Mammary Tumor Development in Dogs Is Associated with BRCA1 and BRCA2

Patricio Rivera; Malin Melin; Tara Biagi; Tove Fall; Jens Häggström; Kerstin Lindblad-Toh; Henrik von Euler

doi:10.1158/0008-5472.CAN-09-1725

DOI: 10.1158/0008-5472.CAN-09-1725 Published November 2009

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Table 1.

Genes evaluated for association to CMT risk

Gene	Human chromosome	Canine chromosome	No. SNPs	Span covered
BRCA2	13	25	4	10.729–10.786 Mb
BRCA1	17	9	8	23.278–23.399 Mb
FGFR2	10	28	9	34.303–34.406 Mb
TOX3	16	2	7	65.949–65.964 Mb
CHEK2	22	26	6	25.089–25.133 Mb
MAP3K1	5	2	6	46.823–46.858 Mb
LSP1	11	18	6	49.138–49.143 Mb
RCAS1	8	13	5	13.125–13.138 Mb
TP53	17	5	7	35.617–35.686 Mb
ERBB2	17	9	5	26.098–26.110 Mb

Table 2.

Association of the best single SNP in each gene to CMT risk

Gene	Best P_raw data set 1	Best P_raw data set 2	Best P_raw total	Best P_Bonf total	Odds ratio total	F_cases/F_controls total
BRCA2	0.0032	6.7 × 10⁻⁴	3.9 × 10⁻⁶	1.4 × 10⁻⁴	4.24	0.97:0.88
BRCA1	0.012	0.18	1.3 × 10⁻⁴	0.0049	3.74	0.97:0.91
FGFR2	0.018	0.11	0.0047	0.18	1.88	0.90:0.83
TOX3	0.29	0.023	0.014	0.52	1.80	0.92:0.86
CHEK2	0.37	0.015	0.034	1.0	1.40	0.57:0.49
MAP3K1	0.025	0.54	0.042	1.0	1.43	0.79:0.72
LSP1	0.036	0.64	0.11	1.0	1.45	0.89:0.85
RCAS1	0.25	0.063	0.16	1.0	1.42	0.91:0.88
TP53	0.010	0.80	0.20	1.0	1.23	0.38:0.33
ERBB2	0.30	0.33	0.24	1.0	1.45	0.95:0.93
N_cases	89	122	212	212	212	212
N_controls	85	59	143	143	143	143

Abbreviations: P_raw, the best χ² single SNP P value obtained for each gene [nominal association (P_raw < 0.05) is indicated in bold]; P_Bonf, Bonferroni corrected P values [significant association (P_Bonf < 0.05) is indicated in bold]; F_cases/F_controls, the risk allele frequency in cases and controls.

Table 3.
Association of the best haplotypes in each gene to CMT risk
Gene N_SNPs Best P_raw Best P_Bonf
BRCA2 2 4.8 × 10⁻⁶ 2.6 × 10⁻⁴
BRCA1 5 1.5 × 10⁻⁴ 0.0082
FGFR2 7 0.019 1.0
TOX3 6 0.025 1.0
CHEK2 5 0.070 1.0
MAP3K1 2 0.065 1.0
LSP1 N.A. N.A. N.A.
RCAS1 5 0.19 1.0
TP53 N.A. N.A. N.A.
ERBB2 3 0.20 1.0
NOTE: N_SNPs, number of SNPs included in the haplotypes; P_raw, the best χ² haplotype P value obtained for each gene [nominal association (P_raw < 0.05) is indicated in bold]; P_Bonf, Bonferroni corrected P values [significant association (P_Bonf < 0.05) is indicated in bold]; N_cases, 212; N_controls, 143.

Table 4.

Association of the best single SNP in each gene to malignant and benign tumor risk (data set 1)

Gene	Best P_raw malignant versus controls	Best P_raw benign versus controls	Best P_raw malignant versus benign
BRCA2	0.020	0.032	0.97
BRCA1	0.0068	0.086	0.027
FGFR2	0.027	0.068	0.067
TOX3	0.34	0.051	0.023
CHEK2	0.60	0.37	0.41
MAP3K1	0.044	0.028	0.12
LSP1	0.044	0.17	0.32
RCAS1	0.038	0.25	018
TP53	0.82	0.036	0.14
ERBB2	0.75	0.28	0.44
N_cases	28	53	26
N_controls	84	84	50

Abbreviation: P_raw, the best χ² single SNP P value obtained for each gene. Nominal association (P_raw < 0.05) is indicated in bold. None of the SNPs gives significant P values after Bonferroni correction.