Role of BRCA1 and BRCA2 genes in risk of breast cancer

Document Type : Review Article

Authors

1 Associate Professor, Department of Hematology and Oncology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

2 Professor, Institute of biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran.

3 Ph.D Student in Animal Breeding (Molecular Genetics), Department of Animal Science, School of Agriculture, Ferdowsi University of Mashhad, Mashhad, Iran.

Abstract

Introduction: Gene mutations of BRCA1 and BRCA2 in germline can cause risk of breast and ovarian cancers. BRCA1 and BRCA2 genes cause 20% of hereditary breast cancer. The majority of BRCA1 and BRCA2 mutations lead to premature protein termination. This study was performed with aim to investigate the role of BRCA1/2 mutations in risk of breast cancer and introduce some mutations associated with these genes.
Methods: In this systematic review, the information related to the role of BRCA1/2 genes in risk of breast cancer was obtained by searching in databases of PubMed, Scopus, Med-Line, Web of Science, Science Iranian Database and other related websites using the keywords of BRCA mutation, BRCA1, BRCA2, breast cancer and Iran during 1990 to 2015. Finally, 88 articles were chosen that were associated with BRCA1 and BRCA2 genes and their role in risk of breast cancer
Results: This review paper shows more than ever importance of identifying the gene mutations of BRCA1 and BRCA2 carriers in different societies, especially in national and the necessity of planning for families with family history of breast cancer and also screening for mutations in these two genes is felt in clinical programs of the country.
Conclusion: BRCA1/2 genes have great importance and impact on the development and progression of breast cancer. Therefore, these genes can be considered as molecular markers in early detection of breast cancer.

Keywords


  1. Coley HM. Mechanisms and strategies to overcome chemotherapy resistance in metastatic breast cancer. Cancer Treat Rev 2008; 34(4):378-90.
  2. Ripperger T, Gadzicki D, Meindi A, Schlegelberger B. Breast cancer susceptibility: current knowledge and implications for genetic counseling. Eur J Hum Genet 2009; 17(6):722-31.
  3. Falagas ME, Zarkadoulia EA, Ioannidou EN, Peppas G, Christodoulou C, Rafailidis PI. The effect of psychosocial factors on breast cancer outcome: a systematic review. Breast Cancer Res 2007; 9(4):R44.
  4. Tabor MP, Brakenhoff RH, Ruijter-Schippers HJ, Kummer JA, Leemans CR, Braakhuis BJ. Genetically altered fields as origin of locally recurrent head and neck cancer: a retrospective study. Clin Cancer Res 2004; 10(11):3607-13.
  5. Mousavi SM, Montazeri A, Mohagheghi MA, Jarrahi AM, Harirchi I, Najafi M, et al. Breast cancer in Iran: an epidemiological review. Breast J 2007; 13(4):383-91.
  6. Lin Y, Kikuchi S, Tamakoshi K, Kondo T, Niwa Y, Yatsuya H, et al. Active smoking, passive smoking and breast cancer risk: findings from the Japan collaborative cohort study for evaluation of cancer Risk. J Epidemiol 2008; 18(2):77-83.
  7. Zabetian Hoseini M, Nassiri MR, Aslaminejad A, Ghafarzadegan K, Mouseghi A, Ghovvati S, et al. Measurment of human progesterone receptor A expression in normal and breast cancer tissue using real-time PCR technigue. Iran J Obstet Gynecol Infertil 2012;15(1):51-9. (Persian).
  8. Rohlfs EM, Puget N, Graham ML, Weber BL, Garber JE, Skrzynia C, et al. An Alu-mediated 7.1 kb deletion of BRCA1 exons 8 and 9 in breast and ovarian cancer families that results in alternative splicing of exon 10. Genes Chromosomes Cancer 2000; 28(3):300-7.
  9. Casilli F, Di Rocco ZC, Gad S, Tournier I, Stoppa-Lyonnet D, Frebourg T, et al. Rapid detection of novel BRCA1 rearrangements in high-risk breast-ovarian cancer families using multiplex PCR of short fluorescent fragments. Hum Mutat 2002; 20(3):218-26.
  10. Schouten JP, McElgunn CJ, Waaijer R, Zwijnenburg D, Diepvens F, Pals G. Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res 2002; 30(12):e57.
  11. Gudmundsdottir KA, Ashworth A. The roles of BRCA1 and BRCA2 and associated proteins in the maintenance of genomic stability. Oncogene 2006; 25(43):5864-74.
  12. Venkitaraman AR. Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell 2002; 108(2):171-82.
  13. Scully R, Livingston DM. In search of the tumour-suppressor functions of BRCA1 and BRCA2. Nature 2000; 408(6811):429-32.
  14. Kurian AW. BRCA1 and BRCA2 mutations across race and ethnicity: distribution and clinical implications. Curr Opin Obstet Gynecol 2010; 22(1):72-8.
  15. Antoniou A, Cunningham A, Peto J, Evans DG, Lalloo F, Narod SA, et al. The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions. Br J Cancer 2008; 98(8):1457-66.
  16. Scully R, Ganesan S, Vlasakova K, Chen J, Socolovsky M, Livingston DM. Genetic analysis of BRCA1 function in a defined tumor cell line. Mol Cell 1999; 4(6):1093-9.
  17. Brose MS, Rebbeck TR, Calzone KA, Calzone KA, Stopfer JE, Nathanson KL, et al. Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program. J Natl Cancer Inst 2002; 94(18):1365-72.
  18. Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 2003; 72(5):1117-30.
  19. Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet 1998; 62(3):676-89.
  20. Kooshyar MM, Nassiri MR, Karimiani EG, Doosti M, Nasiri K, Rodbari Z. Chromosomal analysis and BRCA2*617delT/88delTG and BRIP1(c.2392C>T) mutations of Fanconi anemia in Iranian family, and its correlation to breast cancer susceptibility. J Chem Pharmaceut Res 2015; 7(10):147-53.
  21. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 1994; 266(5182):66-71.
  22. Scully R, Anderson SF, Chao DM, Wei W, Ye L, Young RA, et al. BRCA1 is a component of the RNA polymerase II holoenzyme. Proc Natl Acad Sci U S A 1997; 94(11):5605-10.
  23. Zhong Q, Chen CF, Li S, Chen Y, Wang CC, Xiao J, et al. Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response. Science 1999; 285(5428):747-50.
  24. Folias A, Matkovic M, Bruun D, Reid S, Hejna J, Grompe M, et al. BRCA1 interacts directly with the Fanconi anemia protein FANCA. Hum Mol Genet 2002; 11(21):2591-7.
  25. Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B, et al. Linkage of early-onset familial breast cancer to chromosome 17q21. Science 1990; 250(4988):1684-9.
  26. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, et al. Identification of the breast cancer susceptibility gene BRCA2. Nature 1995; 378(6559):789-92.
  27. Yang H, Jeffrey PD, Miller J, Kinnucan E, Sun Y, Thoma NH, et al. BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA structure. Science 2002; 297(5588):1837-48.
  28. Hogervorst FB, Nederlof PM, Gille JJ, McElgunn CJ, Grippeling M, Pruntel R, et al. Large genomic deletions and duplications in the BRCA1 gene identified by a novel quantitative method. Cancer Res 2003; 63(7):1449-53.
  29. Mazoyer S. Genomic rearrangements in the BRCA1 and BRCA2 genes. Hum Mutat 2005; 25(5):415-22.
  30. Wang F, Fang Q, Ge Z, Yu N, Xu S, Fan X. Common BRCA1 and BRCA2 mutations in breast cancer families: a meta-analysis from systematic review. Mol Biol Rep 2012; 39(3):2109-18.
  31. 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(10):2222-33.
  32. Keshavarzi F, Javadi GR, Zeinali S. BRCA1 and BRCA2 germline mutations in 85 Iranian breast cancer patients. Fam Cancer 2012; 11(1):57-67.
  33. Nelson-Moseke AC, Jeter JM, Cui H, Roe DJ, Chambers SK, Laukaitis CM, et al. An unusual BRCA mutation distribution in a high risk cancer genetics clinic. Fam Cancer 2012; 11(1):83-7.
  34. Ramus SJ, Friedman LS, Gayther SA, Ponder BA, Bobrow L, van der Looji M, et al. A breast/ovarian cancer patient with germline mutations in both BRCA1 and BRCA2. Nat Genet 1997; 15(1):14-5.
  35. Lavie O, Narod S, Lejbkowicz F, Dishon S, Goldberg Y, Gemer O, et al. Double heterozygosity in the BRCA1 and BRCA2 genes in the Jewish population. Ann Oncol 2011; 22(4):964-6.
  36. Nomizu T, Matsuzaki M, Katagata N, Kobayashi Y, Sakuma T, Monma T, et al. A case of familial breast cancer with double heterozygosity for BRCA1 and BRCA2 genes. Breast Cancer 2012; 22(5):557-61.
  37. Easton DF, Ford D. Bishop DT. Breast and ovarian cancer incidence in BRCA1-mutation carriers, Breast Cancer Link-age Consortium. Am J Hum Genet 1995; 56(1):265-71.
  38. Narod SA, Goldgar D, Cannon-Albright L, WeberB, Moslehi R, Ives E, et al. Risk modifiers in carriers of BRCA1 mutations. Int J Cancer 1995; 64(6):394-8.
  39. Heidemann S, Fischer C, Engel C, Fischer B, Harder L, Schlegelberger B, et al. Double heterozygosity for mutation in BRCA1 and BRCA2 in German breast cancer patients: implications on test strategies and clinical management. Breast Cancer Res Treat 2012; 134(3):1229-39.
  40. Nagy R, Sweet K, Eng C. Highly penetrant hereditary cancer syndromes. Oncogene 2004; 23(38):6445-70.
  41. Ferla R, Calo V, Cascio S, Rinaldi G, Badalamenti G, Carreca I, et al. Founder mutations in BRCA1 and BRCA 2 genes. Ann Oncol 2007; 18(6):93-8.
  42. Kooshyar MM, Nassiri M, Mahdavi M, Doosti M, Parizadeh A. Identification of germline BRCA1 mutations among breast cancer families in Iran, an experience from Northeastern Iran. Asian Pac J Cancer Prev 2013; 14(7):4339-45.
  43. Roa BB, Boyd AA, Volcik K, Richards CS. Ashkenazi Jewish population frequencies for common mutations in BRCA1 and BRCA2. Nat Genet 1996; 14(2):185-7.
  44. Fodor FH, Weston A, Bleiweiss IJ, McCurdy LD, Walsh MM, Tartter PI, et al. Frequency and carrier risk associated with common BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer patients. Am J Hum Genet 1998; 63(1):45-51.
  45. 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(6):1480-90.
  46. Thorlacius S, Olafsdottir G, Tryggvadottir L, Neuhausen S, Jonasson JG, Tavtigian SV, et al. A single BRCA2 mutation in male and female breast cancer families from Iceland with varied cancer phenotypes. Nat Genet 1996; 13(1):117-9.
  47. Einbeigi Z, Bergman A, Meis-Kindblom JM, Flodin A, Bjursell C, Martinsson T, et al. Occurrence of both breast and ovarian cancer in a woman is a mark er for the BRCA gene mutations: a population-based study from western Sweden. Fam Cancer 2007; 6(1):35-41.
  48. Sogaard M, Kruger SK, Cox M, Wozniak E, Hogdall E, Hogdall C, et al. BRCA1 and BRCA2 mutation prevalence and clinical characteristics in an ovarian cancer case population from Denmark. Clin Cancer Res 2008; 14(12):3761-7.
  49. Valarmathi M, Agarwal A, Deo SS, Shukla NK, Satya N. BRCA1 germline mutations in Indian familial breast cancer. Hum Mutat 2002; 21(1):98-9.
  50. Pal T, Permuth-Wey J, Holtje T, Sutphen R. BRCA1 and BRCA2 mutations in a study of African American breast cancer patients. Cancer Epidemiol Biomarkers Prev 2004; 13(11):1794-9.
  51. Liede A, Jack E, Hegele RA, Narod SA. A BRCA1 mutation in native North American families. Hum Mutat 2002; 19(4):460.
  52. Clark SL, Rodriguez AM, Snyder RR, Hankins GD, Boehning D. Structure-function of the tumor suppressor BRCA1. Comput Struct Biotechnol J 2012; 1(1):e201204005.
  53. Thompson D, Easton D, Breast Cancer Linkage Consortium. Variation in BRCA1 cancer risks by mutation position. Cancer Epidemiol Biomarkers Prev 2002; 11(4):329-36.
  54. Risch HA, McLaughlin JR, Cole DE, Rosen B, Bradley L, Fan I, et al. Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin–cohort study in Ontario, Canada. J Natl Cancer Inst 2006; 98(23):1694-706.
  55. Roy R, Chun J, Powell SN. BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nat Rev Cancer 2012; 12(1):68-78.
  56. Evans DG, Shenton A, Woodward E, Lalloo F, Howell A, Maher ER. Penetrance estimates for BRCA1 and BRCA2 based on genetic testing in a Clinical Cancer Genetics service setting: risks of breast/ovarian cancer quoted should reflect the cancer burden in the family. BMC Cancer 2008; 8:155.
  57. Schwartz GF, Hughes KS, Lynch HT, Fabian CJ, Fentiman IS, Robson ME, et al. Proceedings of the international consensus conference on breast cancer risk, genetics, & risk management, April 2007. Cancer 2008; 113(10):2627-37.
  58. Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 2007; 25(11):1329-33.
  59. Mohamad HB, Apffelstaedt JP. Counseling for male BRCA mutation carriers: a review. Breast 2008; 17(5):441-50.
  60. Liede A, Karlan BY, Narod SA. Cancer risks for male carriers of germline mutations in BRCA1 or BRCA2: a review of the literature. J Clin Oncol 2004; 22(4):735-42.
  61. Satagopan JM, Boyd J, Kauff ND, Robson M, Scheuer L, Narod S, et al. Ovarian cancer risk in Ashkenazi Jewish carriers of BRCA1 and BRCA2 mutations. Clin Cancer Res 2002; 8(12):3776-81.
  62. Lakhani SR, Van De Vijver MJ, Jacquemier J, Anderson TJ, Osin PP, McGuffog L, et al. The pathology of familial breast cancer: predictive value of immunohistochemical markers estrogen receptor, progesterone receptor, HER-2, and p53 in patients with mutations in BRCA1 and BRCA2. J Clin Oncol 2002; 20(9):2310-8.
  63. Vaziri SA, Krumroy LM, Elson P, Elson P, Budd GT, Darlington G, et al. Breast tumor immunophenotype of BRCA1-mutation carriers is influenced by age at diagnosis. Clin Cancer Res 2001; 7(7):1937-45.
  64. Phillips KA. Immunophenotypic and pathologic differences between BRCA1 and BRCA2 hereditary breast cancers. J Clin Oncol 2000; 18(21 Suppl):107S-12.
  65. Adem C, Reynolds C, Soderberg CL, Slezak JM, McDonnell SK, Sebo TJ, et al. Pathologic characteristics of breast parenchyma in patients with hereditary breast carcinoma, including BRCA1 and BRCA2 mutation carriers. Cancer 2003; 97(1):1-11.
  66. van der Groep P, Bouter A, van der Zanden R, Siccama I, Menko FH, Gille JJ, et al. Distinction between hereditary and sporadic breast cancer on the basis of clinicopathological data. J Clin Pathol 2006; 59(6):611-7.
  67. Foulkes WD, Brunet JS, Stefansson IM, Straume O, Chappuis PO, Begin LR, et al. The prognostic implication of the basal-like (cyclin Ehigh/p27low/p53+/glomeruloid-microvascular-proliferation+) phenotype of BRCA1-related breast cancer. Cancer Res 2004; 64(3):830-5.
  68. Verhoog LC, Brekelmans CT, Seynaeve C, Dahmen G, van Geel AN, Bartels CC, et al. Survival in hereditary breast cancer associated with germline mutations of BRCA2. J Clin Oncol 1999; 17(11):3396-402.
  69. Senst N, Llacuachaqui M, Lubinski J, Lynch H, Armel S, Neuhausen S, et al. Parental origin of mutation and the risk of breast cancer in a prospective study of women with a BRCA1 or BRCA2 mutation. Clin Genet 2012; 84(1):43-6.
  70. Cortesi L, Turchetti D, Bertoni C, Bellei R, Mangone L, Vinceti M, et al. Comparison between genotype and phenotype identifies a high-risk population carrying BRCA1 mutations. Genes Chromosomes Cancer 2000; 27(2):130-5.
  71. Neamatzadeh H, Shiryazdi SM, Kalantar SM. BRCA1 and BRCA2 mutations in Iranian breast cancer patients: a systematic review. J Res Med Sci 2015; 20(3):284-93.
  72. Saleh-Gohari N, Mohammadi-Anaie M, Kalantari-Khandani B. BRCA1 gene mutations in breast cancer patients from Kerman Province, Iran. Iran J Cancer Prev 2012; 5(4):210-5.
  73. Yassaee VR, Zeinali S, Harirchi I, Jarvandi S, Mohagheghi MA, Hornby DP, et al. Novel mutations in the BRCA1 and BRCA2 genes in Iranian women with early‑onset breast cancer. Breast Cancer Res 2002; 4(4):R6.
  74. Mehdipour P, Hosseini-Asl S, Savabi-E A, Habibi L, Alvandi E, Atri M. Low frequency of 185delAG founder mutation of BRCA1 gene in Iranian breast cancer patients. J Cancer Mol 2006; 2(3):123-7.
  75. Fattahi MJ, Mojtahedi Z, Karimaghaee N, Talei AR, Banani SJ, Ghaderi A. Analysis of BRCA1 and BRCA2 mutations in southern Iranian breast cancer patients. Arch Iran Med 2009; 12(6):584‑7.
  76. Ghorbanpoor S, Bidmeshkipoor A, Mirmomeni MH, Khazaee S. Role of BRCA1 gene mutations in sporadic cases of breast cancer in Kermanshah. Sci J Kurdistan Univ Med Sci 2010; 14(4):60-71. (Persian).
  77. Warner E, Hill K, Causer P, Plewes D, Jong R, Yaffe M, et al. A prospective study of breast cancer incidence in women with a BRCA1 or BRCA2 mutation under surveillance with and without magnetic resonance imaging. J Clin Oncol 2011; 29(13):1664-9.
  78. Goss PE, Ingle JN, Alés-Martínez JE, Cheung AM, Chlebowski RT, Wactawski-Wende J, et al. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med 2011; 364(25):2381-91.
  79. Nooshinfar E, Bashash D, Khodakarami N, Mohamadi G, Taghavi A, Shahani M, et al. Melatonin and its importance in Breast cancer prevention and treatment (A purposed review article). Iran J Obstet Gynecol Infertil 2014; 17(118):10-21. (Persian).
  80. Akbari ME, Khayamzadeh M, Khoshnevis SJ, Nafisi N, Akbari A. Five and ten years survival in breast cancer patients mastectomies vs. breast conserving surgeries personal experience. Iran J Cancer Prev 2012; 1(2):53-6.
  81. Gronwald J, Tung N, Foulkes WD, Offit K, Gershoni R, Daly M, et al. Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update. Int J Cancer 2006; 118(9):2281-4.
  82. Hay T, Matthews JR, Pietzka L, Lau A, Cranston A, Nygren AO, et al. Poly(ADP-ribose) polymerase-1 inhibitor treatment regresses autochthonous Brca2/p53-mutant mammary tumors in vivo and delays tumor relapse in combination with carboplatin. Cancer Res 2009; 69(9):3850-5.
  83. Schramek D, Leibbrandt A, Sigl V, Kenner L, Pospisilik JA, Lee HJ, et al. Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancer. Nature 2010; 468(7320):98-102.
  84. Khadivi R, Harrirchi I, Akbari ME. Ten year breast cancer screening and follow up in 52200 women in Shahre-Kord, Iran (1997-2006). Iran J Cancer Prev 2008; 1(2):73-7.
  85. Sadjadi A, Sadjadi M, Mohagheghi MA, Mousavi-Jarrahi A, Malekezadeh R, Parkin DM. Cancer occurrence in Iran in 2002, an international perspective. Asian Pac J Cancer Prev 2005; 6(3):359-63.
  86. Bougie O, Weberpals JI. Clinical considerations of BRCA1‑ and BRCA2‑mutation carriers: a review. Int J Surg Oncol 2011; 2011:374012.
  87. Narod SA, Foulkes WD. BRCA1 and BRCA2: 1994 and beyond. Nat Rev Cancer 2004; 4(9):665-76.
  88. Xu B, Kim ST, Kastan MB. Involvement of Brca1 in S-phase and G(2)-phase checkpoints after ionizing irradiation. Mol Cell Biol 2001; 21(10):3445-50.