Additional file 1: Table S1. of Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women

Ethics committees that granted approval for the access and use of the data for this study. Table S2. Participant counts by center and mutation. Table S3. Primers used for PCR and Sanger sequencing. Table S4. Primers used in micro-satellite analysis for loss of heterozygosity. Table S5. Micro-satellite loss of heterozygosity and sequencing analysis results. (DOC 177 kb

Additional file 2: of Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2

List of local ethics committees that granted approval for the access and use of the data in present study. (DOCX 23 kb

Per allele hazard ratios (HR) and 95% confidence intervals (CI) of previously published breast cancer loci among <i>BRCA2</i> mutation carriers from previous reports and from the iCOGS array, ordered by statistical significance of the region.

1<p>Reporting status of the SNP is either previously reported or novel to this report.</p>2<p>p-value was calculated based on the 1-degree of freedom score test statistic.</p>3<p>rs311499 could not be designed onto the iCOGS array. A surrogate (r² = 1.0), rs311498, was included, however, and reported here.</p>4<p>Stronger associations were originally reported for the SNP, assuming a dominant or recessive model of the ‘risk allele’.</p

Associations between SNPs in the region surrounding rs9348512 on chromosome 6 and breast cancer risk.

<p>Results based on imputed and observed genotypes. The blue spikes indicate the recombination rate at each position. Genotyped SNPs are represented by diamonds and imputed SNPs are represented by squares. Color saturation indicates the degree of correlation with the SNP rs9348512.</p

Breast cancer hazard ratios (HR) and 95% confidence intervals (CI) of novel breast cancer loci with P-values of association <10⁻⁵ among <i>BRCA2</i> mutation carriers.

1<p>P-value was calculated based on the 1-degree of freedom score test.</p

Pairwise correlations (r²) between selected SNPs.

<p>SNPs correspond to: rs10124837, the strongest associated in <i>BRCA1</i>; rs62543583, the strongest associated in <i>BRCA2</i> mutation carriers; rs7046326, the strongest associated in <i>BRCA1/2</i> meta-analysis; rs3814113, was the strongest associated variant in the initial GWAS analysis.</p

Associations between SNPs in 9p22.2 with ovarian cancer risk for <i>BRCA1</i> and <i>BRCA2</i> mutation carriers.

<p>In each plot, the purple diamond corresponds to the strongest associated SNP and the colour code indicates the linkage disequilibrium with respect to this variant. Horizontal lines indicate the -log₁₀ p-value such that the SNPs above the line are the potential causal ones. This set was defined based on a likelihood ratio for a particular SNP as being less or equal than 100, relative to the most likely variant and r²>0.1. (A) <i>BRCA1</i> mutation carriers, (B) <i>BRCA2</i> mutation carriers.</p

Genomic features surrounding the 9p22.2 locus.

<p>Illustration of the genomic region (chr9:16,839,835–16,924,468) encompassing peaks (shaded areas) containing candidate causal variants associated with ovarian cancer risk in <i>BRCA1</i> and <i>BRCA2</i> mutation carriers. Epigenomic data from Coetzee et al., (2015) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0158801#pone.0158801.ref020" target="_blank">20</a>] representing potential regulatory elements in ovarian cells (iOSE4 and iOSE11) and fallopian tube (FTSEC33) cells derived from formaldehyde assisted identification of regulatory elements sequencing (FAIRE-seq) and histone modification ChIP-seq are shown as black bars. Variants which overlap one of these features are coloured red. Data from the ENCODE project including histone modification ChIP-seq for three modifications (H3K4me1, H3K4me3, and H3K27ac) are shown as coloured histograms, as well as DNaseI hypersensitive site mapping and transcription factor ChIP-seq. The positions of all common SNPs from dbSNP build 142 are shown in the lowest track.</p

Associations between SNPs in 9p22.2 with ovarian cancer risk for the meta-analysis of <i>BRCA1</i> and <i>BRCA2</i> mutation carriers.

<p>(A) The purple diamond corresponds to the strongest associated SNP and the colour code indicates the linkage disequilibrium with respect to this variant. Horizontal lines indicate the -log₁₀ p-value such that the SNPs above the line are the potential causal ones. This set was defined based on a likelihood ratio for a particular SNP as being less or equal than 100, relative to the most likely variant and r²>0.1. (B) Haplotype block indicating relevant SNPs. From left to right the indicated SNPs correspond to: the strongest associated in <i>BRCA1/2</i> meta-analysis, the strongest in <i>BRCA1</i> and the strongest in <i>BRCA2</i>.</p

Conditional associations for <i>BRCA1</i> and <i>BRCA2</i> top SNPs.

<p><b>The table shows the HR estimate. 95% CI and p-value for the conditional analysis adjusting for the lead SNP in the univariate analysis for <i>BRCA1</i> (left hand side) or <i>BRCA2</i> mutation carriers (right had side).</b> SNPs correspond to: rs10124837, the strongest associated in <i>BRCA1</i>; rs62543583, the strongest associated in <i>BRCA2</i> mutation carriers; rs7046326, the strongest associated in <i>BRCA1/2</i> meta-analysis; rs3814113, was the strongest associated variant in the initial GWAS analysis. “HR”, hazard ratio; “CI”, confidence interval.</p