2026-04-17T14:15:45Zhttps://recercat.cat/oai/request
oai:recercat.cat:2445/1267892025-11-20T15:01:47Zcom_2072_1057col_2072_478916col_2072_478917
RECERCAT author Bonifaci Cano, Núria author Gorski, Bohdan author Masojć, Bartlomiej author Wokolorczyk, Dominika author Jakubowska, Anna author Dębniak, Tadeusz author Berenguer, Antoni author Serra-Musach, Jordi author Brunet, Joan author Dopazo, Joaquín author Narod, Steven A. author Lubinski, Jan author Lázaro García, Conxi author Cybulski, Cezary author Pujana Genestar, M. Ángel 2018-12-07T11:53:21Z2018-12-07T11:53:21Z2010-11-222018-07-24T13:02:47Z Recent genome-wide association studies (GWASs) have identified candidate genes contributing to cancer risk through low-penetrance mutations. Many of these genes were unexpected and, intriguingly, included well-known players in carcinogenesis at the somatic level. To assess the hypothesis of a germline-somatic link in carcinogenesis, we evaluated the distribution of somatic gene labels within the ordered results of a breast cancer risk GWAS. This analysis suggested frequent influence on risk of genetic variation in loci encoding for "driver kinases" (i.e., kinases encoded by genes that showed higher somatic mutation rates than expected by chance and, therefore, whose deregulation may contribute to cancer development and/or progression). Assessment of these predictions using a population-based case-control study in Poland replicated the association for rs3732568 in EPHB1 (odds ratio (OR) = 0.79; 95% confidence interval (CI): 0.63-0.98; P-trend = 0.031). Analyses by early age at diagnosis and by estrogen receptor alpha (ER alpha) tumor status indicated potential associations for rs6852678 in CDKL2 (OR = 0.32, 95% CI: 0.10-1.00; P-recessive = 0.044) and rs10878640 in DYRK2 (OR = 2.39, 95% CI: 1.32-4.30; P-dominant = 0.003), and for rs12765929, rs9836340, rs4707795 in BMPR1A, EPHA3 and EPHA7, respectively (ER alpha tumor status P-interaction<0.05). The identification of three novel candidates as EPH receptor genes might indicate a link between perturbed compartmentalization of early neoplastic lesions and breast cancer risk and progression. Together, these data may lay the foundations for replication in additional populations and could potentially increase our knowledge of the underlying molecular mechanisms of breast carcinogenesis. cc by (c) Bonifaci et al., 2010 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Càncer de mama Carcinogènesi Breast cancer Carcinogenesis Exploring the Link Between Germline and Somatic Genetic Alterations in Breast Carcinogenesis info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion