Rare deleterious germline variants and risk of lung cancer

Rare deleterious germline variants and risk of lung cancer

Abstract Recent studies suggest that rare variants exhibit stronger effect sizes and might play a crucial role in the etiology of lung cancers (LC). Whole exome plus targeted sequencing of germline DNA was performed on 1045 LC cases and 885 controls in the discovery set. To unveil the inherited caus...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Yanhong Liu, Jun Xia, James McKay, Spiridon Tsavachidis, Xiangjun Xiao, Margaret R. Spitz, Chao Cheng, Jinyoung Byun, Wei Hong, Yafang Li, Dakai Zhu, Zhuoyi Song, Susan M. Rosenberg, Michael E. Scheurer, Farrah Kheradmand, Claudio W. Pikielny, Christine M. Lusk, Ann G. Schwartz, Ignacio I. Wistuba, Michael H. Cho, Edwin K. Silverman, Joan Bailey-Wilson, Susan M. Pinney, Marshall Anderson, Elena Kupert, Colette Gaba, Diptasri Mandal, Ming You, Mariza de Andrade, Ping Yang, Triantafillos Liloglou, Michael P. A. Davies, Jolanta Lissowska, Beata Swiatkowska, David Zaridze, Anush Mukeria, Vladimir Janout, Ivana Holcatova, Dana Mates, Jelena Stojsic, Ghislaine Scelo, Paul Brennan, Geoffrey Liu, John K. Field, Rayjean J. Hung, David C. Christiani, Christopher I. Amos
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
Materias:
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Acceso en línea:https://doaj.org/article/3431e92f9faa47b7bce60db50d9cfdaf
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
Descripción
Sumario:Abstract Recent studies suggest that rare variants exhibit stronger effect sizes and might play a crucial role in the etiology of lung cancers (LC). Whole exome plus targeted sequencing of germline DNA was performed on 1045 LC cases and 885 controls in the discovery set. To unveil the inherited causal variants, we focused on rare and predicted deleterious variants and small indels enriched in cases or controls. Promising candidates were further validated in a series of 26,803 LCs and 555,107 controls. During discovery, we identified 25 rare deleterious variants associated with LC susceptibility, including 13 reported in ClinVar. Of the five validated candidates, we discovered two pathogenic variants in known LC susceptibility loci, ATM p.V2716A (Odds Ratio [OR] 19.55, 95%CI 5.04–75.6) and MPZL2 p.I24M frameshift deletion (OR 3.88, 95%CI 1.71–8.8); and three in novel LC susceptibility genes, POMC c.*28delT at 3′ UTR (OR 4.33, 95%CI 2.03–9.24), STAU2 p.N364M frameshift deletion (OR 4.48, 95%CI 1.73–11.55), and MLNR p.Q334V frameshift deletion (OR 2.69, 95%CI 1.33–5.43). The potential cancer-promoting role of selected candidate genes and variants was further supported by endogenous DNA damage assays. Our analyses led to the identification of new rare deleterious variants with LC susceptibility. However, in-depth mechanistic studies are still needed to evaluate the pathogenic effects of these specific alleles.

Ejemplares similares