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Genetics of Breast and Ovarian Cancer (PDQ®)

  • Updated: 07/11/2014

Table 6. Genetic Modifiers of Breast Cancer Risk

Putative Gene  Chromosome SNP Citation OR (95% CI) Comments 
CI = confidence interval; ER+ = estrogen receptor–positive; ER- = estrogen receptor–negative; OR = odds ratio, SNP = single nucleotide polymorphism.
EMBP1 1p11.2rs11249433[186]1.09 (1.02–1.17)BRCA2 carriers
MDM4 1q32.1rs2290854[187]1.14 (1.09–1.20)BRCA1 carriers
CYP1BI-AS1 2p22.2rs184577[188]0.85 (0.79–0.91)BRCA2 carriers
CASP8 2q33D302H variant[189]0.85 (0.76–0.97)BRCA1 carriers
SLC4A/NEKID 3p24.1rs4973768[130]1.10 (1.03–1.18)BRCA2 carriers
MAP3K1 5q11.2rs889312[130]1.10 (1.01–1.19)BRCA2 carriers
FGF10/MRPS30 5p12rs10941679[130]1.09 (1.01–1.19)BRCA2 carriers
TERT 5p15.33rs2736108[190]0.92 (0.88–0.96)BRCA1 carriers
5p15.33rs10069690[190]1.16 (1.11–1.21)BRCA1 carriers
6q22.23rs218341[191]0.89 (0.80–1.00)BRCA1 carriers
6p24rs9348512[188]0.85 (0.80–0.90)BRCA2 carriers
ESR1 6q25.1rs2046210[186]1.17 (1.11–1.23)BRCA1 carriers
6q25.1rs9397435[186]1.28 (1.18–1.40)BRCA1 carriers
6q25.1rs9397435[186]1.14 (1.01–1.28)BRCA2 carriers
LRRC4C 9q31.2rs965686[192]0.95 (0.89–1.01)BRCA2 carriers
ZNF365 10q21.1rs10995190[192]0.90 (0.82–0.98)BRCA2 carriers
10q21.2rs16917302[193]0.84 (0.72–0.97)BRCA1 carriers, mainly ER+
10q21.2rs16917302[194]0.75 (0.60–0.86)BRCA2 carriers
FGFR2 10q26.13rs2981582[130,195]1.30 (1.20–1.40)BRCA2 carriers
10q26.13rs2981582[130,195]1.35 (1.17–1.56)BRCA1 carriers, ER+
10q26.13rs2981582[130,195]0.91 (0.85–0.98)BRCA1 carriers, ER-
LSP1 11p15.5rs3817198[130]1.14 (1.06–1.23)BRCA2 carriers
PTHLH 12p11rs10771399[192]0.87 (0.81–0.94)BRCA1 carriers
RAD51 15q15.1rs1801320[196]3.18 (1.39–7.27)BRCA2 carriers (CC homozygous only)
TOX3/TNRC9 16q12.1rs3803662[130]1.09 (1.03–1.16)BRCA1 carriers
16q12.1rs3803662[130]1.17 (1.07–1.27)BRCA2 carriers
BRCA1-wild type17prs16942[197]0.86 (0.77–0.95)Wild type modifies BRCA1
BABAM1 19p13.11rs8170[198]1.25 (1.18–1.33)BRCA1 carriers, triple negative
19p13.11rs865686[192]0.86 (0.78–0.95)BRCA2 carriers
19p13.11rs67397200[193]1.17 (1.11–1.23)BRCA1 carriers, mainly ER-
GMEB2 20q13.3rs311499[194]0.72 (0.61–0.85)BRCA2 carriers
FGF13 Xq27.1rs619373[188]1.30 (1.16–3.41)BRCA2 carriers

References

  1. 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]

  2. 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]

  3. Couch FJ, Wang X, McGuffog L, et al.: Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk. PLoS Genet 9 (3): e1003212, 2013.  [PUBMED Abstract]

  4. Gaudet MM, Kuchenbaecker KB, Vijai J, et al.: Identification of a BRCA2-specific modifier locus at 6p24 related to breast cancer risk. PLoS Genet 9 (3): e1003173, 2013.  [PUBMED Abstract]

  5. Engel C, Versmold B, Wappenschmidt B, et al.: Association of the variants CASP8 D302H and CASP10 V410I with breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev 19 (11): 2859-68, 2010.  [PUBMED Abstract]

  6. Bojesen SE, Pooley KA, Johnatty SE, et al.: Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nat Genet 45 (4): 371-84, 384e1-2, 2013.  [PUBMED Abstract]

  7. Kirchhoff T, Gaudet MM, Antoniou AC, et al.: Breast cancer risk and 6q22.33: combined results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2. PLoS One 7 (6): e35706, 2012.  [PUBMED Abstract]

  8. 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]

  9. 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]

  10. Gaudet MM, Kirchhoff T, Green T, et al.: Common genetic variants and modification of penetrance of BRCA2-associated breast cancer. PLoS Genet 6 (10): e1001183, 2010.  [PUBMED Abstract]

  11. Mulligan AM, Couch FJ, Barrowdale D, et al.: Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2. Breast Cancer Res 13 (6): R110, 2011.  [PUBMED Abstract]

  12. 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.  [PUBMED Abstract]

  13. Cox DG, Simard J, Sinnett D, et al.: Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers. Hum Mol Genet 20 (23): 4732-47, 2011.  [PUBMED Abstract]

  14. 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]