Table 1. Associations with breast or ovarian cancer risk for loci previously reported to be associated with cancer risk for BRCA1 mutation carriers.
| Locus | Previously published association in BRCA1 | Strongest association in current set of 31,812 BRCA1 GWAS SNPs | Association for published SNP in set of all iCOGS SNPs | ||||||||||
| SNP | all1/all2 (freq) | HR (95%CI) | P | SNP | all1/all2 (freq) | r2 | HR (95%CI) | P | Best tag SNP (r2) | all1/all2 (freq) | HR (95%CI) | P | |
| Loci previously associated with breast cancer risk for BRCA1 carriers | |||||||||||||
| 19p13 | rs8170 | G/A (0.17) | 1.26 (1.17–1.35) | 2.3×10−9 | rs8100241 | G/A (0.52) | 0.31 | 0.84 (0.80–0.88) | 4.3×10−13 | rs8170 (1.0) | G/A (0.17) | 1.22 (1.14–1.29) | 4.8×10−10 |
| 6q25.1 | rs2046210 | C/T (0.35) | 1.17 (1.11–1.23) | 4.5×10−9 | rs3734805 | A/C (0.08) | 0.25 | 1.28 (1.18–1.39) | 5×10−9 | rs2046210* (1.0) | G/A (0.35) | 1.15 (1.10–1.21) | 2.8×10−8 |
| 12p11 | rs10771399 | A/G (0.11) | 0.87 (0.81–0.94) | 3.2×10−4 | rs7957915 | A/G (0.14) | 0.85 | 0.85 (0.79–0.91) | 8.1×10−6 | rs10771399* | A/G (0.11) | 0.85 (0.79–0.92) | 2.7×10−5 |
| TOX3 | rs3803662 | C/T (0.29) | 1.09 (1.03–1.16) | 0.0049 | rs4784220 | A/G (0.38) | 0.52 | 1.08 (1.03–1.13) | 0.0021 | rs3803662* | G/A (0.29) | 1.05 (1.00–1.11) | 0.075 |
| 2q35 | rs13387042a | G/A (0.52) | 1.02 (0.96–1.07) | 0.57 | rs13389571 | A/G (0.05) | 0.02 | 0.86 (0.77–0.96) | 0.011 | rs13387042* | A/G (0.48) | 1.01 (0.96–1.06) | 0.74 |
| Known ovarian cancer susceptibility loci | |||||||||||||
| 9p22 | rs3814113 | T/C (0.34) | 0.78 (0.72–0.85) | 4.8×10−9 | rs3814113 | A/G (0.34) | 1.00 | 0.77 (0.71–0.83) | 5.9×10−11 | rs3814113 (1.0) | A/G (0.34) | 0.77 (0.71–0.83) | 5.9×10−11 |
| 2q31 | rs2072590 | T/C (0.31) | 1.06 (0.98–1.14) | 0.16 | rs1026032 | A/G (0.26) | 0.75 | 1.08 (0.99–1.17) | 0.064 | rs2072590* (1.0) | C/A (0.32) | 1.05 (0.97–1.14) | 0.20 |
| 8q24 | rs10088218 | G/A (0.13) | 0.89 (0.81–0.99) | 0.029 | rs9918771 | A/C (0.17) | 0.31 | 0.86 (0.78–0.95) | 0.0021 | rs10088218 (1.0) | G/A (0.13) | 0.86 (0.78–0.96) | 0.0096 |
| 3q25 | rs2665390 | T/C (0.075) | 1.25 (1.10–1.42) | 2.7×10−3 | rs7651446 | C/A (0.043) | 0.71 | 1.46 (1.25–1.71) | 6.6×10−6 | rs344008 (1.0) | G/A (0.075) | 1.21 (1.07–1.38) | 3.8×10−3 |
| 17q21 | rs9303542 | T/C (0.26) | 1.08 (1.00–1.17) | 0.06 | rs11651753 | G/A (0.43) | 0.36 | 1.14 (1.06–1.23) | 4.6×10−4 | rs9303542* (1.0) | A/G (0.26) | 1.12 (1.04–1.22) | 8.0×10−3 |
| 19p13b | rs67397200 | C/G (0.28) | 1.16 (1.05–1.29) | 3.8×10−4 | c19_pos17158477 | G/C (0.038) | 0.01 | 0.64 (0.49–0.83) | 7.0×10−4 | rs67397200 (c19_pos17262404) | G/C (0.28) | 1.12 (1.01–1.23) | 0.027 |
Freq = frequency of allele 2 in unaffected BRCA1 carriers.
HR = Per allele Hazard Ratio associated with allele 2, under a single disease risk model, unless specified.
r2: correlation between the SNP in the present study and the published SNP.
*
SNP not in BRCA1 GWAS SNP allocation on iCOGS chip.
a
: rs13387042 was previously found to be associated only under the 2-df model.
b
: analysis under a competing risks model.