Evaluating genetic variants associated with breast cancer risk in high and moderate-penetrance genes in Asians

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Over the past 20 years, high-penetrance pathogenic mutations in genes <span style="font-style:italic;">BRCA1</span>, <span style="font-style:italic;">BRCA2</span>, <span style="font-style:italic;">TP53</span>, <span style="font-style:italic;">PTEN</span>, <span style="font-style:italic;">STK11</span> and <span style="font-style:italic;">CDH1</span> and moderate-penetrance mutations in genes <span style="font-style:italic;">CHEK2, ATM, BRIP1, PALB2</span>, <span style="font-style:italic;">RAD51C, RAD50</span> and <span style="font-style:italic;">NBN</span> have been identified for breast cancer. In this study, we investigated whether there are additional variants in these 13 genes associated with breast cancer among women of Asian ancestry. We analyzed up to 654 single nucleotide polymorphisms (SNPs) from 6269 cases and 6624 controls of Asian descent included in the Breast Cancer Association Consortium (BCAC), and up to 236 SNPs from 5794 cases and 5529 controls included in the Shanghai Breast Cancer Genetics Study (SBCGS). We found three missense variants with minor allele frequency (MAF) <0.05: rs80358978 (Gly2508Ser), rs80359065 (Lys2729Asn) and rs11571653 (Met784Val) in the <span style="font-style:italic;">BRCA2</span> gene, showing statistically significant associations with breast cancer risk, with <span style="font-style:italic;">P</span>-values of 1.2 × 10^–4, 1.0 × 10^–3 and 5.0 × 10^–3, respectively. In addition, we found four low-frequency variants (rs8176085, rs799923, rs8176173 and rs8176258) in the <span style="font-style:italic;">BRCA1</span> gene, one common variant in the <span style="font-style:italic;">CHEK2</span> gene (rs9620817), and one common variant in the <span style="font-style:italic;">PALB2</span> gene (rs13330119) associated with breast cancer risk at <span style="font-style:italic;">P</span> < 0.01. Our study identified several new risk variants in <span style="font-style:italic;">BRCA1</span>, <span style="font-style:italic;">BRCA2, CHEK2,</span> and <span style="font-style:italic;">PALB2</span> genes in relation to breast cancer risk in Asian women. These results provide further insights that, in addition to the high/moderate penetrance mutations, other low-penetrance variants in these genes may also contribute to breast cancer risk.</span>

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2phzY0H
via IFTTT