Table 2.
Regions of the genome that showed the strongest associations with AJ breast cancer after phase 2 of the study
| SNP* | Chr† | Gene/region‡ | χ2P value of allele frequency (top rank no.)§ |
χ2P value aggregate¶ | OR allele for risk‖ (95% CI) | OR dom.** (95% CI) | OR rec.†† (95% CI) | MAFcs | MAFcn | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Phase 1 | Phase 2 | Phase3 | |||||||||
| rs6569479 | 6q22.33 | ECHDC1; RNF146 | 6.0 × 10−3 (1,358) | 9.8 × 10−5 (1) | 2.2 × 10−2 | 1.2 × 10−7 | 1.39 (1.23–1.57) | 1.50 (1.29–1.74) | 1.48 (1.07–2.04) | 0.271 | 0.211 |
| rs7776136 | 6q22.33 | ECHDC1; RNF146 | 2.7 × 10−3 (742) | 9.9 × 10−5 (2) | 2 × 10−2 | 6.6 × 10−8 | 1.39 (1.23–1.57) | 1.51 (1.31–1.76) | 1.42 (1.05–1.90) | 0.278 | 0.217 |
| rs2180341 | 6q22.33 | ECHDC1; RNF146 | 8.9 × 10−4 (205) | 1.1 × 10−4 (3) | 1.8 × 10−2 | 2.9 × 10−8 | 1.41 (1.25–1.59) | 1.53 (1.32–1.77) | 1.51 (1.10–2.08) | 0.273 | 0.211 |
| rs6569480 | 6q22.33 | ECHDC1; RNF146 | 2.2 × 10−3 (616) | 1.2 × 10−4 (4) | 2 × 10−2 | 6.1 × 10−8 | 1.40 (1.24–1.58) | 1.51 (1.30–1.75) | 1.51 (1.10–2.08) | 0.272 | 0.211 |
| rs1078806 | 10q26.13 | FGFR2 | 4.5 × 10−2 (10,062) | 8.6 × 10−4 (5) | 4 × 10−2 | 1.5 × 10−5 | 1.26 (1.13–1.40) | 1.32 (1.13–1.54) | 1.40 (1.16–1.69) | 0.455 | 0.399 |
| rs3012642 | 23q13.1 | PHKA1; HDAC8 | 2.1 × 10−2 (4,751) | 2.1 × 10−3 (6) | 7.7 × 10−2 | NS | NS | NS | NS | 0.034 | 0.039 |
| rs7203563 | 16p13.3 | A2BP1 | 2.5 × 10−2 (5,573) | 3.3 × 10−3 (7) | 0.57 | 1.8 × 10−3 | 1.32 (1.11–1.57) | 1.36 (1.13–1.64) | NS | 0.110 | 0.086 |
NS, not significant; dom., dominant; rec., recessive; MAFcs, minor allele frequency in cases; MAFcn, minor allele frequency in controls.
*Included are all SNPs that had P < 0.01 based on the analysis of the phase 2 case-control data (see §).
†Chromosome position by cytogenetic band.
‡Genes identified in the genome browser that are within 100 kb on either side of the SNP indicated.
§Phase 1 consisted of 249 AJ probands from multiplex families in whom a mutation in BRCA1 and BRCA2 was excluded versus 299 cancer-free AJ controls; phase 2 consisted of 950 consecutive AJ breast cancer cases versus 979 cancer-free AJ controls; phase 3 consisted of an additional 243 AJ breast cancer cases from MSKCC and an independent 187 AJ cancer-free controls (rank no. represents the top order of the SNP of the total SNPs analyzed in phases 1 and 2).
¶Aggregate data consisted of the combined phases 1, 2, and 3.
‖OR calculated by using the aggregate data and based on the χ 2 test of the alleles inverted to express the risk allele when necessary; 95% CI.
**OR calculated by using the aggregate data and based on the χ 2 test of the dominant model.
††OR calculated by using the aggregate data and based on the χ 2 test of the recessive model.