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

José Ramón Enjo-Barreiro; Alberto Ruano-Ravina; Mónica Pérez-Ríos; Karl Kelsey; Juan Miguel Barros-Dios; Leonor Varela-Lema

doi:10.1016/j.cllc.2023.10.002

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

Clin Lung Cancer. 2024 Jan;25(1):9-17. doi: 10.1016/j.cllc.2023.10.002. Epub 2023 Oct 12.

Authors

José Ramón Enjo-Barreiro¹, Alberto Ruano-Ravina², Mónica Pérez-Ríos³, Karl Kelsey⁴, Juan Miguel Barros-Dios³, Leonor Varela-Lema³

Affiliations

¹ Department of Preventive Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain; Service of Preventive Medicine, A Coruña University Teaching Hospital Complex, A Coruña, Spain.
² Department of Preventive Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Santiago de Compostela, Spain; Health Research Institute of Santiago de Compostela (Instituto de Investigación Sanitaria de Santiago de Compostela - IDIS), Santiago de Compostela, Spain. Electronic address: alberto.ruano@usc.es.
³ Department of Preventive Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Santiago de Compostela, Spain; Health Research Institute of Santiago de Compostela (Instituto de Investigación Sanitaria de Santiago de Compostela - IDIS), Santiago de Compostela, Spain.
⁴ Department of Epidemiology, Brown School of Public Health, Brown University, Providence, RI.

PMID: 37940411
DOI: 10.1016/j.cllc.2023.10.002

Abstract

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.

Keywords: ASCL1; CHRNA5/A3/B4; Lung neoplasm; Oncogenes; Small-cell lung carcinoma.

Publication types

Systematic Review
Research Support, Non-U.S. Gov't

MeSH terms

Genome-Wide Association Study
Humans
Lung Neoplasms* / genetics
Nitrosamines*
Small Cell Lung Carcinoma* / genetics

Substances

N'-nitrosonornicotine
Nitrosamines