Study-adjusted association between SNP rs2180341 and breast cancer risk by age among cases and controls of European ancestry, Breast Cancer Association Consortium (BCAC).

<p>Study-adjusted association between SNP rs2180341 and breast cancer risk by age among cases and controls of European ancestry, Breast Cancer Association Consortium (BCAC).</p

Adjusted¹, weighted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between SNP rs2180341 genotype and breast cancer risk, in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).²

1<p>Adjusted for birth year and study.</p>2<p>Restricted to women of European descent.</p>3<p>MAF = Minor allele frequency.</p

Forest plot of SNP rs2180341 per-allele odds ratios (ORs) and 95% confidence intervals (CIs) with the risk of breast cancer among studies from Breast Cancer Association Consortium (BCAC) breast cancer cases and controls of European ancestry.

<p>Studies are weighted and ranked according to the inverse of the between-study and within study variation of the log odds ratio, which is also represented by the size of the shaded box around the study-specific point estimate. The solid line indicates the OR = 1 and the dashed lined indicates the summary OR of all studies. A description of the study acronyms can be found in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035706#pone.0035706.s001" target="_blank">Supporting Information S1</a>.</p

Association between SNP rs2180341 and breast cancer risk by estrogen receptor (ER) status among cases and controls of European ancestry, Breast Cancer Association Consortium (BCAC).

<p>Association between SNP rs2180341 and breast cancer risk by estrogen receptor (ER) status among cases and controls of European ancestry, Breast Cancer Association Consortium (BCAC).</p

SNP rs2180341 per-allele hazard ratios (HRs) and 95% confidence intervals (CIs) among Consortium of Investigators of Modifiers of <i>BRCA1/2</i> (CIMBA) in A. <i>BRCA1</i> mutation carriers B. <i>BRCA2</i> mutation carriers.

<p>Studies are weighted and ranked according to the inverse of the between-study and within study variation of the log odds ratio, which is also represented by the size of the shaded box around the study-specific point estimate. The solid line indicates the OR = 1 and the dashed lined indicates the summary OR of all studies. A description of the study acronyms can be found in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035706#pone.0035706.s001" target="_blank">Supporting Information S1</a>.</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

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 <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

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