Workflow of miRNA SNP selection.

<p>Workflow of miRNA SNP selection.</p

Association of rs2046210 with breast cancer in Asian ER

<p>−<b>*versus ER+**cases and controls.</b> *Estrogen receptor negative; **Estrogen receptor positive.</p

Association of rs2046210 and rs12662670 with breast cancer.

<p>Results are presented overall and separately for Europeans and Asians. Pooled analyses adjusted for study only as well as adjusted for rs12662670 or rs2046210, respectively, in addition to study were performed.</p>a<p>P-value derived from the log-additive model.</p>b<p>Odds ratio per minor allele (A allele for rs2046210, G allele for rs12662670).</p>c<p>Odds ratio relative to the major allele homozygous (GT) genotype.</p

The 42 studied SNPs in miRNAs, miRNA machinery genes and miRNA target genes.

<p>Tag SNPs used in the analysis are presented in the parenthesis along with the R squred value relative to the functional SNP.</p>a<p>According to Patrocles prediction; AC  =  abolishes conserved binding site, ANC  =  abolishes non-conserved binding site, CNC  =  creates non-conserved binding site (Target sites are considered conserved if they are shared by at least one primate, one rodent and one nonprimate/nonrodent mammal <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109973#pone.0109973-Hiard1" target="_blank">[24]</a>).</p><p>The 42 studied SNPs in miRNAs, miRNA machinery genes and miRNA target genes.</p

Association of rs2046210 with breast cancer in European ER

<p>−<b>*versus ER+*cases and controls.</b> *Estrogen receptor negative; **Estrogen receptor positive.</p

Association of rs12662670 with breast cancer in Europeans versus Asians.

<p>Association of rs12662670 with breast cancer in Europeans versus Asians.</p

Association of rs12662670 with breast cancer in European ER

<p>−<b>*versus ER+**cases and controls.</b> *Estrogen receptor negative; **Estrogen receptor positive.</p

Linkage disequilibrium blocks in the <i>ESR1</i> region.

<p>Five SNPs tagged (at r2>0.9) by rs12662670 and three by rs2046210 are marked by arrows (dark and light grey respectively); rs12662670 and rs2046210 are marked by stars; rs3757318 and rs9397435 are marked by points; blocks were generated using data from the 1000 Genomes Project and HapMap; blocks include all single nucleotide polymorphisms with a minor allele frequency >0.05. The directions of translation of <i>ESR1</i> and <i>C6orf97</i> are marked and other genes in the locus are listed.</p

Association of haplotypes composed of rs2046210 and rs12662670 with breast cancer.

<p>Results are presented overall and separately for Europeans and Asians. Pooled analyses adjusted for study were performed.</p>a<p>Odds ratio per haplotype compared to the reference haplotype (i.e., the most frequent haplotype).</p>b<p>P-value derived from the log-additive model.</p>c<p>Minor allele.</p>d<p>Reference haplotype.</p

Association of rs2046210 and rs12662670 with risk of ER−^*/ER+^** breast cancer.

<p>Results are presented overall as well as separately for Europeans and Asians. Pooled analyses adjusted for the studies were performed. A log-additive genetic model was assumed.</p>*<p>Estrogen receptor negative.</p>**<p>Estrogen receptor positive.</p>a<p>Odds ratio per minor allele (A allele for rs2046210, G allele for rs12662670) derived from case-control logistic regression restricted to ER+ or ER− cases, respectively, and the whole control sample.</p>b<p>P-value derived from the log-additive model derived from case-control logistic regression restricted to ER+ or ER− cases, respectively, and the whole control sample.</p>c<p>P-value for heterogeneity between estimates of genetic main effects derived from case-only analysis.</p