCA2 in Korean breast and/or ovarian cancer families. Hum Mutat. 2002; 20:235.

64. Ahn SH, Son BH, Yoon KS, Noh DY, Han W, Kim SW, et al. BRCA1 and BRCA2 germline mutations in Korean breast cancer patients at high risk of carrying mutations. Cancer Lett. 2007; 245:90–95.

65. Choi DH, Lee MH, Bale AE, Carter D, Haffty BG. Incidence of BRCA1 and BRCA2 mutations in young Korean breast cancer patients. J Clin Oncol. 2004; 22:1638–1645.

66. Seo JH, Cho DY, Ahn SH, Yoon KS, Kang CS, Cho HM, et al. BRCA1 and BRCA2 germline mutations in Korean patients with sporadic breast cancer. Hum Mutat. 2004; 24:350.

67. Han SH, Lee KR, Lee DG, Kim BY, Lee KE, Chung WS. Mutation analysis of BRCA1 and BRCA2 from 793 Korean patients with sporadic breast cancer. Clin Genet. 2006; 70:496–501.

68. Oh JH, Noh DY, Choe KJ, Kang SB, Kim LS, Ro MS, et al. Germline mutation of BRCA1 gene in Korean breast and ovarian cancer patients. J Korean Cancer Assoc. 1995; 27:1061–1069.

69. Seong MW, Cho SI, Noh DY, Han W, Kim SW, Park CM, et al. Low contribution of BRCA1/2 genomic rearrangement to high-risk breast cancer in the Korean population. Fam Cancer. 2009; 8:505–508.

70. Li SS, Tseng HM, Yang TP, Liu CH, Teng SJ, Huang HW, et al. Molecular characterization of germline mutations in the BRCA1 and BRCA2 genes from breast cancer families in Taiwan. Hum Genet. 1999; 104:201–204.

71. Sng JH, Chang J, Feroze F, Rahman N, Tan W, Lim S, et al. The prevalence of BRCA1 mutations in Chinese patients with early onset breast cancer and affected relatives. Br J Cancer. 2000; 82:538–542.

72. Zhi X, Szabo C, Chopin S, Suter N, Wang QS, Ostrander EA, et al. BRCA1 and BRCA2 sequence variants in Chinese breast cancer families. Hum Mutat. 2002; 20:474.

73. Li WF, Hu Z, Rao NY, Song CG, Zhang B, Cao MZ, et al. The prevalence of BRCA1 and BRCA2 germline mutations in high-risk breast cancer patients of Chinese Han nationality: two recurrent mutations were identified. Breast Cancer Res Treat. 2008; 110:99–109.

74. Chen W, Pan K, Ouyang T, Li J, Wang T, Fan Z, et al. BRCA1 germline mutations and tumor characteristics in Chinese women with familial or early-onset breast cancer. Breast Cancer Res Treat. 2009; 117:55–60.

75. Zhang J, Pei R, Pang Z, Ouyang T, Li J, Wang T, et al. Prevalence and characterization of BRCA1 and BRCA2 germline mutations in Chinese women with familial breast cancer. Breast Cancer Res Treat. 2012; 132:421–428.

76. Song CG, Hu Z, Wu J, Luo JM, Shen ZZ, Huang W, et al. The prevalence of BRCA1 and BRCA2 mutations in eastern Chinese women with breast cancer. J Cancer Res Clin Oncol. 2006; 132:617–626.

77. Ang P, Lim IH, Lee TC, Luo JT, Ong DC, Tan PH, et al. BRCA1 and BRCA2 mutations in an Asian clinic-based population detected using a comprehensive strategy. Cancer Epidemiol Biomarkers Prev. 2007; 16:2276–2284.

78. Inoue R, Fukutomi T, Ushijima T, Matsumoto Y, Sugimura T, Nagao M. Germline mutation of BRCA1 in Japanese breast cancer families. Cancer Res. 1995; 55:3521–3524.

79. Inoue R, Ushijima T, Fukutomi T, Fukami A, Sugimura H, Inoue S, et al. BRCA2 germline mutations in Japanese breast cancer families. Int J Cancer. 1997; 74:199–204.

80. Emi M, Matsushima M, Katagiri T, Yoshimoto M, Kasumi F, Yokota T, et al. Multiplex mutation screening of the BRCA1 gene in 1000 Japanese breast cancers. Jpn J Cancer Res. 1998; 89:12–16.

81. Katagiri T, Emi M, Ito I, Kobayashi K, Yoshimoto M, Iwase T, et al. Mutations in the BRCA1 gene in Japanese breast cancer patients. Hum Mutat. 1996; 7:334–339.

82. Kijima G, Murakami Y, Ohuchi N, Satomi S, Sekiya T. Nonsense mutation at codon 63 of the BRCA1 gene in Japanese breast cancer patients. Jpn J Cancer Res. 1998; 89:837–841.

83. Kumar BV, Lakhotia S, Ankathil R, Madhavan J, Jayaprakash PG, Nair MK, et al. Germline BRCA1 mutation analysis in Indian breast/ovarian cancer families. Cancer Biol Ther. 2002; 1:18–21.

84. Valarmathi MT, A A, Deo SS, Shukla NK, Das SN. BRCA1 germline mutations in Indian familial breast cancer. Hum Mutat. 2003; 21:98–99.

85. Valarmathi MT, Sawhney M, Deo SS, Shukla NK, Das SN. Novel germline mutations in the BRCA1 and BRCA2 genes in Indian breast and breast-ovarian cancer families. Hum Mutat. 2004; 23:205.

86. Nanda R, Schumm LP, Cummings S, Fackenthal JD, Sveen L, Ademuyiwa F, et al. Genetic testing in an ethnically diverse cohort of high-risk women: a comparative analysis of BRCA1 and BRCA2 mutations in American families of European and African ancestry. JAMA. 2005; 294:1925–1933.

87. Weitzel JN, Lagos V, Blazer KR, Nelson R, Ricker C, Herzog J, et al. Prevalence of BRCA mutations and founder effect in high-risk Hispanic families. Cancer Epidemiol Biomarkers Prev. 2005; 14:1666–1671.

88. Peto J, Collins N, Barfoot R, Seal S, Warren W, Rahman N, et al. Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer. J Natl Cancer Inst. 1999; 91:943–949.

89. Malone KE, Daling JR, Neal C, Suter NM, O'Brien C, Cushing-Haugen K, et al. Frequency of BRCA1/BRCA2 mutations in a population-based sample of young breast carcinoma cases. Cancer. 2000; 88:1393–1402.

90. Hamann U, Liu X, Bungardt N, Ulmer HU, Bastert G, Sinn HP. Similar contributions of BRCA1 and BRCA2 germline mutations to early-onset breast cancer in Germany. Eur J Hum Genet. 2003; 11:464–467.

91. Loman N, Johannsson O, Kristoffersson U, Olsson H, Borg A. Family history of breast and ovarian cancers and BRCA1 and BRCA2 mutations in a population-based series of early-onset breast cancer. J Natl Cancer Inst. 2001; 93:1215–1223.