Genome Wide Association Studies in Small-Cell Lung Cancer. A Systematic Review

• Published in: Clinical lung cancer 2024-01, Vol.25 (1), p.9-17
• Main Authors: Ramón, Enjo-Barreiro José, Alberto, Ruano-Ravina, Mónica, Pérez-Ríos, Karl, Kelsey, Miguel, Barros-Dios Juan, Leonor, Varela-Lema
• Format: Article
• Language: English
• Subjects: Genome-Wide Association Study; Humans; Lung neoplasm; Lung Neoplasms - genetics; Nitrosamines; Small Cell Lung Carcinoma - genetics
• ISSN: 1525-7304; 1938-0690
• DOI: 10.1016/j.cllc.2023.10.002

•Small cell lung cancer (SCLC) is classified by key transcription regulators: ASCL1, NEURO1, and POU2F3.•A correlation was found between SNPs located in chromosome 15 and SCLC.•A correlation was found between the overexpression of ASCL1 and SCLC.•ASCL1 is the most common key transcription regulator associated with SCLC.•ASCL1 may regulate CHRNA5/A3/B4 gen cluster related with SCLC. Small cell lung cancer (SCLC) is one of the deadliest forms of lung cancer, but few information exists regarding the role of genetics, particularly on Genome Wide Association Studies (GWAS). The aim of the study is to explore the evidence available obtained through GWAS studies for SCLC using a systematic review. We performed a literature search in the main databases until July 31st, 2023. We included all human based studies on GWAS for lung cancer which presented results for SCLC. Only studies with participants diagnosed of SCLC with anatomopathological confirmation were included. Fourteen studies were identified; 8 studies showed a relationship between ASCL1 overexpression and SCLC, which may regulate CHRNA5/A3/B4 cluster, producing a consequent nAChR overexpression. Nine papers, including 8 of the previous, found a positive association between SNPs located in chromosome 15 and SCLC. The most important cluster of genes found is CHRNA5/A3/B4 but the mechanism for the role of these genes is unclear. Kyoto Encyclopaedia of Genes and Genome (KEGG) shows that these receptors were found to be overexpressed where nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N’-Nitrosonornicotine (NNN) acts, involving different routes in SCLC carcinogenesis.