In English | En español
Questions About Cancer? 1-800-4-CANCER

Genetics of Breast and Ovarian Cancer (PDQ®)

  • Updated: 10/02/2014

Table 11. High-probability Breast Cancer Susceptibility Loci Identified Through Genome-Wide Association Studies

Putative Gene(s) Chromosome  SNP Study Citationa Odds Ratio (OR) (95% Confidence Interval [CI])b Comments 
Intergenic /NOTCH21p11.2rs11249433[94]1.08 (1.02–1.15) [115]Stronger in ER+, low-grade [115]; also in BRCA2 [125]
ERBB2 2q34rs13393577[126]1.53 (1.37–1.70) [126]Identified in Korean subjects [126]
Intergenic2q35rs13387042[113]1.21 (1.14–1.29) [115]Stronger in bilateral and lobular [122]; also in BRCA1 and BRCA2 [127]
SLC4A7, NEK103p24rs4973768[121]1.16 (1.10–1.24) [115]Also in BRCA2 [127]
MRPS30 5p12rs10941679[120]1.11c (1.04–1.19) [115]Strongest in PR+, low-grade [128]; also in BRCA2 [127]
TERT-/CLPTM15p15rs10069690[123]1.25 (1.16–1.34) [123]Strongest in triple-negative [123]
MAP3K1 5q11.2rs889312[112]1.22 (1.14–1.30) [115]Stronger in ER+ [115]; also in BRCA2 [127]
RNF146 6q22rs2180341[116]1.24 (1.13–1.36) [129]Stronger in Ashkenazi Jews [129]
ESR1 6q25.1rs2046210[117]1.15c (1.08–1.22) [115]Also in BRCA1 [125]
TAB2 6q25.1rs9485372[130]0.90 (0.87–0.92) [130]Identified in Chinese subjects [130]
Intergenic7q32.3rs2048672[131]1.11 (1.05–1.17) [131]Identified in East Asian subjects [131]
Intergenic/MYC8q24.21rs13281615[112]1.14 (1.07–1.21) [115]Stronger in ER+ [115]
CDKN2A, CDKN2B 9p21rs1011970[115]1.09 (1.04–1.14) [115]Stronger in ER+ [115]; also in BRCA2 [132]
Intergenic9q31.2rs865686[133]0.89(0.85–0.92) [133]Also in BRCA2 [132]
ANKRD16, FBXO18 10p15.1rs2380205[115]0.94 (0.91–0.98) [115]
ZNF365 10q21.2rs10995190[115]0.86 (0.82–0.91) [115]Stronger in ER+ in general population [115]; also in BRCA2 [134]
ZMIZ1 10q22.3rs704010[115]1.07 (1.03–1.11) [115]
FGFR2 10q26.13rs2981582[112]1.43 (1.35–1.53) [115]Strongest for ER+, low-grade [122]; also in BRCA2 [127]
LSP1 11p15.5rs3817198[112]1.12 (1.05–1.19) [115]Also in BRCA2 [127]
Intergenic11q13rs614367[115]1.15 (1.10–1.20) [115]Restricted to ER+ tumors; strongest for ER+/PR+[115]
BARX211q24.3rs7107217[130]1.08 (1.05–1.11) [130]Identified in Chinese subjects [130]
PTHLH 12p11rs10771399[135]0.85 (0.83–0.88) [135]Also in BRCA1 [132]
Intergenic12q24rs1292011[135]0.92 (0.91–0.94) [135]Restricted to ER+ [135]; also in BRCA2 [132]
RAD51B 14q24.1rs999737[94]0.89 (0.83–0.95) [115]Associated with all subtypes, including triple-negative [95]; also in BRCA2 [132]
TOX3 16q12.1rs3803662[112]1.30 (1.22–1.39) [115]Stronger in ER+ [122]; also in BRCA1 and BRCA2 [127]
COX11 17q23.2rs6504950[121]0.92c (0.86–0.99) [115]
BABAM1 19p13.1rs8170[124]1.26 (1.17–1.35) [136]Restricted to triple-negative in general population [124]; also in BRCA1 [136]
NRIP1 21q21rs2823093[135]0.94 (0.92–0.96) [135]Restricted to ER+ [135]

ER- = estrogen receptor–negative; ER+ = estrogen receptor–positive; PR- = progesterone receptor–negative; PR+ = progesterone receptor–positive; SNP = single nucleotide polymorphism; triple-negative = ER-/PR-/HER2/neu-.
aInitial study that demonstrated genome-wide significance for each locus.
bAll associations observed in the general population, unless otherwise indicated; when relevant, if association was also observed in BRCA1 or BRCA2 mutation carriers, it is indicated.
cOR for best tag SNP was used [115] as a surrogate for published SNP.

References

  1. 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.  [PUBMED Abstract]

  2. 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.  [PUBMED Abstract]

  3. Easton DF, Pooley KA, Dunning AM, et al.: Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447 (7148): 1087-93, 2007.  [PUBMED Abstract]

  4. 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.  [PUBMED Abstract]

  5. 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.  [PUBMED Abstract]

  6. 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.  [PUBMED Abstract]

  7. 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.  [PUBMED Abstract]

  8. 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.  [PUBMED Abstract]

  9. 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.  [PUBMED Abstract]

  10. 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.  [PUBMED Abstract]

  11. 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.  [PUBMED Abstract]

  12. 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.  [PUBMED Abstract]

  13. 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.  [PUBMED Abstract]

  14. 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.  [PUBMED Abstract]

  15. 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.  [PUBMED Abstract]

  16. 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.  [PUBMED Abstract]

  17. 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.  [PUBMED Abstract]

  18. 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.  [PUBMED Abstract]

  19. 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.  [PUBMED Abstract]

  20. 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.  [PUBMED Abstract]

  21. 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.  [PUBMED Abstract]

  22. 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.  [PUBMED Abstract]

  23. 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.  [PUBMED Abstract]

  24. 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.  [PUBMED Abstract]