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Genetics of Breast and Ovarian Cancer (PDQ®): Genetics - Health Professional Information [NCI] - Low- and Moderate-Penetrance Genes Associated With Breast and / or Ovarian Cancer

Table 9. High-probability Ovarian Cancer Susceptibility Loci Identified Through Genome-Wide Association Studies continued...

Although the statistical evidence for an association between genetic variation at these loci and breast and ovarian cancer risk is overwhelming, the biologically relevant variants and the mechanism by which they lead to increased risk are unknown and will require further genetic and functional characterization. Additionally, these loci are associated with very modest risk (typically, OR <1.5), with more risk variants likely to be identified. No interaction between the SNPs and epidemiologic risk factors for breast cancer have been identified.[135,136] At this time, because their individual and collective influences on cancer risk have not been evaluated prospectively, they are not considered clinically relevant. Furthermore, theoretical models have suggested that common moderate-risk SNPs have limited potential to improve models for individualized risk assessment.[137,138,139] These models used receiver operating characteristic (ROC) curve analysis to calculate the area under the curve (AUC) as a measure of discriminatory accuracy. A more recent study used ROC curve analysis to examine the utility of SNPs in a clinical dataset of greater than 5,500 breast cancer cases and nearly 6,000 controls, using a model with traditional risk factors compared to a model using both standard risk factors and ten previously identified SNPs. The addition of genetic information modestly changed the AUC from 58% to 61.8%, a result that was not felt to be clinically significant. Despite this, 32.5% of patients were in a higher quintile of breast cancer risk when genetic information was included, and 20.4% were in a lower quintile of risk. It remains unclear whether such information has clinical utility.[137,140]

More limited data are available regarding ovarian cancer risk. Three GWAS involving staged analysis of over 10,000 cases and 13,000 controls have been carried out for ovarian cancer.[131,132,134] The seven loci that reached genome-wide significance are shown in Table 9. As in other GWAS, the ORs are modest, generally about 1.2 or weaker, but implicate a number of genes with plausible biological ties to ovarian cancer, such as BABAM1, whose protein complexes with and may regulate BRCA1, and TIRAPR, which codes for a poly (ADP-ribose) polymerase (PARP), molecules that may be important in BRCA1/BRCA2-deficient cells.

In addition to genome-wide studies interrogating common genetic variants, sequencing-based studies involving whole-genome or whole-exome sequencing [141] are also identifying genes associated with breast cancer, such as XRCC2, a rare, moderate-penetrance, breast cancer susceptibility gene.[142]

References:

  1. Easton DF: How many more breast cancer predisposition genes are there? Breast Cancer Res 1 (1): 14-7, 1999.
  2. Smith P, McGuffog L, Easton DF, et al.: A genome wide linkage search for breast cancer susceptibility genes. Genes Chromosomes Cancer 45 (7): 646-55, 2006.
  3. Pharoah PD, Antoniou A, Bobrow M, et al.: Polygenic susceptibility to breast cancer and implications for prevention. Nat Genet 31 (1): 33-6, 2002.
  4. Antoniou AC, Pharoah PP, Smith P, et al.: The BOADICEA model of genetic susceptibility to breast and ovarian cancer. Br J Cancer 91 (8): 1580-90, 2004.
  5. Chen YC, Hunter DJ: Molecular epidemiology of cancer. CA Cancer J Clin 55 (1): 45-54; quiz 57, 2005 Jan-Feb.
  6. Breast Cancer Association Consortium: Commonly studied single-nucleotide polymorphisms and breast cancer: results from the Breast Cancer Association Consortium. J Natl Cancer Inst 98 (19): 1382-96, 2006.
  7. Dunning AM, Healey CS, Pharoah PD, et al.: A systematic review of genetic polymorphisms and breast cancer risk. Cancer Epidemiol Biomarkers Prev 8 (10): 843-54, 1999.
  8. Meijers-Heijboer H, van den Ouweland A, Klijn J, et al.: Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet 31 (1): 55-9, 2002.
  9. Kuschel B, Auranen A, Gregory CS, et al.: Common polymorphisms in checkpoint kinase 2 are not associated with breast cancer risk. Cancer Epidemiol Biomarkers Prev 12 (8): 809-12, 2003.
  10. Sodha N, Bullock S, Taylor R, et al.: CHEK2 variants in susceptibility to breast cancer and evidence of retention of the wild type allele in tumours. Br J Cancer 87 (12): 1445-8, 2002.
  11. Ingvarsson S, Sigbjornsdottir BI, Huiping C, et al.: Mutation analysis of the CHK2 gene in breast carcinoma and other cancers. Breast Cancer Res 4 (3): R4, 2002.
  12. Vahteristo P, Bartkova J, Eerola H, et al.: A CHEK2 genetic variant contributing to a substantial fraction of familial breast cancer. Am J Hum Genet 71 (2): 432-8, 2002.
  13. Meijers-Heijboer H, Wijnen J, Vasen H, et al.: The CHEK2 1100delC mutation identifies families with a hereditary breast and colorectal cancer phenotype. Am J Hum Genet 72 (5): 1308-14, 2003.
  14. Schmidt MK, Tollenaar RA, de Kemp SR, et al.: Breast cancer survival and tumor characteristics in premenopausal women carrying the CHEK2*1100delC germline mutation. J Clin Oncol 25 (1): 64-9, 2007.
  15. Weischer M, Bojesen SE, Tybjaerg-Hansen A, et al.: Increased risk of breast cancer associated with CHEK2*1100delC. J Clin Oncol 25 (1): 57-63, 2007.
  16. Iniesta MD, Gorin MA, Chien LC, et al.: Absence of CHEK2*1100delC mutation in families with hereditary breast cancer in North America. Cancer Genet Cytogenet 202 (2): 136-40, 2010.
  17. Offit K, Pierce H, Kirchhoff T, et al.: Frequency of CHEK2*1100delC in New York breast cancer cases and controls. BMC Med Genet 4 (1): 1, 2003.
  18. Oldenburg RA, Kroeze-Jansema K, Kraan J, et al.: The CHEK2*1100delC variant acts as a breast cancer risk modifier in non-BRCA1/BRCA2 multiple-case families. Cancer Res 63 (23): 8153-7, 2003.
  19. Neuhausen S, Dunning A, Steele L, et al.: Role of CHEK2*1100delC in unselected series of non-BRCA1/2 male breast cancers. Int J Cancer 108 (3): 477-8, 2004.
  20. Ohayon T, Gal I, Baruch RG, et al.: CHEK2*1100delC and male breast cancer risk in Israel. Int J Cancer 108 (3): 479-80, 2004.
  21. CHEK2 Breast Cancer Case-Control Consortium.: CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies. Am J Hum Genet 74 (6): 1175-82, 2004.
  22. Johnson N, Fletcher O, Naceur-Lombardelli C, et al.: Interaction between CHEK2*1100delC and other low-penetrance breast-cancer susceptibility genes: a familial study. Lancet 366 (9496): 1554-7, 2005 Oct 29-Nov 4.
  23. Fletcher O, Johnson N, Dos Santos Silva I, et al.: Family history, genetic testing, and clinical risk prediction: pooled analysis of CHEK2 1100delC in 1,828 bilateral breast cancers and 7,030 controls. Cancer Epidemiol Biomarkers Prev 18 (1): 230-4, 2009.
  24. Weischer M, Bojesen SE, Ellervik C, et al.: CHEK2*1100delC genotyping for clinical assessment of breast cancer risk: meta-analyses of 26,000 patient cases and 27,000 controls. J Clin Oncol 26 (4): 542-8, 2008.
  25. Cybulski C, Wokołorczyk D, Jakubowska A, et al.: Risk of breast cancer in women with a CHEK2 mutation with and without a family history of breast cancer. J Clin Oncol 29 (28): 3747-52, 2011.
  26. Adank MA, Jonker MA, Kluijt I, et al.: CHEK2*1100delC homozygosity is associated with a high breast cancer risk in women. J Med Genet 48 (12): 860-3, 2011.
  27. Gronwald J, Cybulski C, Piesiak W, et al.: Cancer risks in first-degree relatives of CHEK2 mutation carriers: effects of mutation type and cancer site in proband. Br J Cancer 100 (9): 1508-12, 2009.
  28. Wasielewski M, den Bakker MA, van den Ouweland A, et al.: CHEK2 1100delC and male breast cancer in the Netherlands. Breast Cancer Res Treat 116 (2): 397-400, 2009.
  29. Osorio A, Rodríguez-López R, Díez O, et al.: The breast cancer low-penetrance allele 1100delC in the CHEK2 gene is not present in Spanish familial breast cancer population. Int J Cancer 108 (1): 54-6, 2004.
  30. Syrjäkoski K, Kuukasjärvi T, Auvinen A, et al.: CHEK2 1100delC is not a risk factor for male breast cancer population. Int J Cancer 108 (3): 475-6, 2004.
  31. Tsou HC, Teng DH, Ping XL, et al.: The role of MMAC1 mutations in early-onset breast cancer: causative in association with Cowden syndrome and excluded in BRCA1-negative cases. Am J Hum Genet 61 (5): 1036-43, 1997.
  32. Olopade OI, Weber BL: Breast cancer genetics: toward molecular characterization of individuals at increased risk for breast cancer: part I. Cancer: Principles and Practice of Oncology Updates 12(10): 1-12, 1998.
  33. Cybulski C, Górski B, Huzarski T, et al.: CHEK2-positive breast cancers in young Polish women. Clin Cancer Res 12 (16): 4832-5, 2006.
  34. Cybulski C, Huzarski T, Byrski T, et al.: Estrogen receptor status in CHEK2-positive breast cancers: implications for chemoprevention. Clin Genet 75 (1): 72-8, 2009.
  35. Offit K, Garber JE: Time to check CHEK2 in families with breast cancer? J Clin Oncol 26 (4): 519-20, 2008.
  36. Savitsky K, Bar-Shira A, Gilad S, et al.: A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 268 (5218): 1749-53, 1995.
  37. Telatar M, Teraoka S, Wang Z, et al.: Ataxia-telangiectasia: identification and detection of founder-effect mutations in the ATM gene in ethnic populations. Am J Hum Genet 62 (1): 86-97, 1998.
  38. Uhrhammer N, Bay JO, Bignon YJ: Seventh International Workshop on Ataxia-Telangiectasia. Cancer Res 58 (15): 3480-5, 1998.
  39. Ahmed M, Rahman N: ATM and breast cancer susceptibility. Oncogene 25 (43): 5906-11, 2006.
  40. Khanna KK, Chenevix-Trench G: ATM and genome maintenance: defining its role in breast cancer susceptibility. J Mammary Gland Biol Neoplasia 9 (3): 247-62, 2004.
  41. Gilad S, Chessa L, Khosravi R, et al.: Genotype-phenotype relationships in ataxia-telangiectasia and variants. Am J Hum Genet 62 (3): 551-61, 1998.
  42. FitzGerald MG, Bean JM, Hegde SR, et al.: Heterozygous ATM mutations do not contribute to early onset of breast cancer. Nat Genet 15 (3): 307-10, 1997.
  43. Chen J, Birkholtz GG, Lindblom P, et al.: The role of ataxia-telangiectasia heterozygotes in familial breast cancer. Cancer Res 58 (7): 1376-9, 1998.
  44. Bay JO, Grancho M, Pernin D, et al.: No evidence for constitutional ATM mutation in breast/gastric cancer families. Int J Oncol 12 (6): 1385-90, 1998.
  45. Laake K, Vu P, Andersen TI, et al.: Screening breast cancer patients for Norwegian ATM mutations. Br J Cancer 83 (12): 1650-3, 2000.
  46. Dörk T, Bendix R, Bremer M, et al.: Spectrum of ATM gene mutations in a hospital-based series of unselected breast cancer patients. Cancer Res 61 (20): 7608-15, 2001.
  47. Teraoka SN, Malone KE, Doody DR, et al.: Increased frequency of ATM mutations in breast carcinoma patients with early onset disease and positive family history. Cancer 92 (3): 479-87, 2001.
  48. Chenevix-Trench G, Spurdle AB, Gatei M, et al.: Dominant negative ATM mutations in breast cancer families. J Natl Cancer Inst 94 (3): 205-15, 2002.
  49. Thorstenson YR, Roxas A, Kroiss R, et al.: Contributions of ATM mutations to familial breast and ovarian cancer. Cancer Res 63 (12): 3325-33, 2003.
  50. Cavaciuti E, Laugé A, Janin N, et al.: Cancer risk according to type and location of ATM mutation in ataxia-telangiectasia families. Genes Chromosomes Cancer 42 (1): 1-9, 2005.
  51. Olsen JH, Hahnemann JM, Børresen-Dale AL, et al.: Breast and other cancers in 1445 blood relatives of 75 Nordic patients with ataxia telangiectasia. Br J Cancer 93 (2): 260-5, 2005.
  52. Renwick A, Thompson D, Seal S, et al.: ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles. Nat Genet 38 (8): 873-5, 2006.
  53. Thompson D, Duedal S, Kirner J, et al.: Cancer risks and mortality in heterozygous ATM mutation carriers. J Natl Cancer Inst 97 (11): 813-22, 2005.
  54. Levitus M, Waisfisz Q, Godthelp BC, et al.: The DNA helicase BRIP1 is defective in Fanconi anemia complementation group J. Nat Genet 37 (9): 934-5, 2005.
  55. Levran O, Attwooll C, Henry RT, et al.: The BRCA1-interacting helicase BRIP1 is deficient in Fanconi anemia. Nat Genet 37 (9): 931-3, 2005.
  56. Litman R, Peng M, Jin Z, et al.: BACH1 is critical for homologous recombination and appears to be the Fanconi anemia gene product FANCJ. Cancer Cell 8 (3): 255-65, 2005.
  57. Seal S, Thompson D, Renwick A, et al.: Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles. Nat Genet 38 (11): 1239-41, 2006.
  58. Reid S, Schindler D, Hanenberg H, et al.: Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer. Nat Genet 39 (2): 162-4, 2007.
  59. Ding YC, Steele L, Kuan CJ, et al.: Mutations in BRCA2 and PALB2 in male breast cancer cases from the United States. Breast Cancer Res Treat 126 (3): 771-8, 2011.
  60. Rahman N, Seal S, Thompson D, et al.: PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat Genet 39 (2): 165-7, 2007.
  61. Erkko H, Dowty JG, Nikkilä J, et al.: Penetrance analysis of the PALB2 c.1592delT founder mutation. Clin Cancer Res 14 (14): 4667-71, 2008.
  62. Heikkinen T, Kärkkäinen H, Aaltonen K, et al.: The breast cancer susceptibility mutation PALB2 1592delT is associated with an aggressive tumor phenotype. Clin Cancer Res 15 (9): 3214-22, 2009.
  63. Ding YC, Steele L, Chu LH, et al.: Germline mutations in PALB2 in African-American breast cancer cases. Breast Cancer Res Treat 126 (1): 227-30, 2011.
  64. Foulkes WD, Ghadirian P, Akbari MR, et al.: Identification of a novel truncating PALB2 mutation and analysis of its contribution to early-onset breast cancer in French-Canadian women. Breast Cancer Res 9 (6): R83, 2007.
  65. Casadei S, Norquist BM, Walsh T, et al.: Contribution of inherited mutations in the BRCA2-interacting protein PALB2 to familial breast cancer. Cancer Res 71 (6): 2222-9, 2011.
  66. Southey MC, Teo ZL, Dowty JG, et al.: A PALB2 mutation associated with high risk of breast cancer. Breast Cancer Res 12 (6): R109, 2010.
  67. Hellebrand H, Sutter C, Honisch E, et al.: Germline mutations in the PALB2 gene are population specific and occur with low frequencies in familial breast cancer. Hum Mutat 32 (6): E2176-88, 2011.
  68. Bogdanova N, Sokolenko AP, Iyevleva AG, et al.: PALB2 mutations in German and Russian patients with bilateral breast cancer. Breast Cancer Res Treat 126 (2): 545-50, 2011.
  69. Wong MW, Nordfors C, Mossman D, et al.: BRIP1, PALB2, and RAD51C mutation analysis reveals their relative importance as genetic susceptibility factors for breast cancer. Breast Cancer Res Treat 127 (3): 853-9, 2011.
  70. Zheng Y, Zhang J, Niu Q, et al.: Novel germline PALB2 truncating mutations in African American breast cancer patients. Cancer 118 (5): 1362-70, 2012.
  71. Tischkowitz M, Capanu M, Sabbaghian N, et al.: Rare germline mutations in PALB2 and breast cancer risk: a population-based study. Hum Mutat 33 (4): 674-80, 2012.
  72. Jones S, Hruban RH, Kamiyama M, et al.: Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science 324 (5924): 217, 2009.
  73. Slater EP, Langer P, Niemczyk E, et al.: PALB2 mutations in European familial pancreatic cancer families. Clin Genet 78 (5): 490-4, 2010.
  74. Hofstatter EW, Domchek SM, Miron A, et al.: PALB2 mutations in familial breast and pancreatic cancer. Fam Cancer 10 (2): 225-31, 2011.
  75. Stadler ZK, Salo-Mullen E, Sabbaghian N, et al.: Germline PALB2 mutation analysis in breast-pancreas cancer families. J Med Genet 48 (8): 523-5, 2011.
  76. Ghiorzo P, Pensotti V, Fornarini G, et al.: Contribution of germline mutations in the BRCA and PALB2 genes to pancreatic cancer in Italy. Fam Cancer 11 (1): 41-7, 2012.
  77. Cox Angela, Dunning Alison, Garcia-Closas Montserrat, et al.: Nature genetics. Nat Genet 39 (5): 352-8, 2007.
  78. Suwaki N, Klare K, Tarsounas M: RAD51 paralogs: roles in DNA damage signalling, recombinational repair and tumorigenesis. Semin Cell Dev Biol 22 (8): 898-905, 2011.
  79. Vaz F, Hanenberg H, Schuster B, et al.: Mutation of the RAD51C gene in a Fanconi anemia-like disorder. Nat Genet 42 (5): 406-9, 2010.
  80. Meindl A, Hellebrand H, Wiek C, et al.: Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene. Nat Genet 42 (5): 410-4, 2010.
  81. Clague J, Wilhoite G, Adamson A, et al.: RAD51C germline mutations in breast and ovarian cancer cases from high-risk families. PLoS One 6 (9): e25632, 2011.
  82. Thompson ER, Boyle SE, Johnson J, et al.: Analysis of RAD51C germline mutations in high-risk breast and ovarian cancer families and ovarian cancer patients. Hum Mutat 33 (1): 95-9, 2012.
  83. Pelttari LM, Heikkinen T, Thompson D, et al.: RAD51C is a susceptibility gene for ovarian cancer. Hum Mol Genet 20 (16): 3278-88, 2011.
  84. Vuorela M, Pylkäs K, Hartikainen JM, et al.: Further evidence for the contribution of the RAD51C gene in hereditary breast and ovarian cancer susceptibility. Breast Cancer Res Treat 130 (3): 1003-10, 2011.
  85. Romero A, Pérez-Segura P, Tosar A, et al.: A HRM-based screening method detects RAD51C germ-line deleterious mutations in Spanish breast and ovarian cancer families. Breast Cancer Res Treat 129 (3): 939-46, 2011.
  86. Zheng Y, Zhang J, Hope K, et al.: Screening RAD51C nucleotide alterations in patients with a family history of breast and ovarian cancer. Breast Cancer Res Treat 124 (3): 857-61, 2010.
  87. Akbari MR, Tonin P, Foulkes WD, et al.: RAD51C germline mutations in breast and ovarian cancer patients. Breast Cancer Res 12 (4): 404, 2010.
  88. Loveday C, Turnbull C, Ramsay E, et al.: Germline mutations in RAD51D confer susceptibility to ovarian cancer. Nat Genet 43 (9): 879-82, 2011.
  89. Thomas G, Jacobs KB, Kraft P, et al.: A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1). Nat Genet 41 (5): 579-84, 2009.
  90. Figueroa JD, Garcia-Closas M, Humphreys M, et al.: Associations of common variants at 1p11.2 and 14q24.1 (RAD51L1) with breast cancer risk and heterogeneity by tumor subtype: findings from the Breast Cancer Association Consortium. Hum Mol Genet 20 (23): 4693-706, 2011.
  91. Osher DJ, De Leeneer K, Michils G, et al.: Mutation analysis of RAD51D in non-BRCA1/2 ovarian and breast cancer families. Br J Cancer 106 (8): 1460-3, 2012.
  92. Antoniou AC, Sinilnikova OM, Simard J, et al.: RAD51 135G-->C modifies breast cancer risk among BRCA2 mutation carriers: results from a combined analysis of 19 studies. Am J Hum Genet 81 (6): 1186-200, 2007.
  93. He XF, Su J, Zhang Y, et al.: Need for clarification of data in the recent meta-analysis about RAD51 135G>C polymorphism and breast cancer risk. Breast Cancer Res Treat 129 (2): 649-51; author reply 652-3, 2011.
  94. Lu W, Wang X, Lin H, et al.: Mutation screening of RAD51C in high-risk breast and ovarian cancer families. Fam Cancer 11 (3): 381-5, 2012.
  95. Wang WW, Spurdle AB, Kolachana P, et al.: A single nucleotide polymorphism in the 5' untranslated region of RAD51 and risk of cancer among BRCA1/2 mutation carriers. Cancer Epidemiol Biomarkers Prev 10 (9): 955-60, 2001.
  96. Wang Z, Dong H, Fu Y, et al.: RAD51 135G>C polymorphism contributes to breast cancer susceptibility: a meta-analysis involving 26,444 subjects. Breast Cancer Res Treat 124 (3): 765-9, 2010.
  97. Zhou GW, Hu J, Peng XD, et al.: RAD51 135G>C polymorphism and breast cancer risk: a meta-analysis. Breast Cancer Res Treat 125 (2): 529-35, 2011.
  98. Yu KD, Yang C, Fan L, et al.: RAD51 135G>C does not modify breast cancer risk in non-BRCA1/2 mutation carriers: evidence from a meta-analysis of 12 studies. Breast Cancer Res Treat 126 (2): 365-71, 2011.
  99. Solyom S, Aressy B, Pylkäs K, et al.: Breast cancer-associated Abraxas mutation disrupts nuclear localization and DNA damage response functions. Sci Transl Med 4 (122): 122ra23, 2012.
  100. Thorisson GA, Smith AV, Krishnan L, et al.: The International HapMap Project Web site. Genome Res 15 (11): 1592-3, 2005.
  101. Clarke L, Zheng-Bradley X, Smith R, et al.: The 1000 Genomes Project: data management and community access. Nat Methods 9 (5): 459-62, 2012.
  102. Evans DM, Cardon LR: Genome-wide association: a promising start to a long race. Trends Genet 22 (7): 350-4, 2006.
  103. Cardon LR: Genetics. Delivering new disease genes. Science 314 (5804): 1403-5, 2006.
  104. Chanock SJ, Manolio T, Boehnke M, et al.: Replicating genotype-phenotype associations. Nature 447 (7145): 655-60, 2007.
  105. Wellcome Trust Case Control Consortium.: Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447 (7145): 661-78, 2007.
  106. Easton DF, Pooley KA, Dunning AM, et al.: Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447 (7148): 1087-93, 2007.
  107. Stacey SN, Manolescu A, Sulem P, et al.: Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer. Nat Genet 39 (7): 865-9, 2007.
  108. Hunter DJ, Kraft P, Jacobs KB, et al.: A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer. Nat Genet 39 (7): 870-4, 2007.
  109. Turnbull C, Ahmed S, Morrison J, et al.: Genome-wide association study identifies five new breast cancer susceptibility loci. Nat Genet 42 (6): 504-7, 2010.
  110. Gold B, Kirchhoff T, Stefanov S, et al.: Genome-wide association study provides evidence for a breast cancer risk locus at 6q22.33. Proc Natl Acad Sci U S A 105 (11): 4340-5, 2008.
  111. Zheng W, Long J, Gao YT, et al.: Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1. Nat Genet 41 (3): 324-8, 2009.
  112. Kibriya MG, Jasmine F, Argos M, et al.: A pilot genome-wide association study of early-onset breast cancer. Breast Cancer Res Treat 114 (3): 463-77, 2009.
  113. Murabito JM, Rosenberg CL, Finger D, et al.: A genome-wide association study of breast and prostate cancer in the NHLBI's Framingham Heart Study. BMC Med Genet 8 (Suppl 1): S6, 2007.
  114. Stacey SN, Manolescu A, Sulem P, et al.: Common variants on chromosome 5p12 confer susceptibility to estrogen receptor-positive breast cancer. Nat Genet 40 (6): 703-6, 2008.
  115. Ahmed S, Thomas G, Ghoussaini M, et al.: Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2. Nat Genet 41 (5): 585-90, 2009.
  116. Reeves GK, Travis RC, Green J, et al.: Incidence of breast cancer and its subtypes in relation to individual and multiple low-penetrance genetic susceptibility loci. JAMA 304 (4): 426-34, 2010.
  117. Haiman CA, Chen GK, Vachon CM, et al.: A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer. Nat Genet 43 (12): 1210-4, 2011.
  118. Stevens KN, Fredericksen Z, Vachon CM, et al.: 19p13.1 is a triple-negative-specific breast cancer susceptibility locus. Cancer Res 72 (7): 1795-803, 2012.
  119. Antoniou AC, Kartsonaki C, Sinilnikova OM, et al.: Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers. Hum Mol Genet 20 (16): 3304-21, 2011.
  120. Kim HC, Lee JY, Sung H, et al.: A genome-wide association study identifies a breast cancer risk variant in ERBB4 at 2q34: results from the Seoul Breast Cancer Study. Breast Cancer Res 14 (2): R56, 2012.
  121. Antoniou AC, Beesley J, McGuffog L, et al.: Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers: implications for risk prediction. Cancer Res 70 (23): 9742-54, 2010.
  122. Milne RL, Goode EL, García-Closas M, et al.: Confirmation of 5p12 as a susceptibility locus for progesterone-receptor-positive, lower grade breast cancer. Cancer Epidemiol Biomarkers Prev 20 (10): 2222-31, 2011.
  123. Kirchhoff T, Chen ZQ, Gold B, et al.: The 6q22.33 locus and breast cancer susceptibility. Cancer Epidemiol Biomarkers Prev 18 (9): 2468-75, 2009.
  124. Long J, Cai Q, Sung H, et al.: Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer. PLoS Genet 8 (2): e1002532, 2012.
  125. Cai Q, Long J, Lu W, et al.: Genome-wide association study identifies breast cancer risk variant at 10q21.2: results from the Asia Breast Cancer Consortium. Hum Mol Genet 20 (24): 4991-9, 2011.
  126. Antoniou AC, Kuchenbaecker KB, Soucy P, et al.: Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. Breast Cancer Res 14 (1): R33, 2012.
  127. Fletcher O, Johnson N, Orr N, et al.: Novel breast cancer susceptibility locus at 9q31.2: results of a genome-wide association study. J Natl Cancer Inst 103 (5): 425-35, 2011.
  128. Couch FJ, Gaudet MM, Antoniou AC, et al.: Common variants at the 19p13.1 and ZNF365 loci are associated with ER subtypes of breast cancer and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev 21 (4): 645-57, 2012.
  129. Ghoussaini M, Fletcher O, Michailidou K, et al.: Genome-wide association analysis identifies three new breast cancer susceptibility loci. Nat Genet 44 (3): 312-8, 2012.
  130. Antoniou AC, Wang X, Fredericksen ZS, et al.: A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population. Nat Genet 42 (10): 885-92, 2010.
  131. Goode EL, Chenevix-Trench G, Song H, et al.: A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24. Nat Genet 42 (10): 874-9, 2010.
  132. Song H, Ramus SJ, Tyrer J, et al.: A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2. Nat Genet 41 (9): 996-1000, 2009.
  133. Ramus SJ, Kartsonaki C, Gayther SA, et al.: Genetic variation at 9p22.2 and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst 103 (2): 105-16, 2011.
  134. Bolton KL, Tyrer J, Song H, et al.: Common variants at 19p13 are associated with susceptibility to ovarian cancer. Nat Genet 42 (10): 880-4, 2010.
  135. Campa D, Kaaks R, Le Marchand L, et al.: Interactions between genetic variants and breast cancer risk factors in the breast and prostate cancer cohort consortium. J Natl Cancer Inst 103 (16): 1252-63, 2011.
  136. Milne RL, Gaudet MM, Spurdle AB, et al.: Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the breast cancer association consortium: a combined case-control study. Breast Cancer Res 12 (6): R110, 2010.
  137. Pharoah PD, Antoniou AC, Easton DF, et al.: Polygenes, risk prediction, and targeted prevention of breast cancer. N Engl J Med 358 (26): 2796-803, 2008.
  138. Gail MH: Discriminatory accuracy from single-nucleotide polymorphisms in models to predict breast cancer risk. J Natl Cancer Inst 100 (14): 1037-41, 2008.
  139. Gail MH: Value of adding single-nucleotide polymorphism genotypes to a breast cancer risk model. J Natl Cancer Inst 101 (13): 959-63, 2009.
  140. Wacholder S, Hartge P, Prentice R, et al.: Performance of common genetic variants in breast-cancer risk models. N Engl J Med 362 (11): 986-93, 2010.
  141. Shendure J: Next-generation human genetics. Genome Biol 12 (9): 408, 2011.
  142. Park DJ, Lesueur F, Nguyen-Dumont T, et al.: Rare mutations in XRCC2 increase the risk of breast cancer. Am J Hum Genet 90 (4): 734-9, 2012.
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WebMD Public Information from the National Cancer Institute

Last Updated: February 25, 2014
This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.
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