Multiple sequence alignment demonstrating phylogenetic conservation of the three biologically characterized phosphorylated BRCA2 residues affected by missense variants of unknown clinical significance.

<p>Multiple sequence alignment demonstrating phylogenetic conservation of the three biologically characterized phosphorylated BRCA2 residues affected by missense variants of unknown clinical significance.</p

NetworKIN analysis of BIC VUSs affecting biologically characterized phosphorylation motifs in BRCA1 and BRCA2.

<p>In <b>bold</b> are BRCA1 mutations that directly mutate an experimentally identified phosphorylation site. ^aThe position and change at the amino acids specified by the missense variant is as reported in the BIC database. ^bThe nucleotide change conforms to the HGVS nomenclature. ^cSNP IDs correspond to the dbSNP database <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062468#pone.0062468-Sherry1" target="_blank">[73]</a> SNP identifiers. ^dFrequency represents the number of times reported in the BIC database. ^eThe ten-residue long biologically uncharacterized kinase recognition motifs are shown. The biologically uncharacterized Serine (S), and threonine (T) residues shown to be phosphorylated by NetworKIN are underlined.</p

Figure 1

<p><b>a.</b> Summary of phosphorylation sites studied in BRCA1. Residues in green represent <i>in vivo</i> phosphorylation sites have been biologically characterized in the literature. Residues in red represent <i>in vivo</i> phosphorylation sites identified via throughput methods where biological functions have not yet been determined. <b>b.</b> Summary of phosphorylation sites studied in BRCA2. Residues in green represent <i>in vivo</i> phosphorylation sites that have been biologically characterized in the literature. Residues in red represent <i>in vivo</i> phosphorylation sites identified via throughput methods where biological functions have not yet been determined.</p

NetworKIN analysis of VUS affecting biologically uncharacterized phosphorylation sites in BRCA1 and BRCA2.

<p>In <b>bold</b> are BRCA1 mutations that fall within an experimentally identified but biologically uncharacterized phosphorylation site. ^aThe position and change at the amino acids specified by the missense variant is as reported in the BIC database. ^bThe nucleotide change conforms to the HGVS nomenclature. ^cSNP IDs correspond to the dbSNP database <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062468#pone.0062468-Sherry1" target="_blank">[73]</a> SNP identifiers. ^dFrequency represents the number of times reported in the BIC database. ^eThe ten-residue long biologically uncharacterized kinase recognition motifs are shown. The biologically uncharacterized Serine (S), and threonine (T) residues shown to be phosphorylated by NetworKIN are underlined. * Sites that retained a score but was considered to be “abolished” due to score falling below 5 with the presence of the VUS.</p

Forest plots of the odds ratios and confidence intervals of breast cancer associations in the homozygous model for (A) post-menopausal and (B) pre-menopausal women.

<p>Forest plots of the odds ratios and confidence intervals of breast cancer associations in the homozygous model for (A) post-menopausal and (B) pre-menopausal women.</p

Summary of Literature Search.

<p>Summary of Literature Search.</p

Characteristics of the studies of <i>MPO-G463A</i> polymorphism and its association with breast cancer stratified by menopausal status and antioxidant intake.

<p>Characteristics of the studies of <i>MPO-G463A</i> polymorphism and its association with breast cancer stratified by menopausal status and antioxidant intake.</p

Results of the meta-analysis for <i>MPO-G463A</i> polymorphism and breast cancer risk.

<p>OR (95% CI): odds ratio 95% confidence interval; P_het: P value for heterogeneity; Given that all P values for the heterogeneity test were >0.10, the fixed-effects model was used;</p>*<p>Bonferroni-corrected.</p

Characteristics of the studies of <i>MPO-G463A</i> polymorphism and its association with breast cancer according to menopausal status.

*<p>maf: minor allele frequency; HWE: Hardy-Weinberg equilibrium.</p

Characteristics of the studies of <i>MPO-G463A</i> polymorphism and its association with breast cancer stratified by antioxidant and vitamin-carotenoid intake.

<p>Characteristics of the studies of <i>MPO-G463A</i> polymorphism and its association with breast cancer stratified by antioxidant and vitamin-carotenoid intake.</p