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BRCA1/2-negative, high-risk breast cancers (BRCAX) for Asian women: genetic susceptibility loci and their potential impacts

“BRCAX” refers breast cancers occurring in women with a family history predictive of being a BRCA1/2 mutation carrier, but BRCA1/2 genetic screening has failed to find causal mutations. In this study, we report the findings of the genetic architecture of BRCAX with novel and redefined candidate loci...

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Autores principales: Lee, Joo-Yeon, Kim, Jisun, Kim, Sung-Won, Park, Sue K., Ahn, Sei Hyun, Lee, Min Hyuk, Suh, Young Jin, Noh, Dong-Young, Son, Byung Ho, Cho, Young Up, Lee, Sae Byul, Lee, Jong Won, Hopper, John L., Sung, Joohon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189145/
https://www.ncbi.nlm.nih.gov/pubmed/30323354
http://dx.doi.org/10.1038/s41598-018-31859-8
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author Lee, Joo-Yeon
Kim, Jisun
Kim, Sung-Won
Park, Sue K.
Ahn, Sei Hyun
Lee, Min Hyuk
Suh, Young Jin
Noh, Dong-Young
Son, Byung Ho
Cho, Young Up
Lee, Sae Byul
Lee, Jong Won
Hopper, John L.
Sung, Joohon
author_facet Lee, Joo-Yeon
Kim, Jisun
Kim, Sung-Won
Park, Sue K.
Ahn, Sei Hyun
Lee, Min Hyuk
Suh, Young Jin
Noh, Dong-Young
Son, Byung Ho
Cho, Young Up
Lee, Sae Byul
Lee, Jong Won
Hopper, John L.
Sung, Joohon
author_sort Lee, Joo-Yeon
collection PubMed
description “BRCAX” refers breast cancers occurring in women with a family history predictive of being a BRCA1/2 mutation carrier, but BRCA1/2 genetic screening has failed to find causal mutations. In this study, we report the findings of the genetic architecture of BRCAX with novel and redefined candidate loci and their potential impacts on preventive strategy. We performed a genome-wide association study involving 1,469 BRCAX cases from the Korean Hereditary Breast Cancer study, and high-risk breast cancer cases (1,482 Asians and 9,902 Europeans) from the Breast Cancer Association Consortium. We also evaluated the previously reported susceptibility loci for their roles in the high-risk breast cancers. We have identified three novel loci (PDE7B, UBL3, and a new independent marker in CDKN2B-AS1) associated with BRCAX, and replicated previously reported SNPs (24 of 92) and moderate/high-penetrance (seven of 23) genes for Korean BRCAX. For the novel candidate loci, evidence supported their roles in regulatory function. We estimated that the common low-penetrance loci might explain a substantial part of high-risk breast cancer (39.4% for Koreans and 24.0% for Europeans). Our study findings suggest that common genetic markers with lower penetrance constitute a part of susceptibility to high-risk breast cancers, with potential implications for a more comprehensive genetic screening test.
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spelling pubmed-61891452018-10-22 BRCA1/2-negative, high-risk breast cancers (BRCAX) for Asian women: genetic susceptibility loci and their potential impacts Lee, Joo-Yeon Kim, Jisun Kim, Sung-Won Park, Sue K. Ahn, Sei Hyun Lee, Min Hyuk Suh, Young Jin Noh, Dong-Young Son, Byung Ho Cho, Young Up Lee, Sae Byul Lee, Jong Won Hopper, John L. Sung, Joohon Sci Rep Article “BRCAX” refers breast cancers occurring in women with a family history predictive of being a BRCA1/2 mutation carrier, but BRCA1/2 genetic screening has failed to find causal mutations. In this study, we report the findings of the genetic architecture of BRCAX with novel and redefined candidate loci and their potential impacts on preventive strategy. We performed a genome-wide association study involving 1,469 BRCAX cases from the Korean Hereditary Breast Cancer study, and high-risk breast cancer cases (1,482 Asians and 9,902 Europeans) from the Breast Cancer Association Consortium. We also evaluated the previously reported susceptibility loci for their roles in the high-risk breast cancers. We have identified three novel loci (PDE7B, UBL3, and a new independent marker in CDKN2B-AS1) associated with BRCAX, and replicated previously reported SNPs (24 of 92) and moderate/high-penetrance (seven of 23) genes for Korean BRCAX. For the novel candidate loci, evidence supported their roles in regulatory function. We estimated that the common low-penetrance loci might explain a substantial part of high-risk breast cancer (39.4% for Koreans and 24.0% for Europeans). Our study findings suggest that common genetic markers with lower penetrance constitute a part of susceptibility to high-risk breast cancers, with potential implications for a more comprehensive genetic screening test. Nature Publishing Group UK 2018-10-15 /pmc/articles/PMC6189145/ /pubmed/30323354 http://dx.doi.org/10.1038/s41598-018-31859-8 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Lee, Joo-Yeon
Kim, Jisun
Kim, Sung-Won
Park, Sue K.
Ahn, Sei Hyun
Lee, Min Hyuk
Suh, Young Jin
Noh, Dong-Young
Son, Byung Ho
Cho, Young Up
Lee, Sae Byul
Lee, Jong Won
Hopper, John L.
Sung, Joohon
BRCA1/2-negative, high-risk breast cancers (BRCAX) for Asian women: genetic susceptibility loci and their potential impacts
title BRCA1/2-negative, high-risk breast cancers (BRCAX) for Asian women: genetic susceptibility loci and their potential impacts
title_full BRCA1/2-negative, high-risk breast cancers (BRCAX) for Asian women: genetic susceptibility loci and their potential impacts
title_fullStr BRCA1/2-negative, high-risk breast cancers (BRCAX) for Asian women: genetic susceptibility loci and their potential impacts
title_full_unstemmed BRCA1/2-negative, high-risk breast cancers (BRCAX) for Asian women: genetic susceptibility loci and their potential impacts
title_short BRCA1/2-negative, high-risk breast cancers (BRCAX) for Asian women: genetic susceptibility loci and their potential impacts
title_sort brca1/2-negative, high-risk breast cancers (brcax) for asian women: genetic susceptibility loci and their potential impacts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189145/
https://www.ncbi.nlm.nih.gov/pubmed/30323354
http://dx.doi.org/10.1038/s41598-018-31859-8
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