A rare FGF5 candidate variant (rs112475347) for predisposition to nonsquamous, nonsmall‐cell lung cancer

作者：Lisa Cannon‐Albright, Craig C. Teerlink, Jeff Stevens, Julio C. Facelli, Shamus R. Carr, Kristina Allen‐Brady, Sonam Puri, Joan E. Bailey‐Wilson, Anthony M. Musolf, Wallace Akerley · 发表于：International Journal of Cancer · 年份：2023 · DOI：10.1002/ijc.34510 · 被引用次数：3 · 研究领域：Fibroblast Growth Factor Research、Epigenetics and DNA Methylation、Lung Cancer Treatments and Mutations

Abstract A unique approach with rare resources was used to identify candidate variants predisposing to familial nonsquamous nonsmall‐cell lung cancers (NSNSCLC). We analyzed sequence data from NSNSCLC‐affected cousin pairs belonging to high‐risk lung cancer pedigrees identified in a genealogy of Utah linked to statewide cancer records to identify rare, shared candidate predisposition variants. Variants were tested for association with lung cancer risk in UK Biobank. Evidence for linkage with lung cancer was also reviewed in families from the Genetic Epidemiology of Lung Cancer Consortium. Protein prediction modeling compared the mutation with reference. We sequenced NSNSCLC‐affected cousin pairs from eight high‐risk lung cancer pedigrees and identified 66 rare candidate variants shared in the cousin pairs. One variant in the FGF5 gene also showed significant association with lung cancer in UKBiobank. This variant was observed in 3/163 additional sampled Utah lung cancer cases, 2 of whom were related in another independent pedigree. Modeling of the predicted protein predicted a second binding site for SO 4 that may indicate binding differences. This unique study identified multiple candidate predisposition variants for NSNSCLC, including a rare variant in FGF5 that was significantly associated with lung cancer risk and that segregated with lung cancer in the two pedigrees in which it was observed. FGF5 is an oncogenic factor in several human cancers, and the mutation found her...