Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Spain.
Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública - CIBERESP), Spain; Health Research Institute of Santiago de Compostela (Instituto de Investigación Sanitaria de Santiago de Compostela - IDIS), Santiago de Compostela, Spain.
Arch Bronconeumol. 2023 Oct;59(10):645-650. doi: 10.1016/j.arbres.2023.07.008. Epub 2023 Jul 15.
Small cell lung cancer (SCLC) comprises 10-15% of all lung cancer cases and is the most aggressive histological type. Survival is poor and the molecular landscape of this disease is extraordinarily complex. The objective of this paper was to perform a Genome-Wide Association Study (GWAS) of this disease using a case-control study specifically designed for small cell lung cancer (SCLC).
Incident cases were consecutively recruited from 8 hospitals from different regions of Spain. Controls were recruited from the same hospitals using a frequency sampling based on age and sex distribution of cases. Biological samples were obtained along with detailed information on cases and controls lifestyle, including tobacco and radon exposure.
We included 271 SCLC cases and 557 controls. We found evidence (p-values<10) of an association in the complete dataset for several loci, while MAP4 showed a significant association in the gene-based analysis. Pathway analysis suggested that ATR, ATRIP, MCM4, MCM5, ORC4, RPA3 and CDC25A genes have a role on the onset of SCLC.
This study provides biological evidence for pathways related to SCLC, offering novel loci for further research.
小细胞肺癌（SCLC）占所有肺癌病例的 10-15%，是最具侵袭性的组织学类型。患者的存活率很低，且该疾病的分子图谱异常复杂。本文旨在使用专门针对小细胞肺癌（SCLC）设计的病例对照研究，对该疾病进行全基因组关联研究（GWAS）。
连续从西班牙 8 家不同地区的医院招募了新发病例。对照是根据病例的年龄和性别分布，在相同的医院通过频率抽样招募的。在获得病例和对照的详细生活方式信息（包括烟草和氡暴露）的同时，还采集了生物样本。
我们纳入了 271 例 SCLC 病例和 557 例对照。在完整数据集的分析中，我们发现了几个与 SCLC 相关的显著关联（p 值<10），而在基因层面的分析中，MAP4 表现出显著的关联。通路分析表明，ATR、ATRIP、MCM4、MCM5、ORC4、RPA3 和 CDC25A 基因在 SCLC 的发病机制中起作用。
本研究为 SCLC 相关通路提供了生物学证据，为进一步研究提供了新的候选基因。
