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Deciphering associations between three RNA splicing-related genetic variants and lung cancer risk.

Publication ,  Journal Article
Yang, W; Liu, H; Zhang, R; Freedman, JA; Han, Y; Hung, RJ; Brhane, Y; McLaughlin, J; Brennan, P; Bickeboeller, H; Rosenberger, A; Houlston, RS ...
Published in: NPJ Precis Oncol
June 30, 2022
Published version (DOI) Link to item

Limited efforts have been made in assessing the effect of genome-wide profiling of RNA splicing-related variation on lung cancer risk. In the present study, we first identified RNA splicing-related genetic variants linked to lung cancer in a genome-wide profiling analysis and then conducted a two-stage (discovery and replication) association study in populations of European ancestry. Discovery and validation were conducted sequentially with a total of 29,266 cases and 56,450 controls from both the Transdisciplinary Research in Cancer of the Lung and the International Lung Cancer Consortium as well as the OncoArray database. For those variants identified as significant in the two datasets, we further performed stratified analyses by smoking status and histological type and investigated their effects on gene expression and potential regulatory mechanisms. We identified three genetic variants significantly associated with lung cancer risk: rs329118 in JADE2 (P = 8.80E-09), rs2285521 in GGA2 (P = 4.43E-08), and rs198459 in MYRF (P = 1.60E-06). The combined effects of all three SNPs were more evident in lung squamous cell carcinomas (P = 1.81E-08, P = 6.21E-08, and P = 7.93E-04, respectively) than in lung adenocarcinomas and in ever smokers (P = 9.80E-05, P = 2.70E-04, and P = 2.90E-05, respectively) than in never smokers. Gene expression quantitative trait analysis suggested a role for the SNPs in regulating transcriptional expression of the corresponding target genes. In conclusion, we report that three RNA splicing-related genetic variants contribute to lung cancer susceptibility in European populations. However, additional validation is needed, and specific splicing mechanisms of the target genes underlying the observed associations also warrants further exploration.

Duke Scholars

Jennifer Freedman
Author Jennifer Freedman Medicine, Medical Oncology
Steven Patierno
Author Steven Patierno Medicine, Medical Oncology
Qingyi Wei
Author Qingyi Wei Population Health Sciences
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Published In

NPJ Precis Oncol

DOI

10.1038/s41698-022-00281-9

ISSN

2397-768X

Publication Date

June 30, 2022

Volume

6

Issue

1

Start / End Page

48

Location

England

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 3204 Immunology
 

Citation

APA
Chicago
ICMJE
MLA
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Yang, W., Liu, H., Zhang, R., Freedman, J. A., Han, Y., Hung, R. J., … Wei, Q. (2022). Deciphering associations between three RNA splicing-related genetic variants and lung cancer risk. NPJ Precis Oncol, 6(1), 48. https://doi.org/10.1038/s41698-022-00281-9
Yang, Wenjun, Hongliang Liu, Ruoxin Zhang, Jennifer A. Freedman, Younghun Han, Rayjean J. Hung, Yonathan Brhane, et al. “Deciphering associations between three RNA splicing-related genetic variants and lung cancer risk.” NPJ Precis Oncol 6, no. 1 (June 30, 2022): 48. https://doi.org/10.1038/s41698-022-00281-9.
Yang W, Liu H, Zhang R, Freedman JA, Han Y, Hung RJ, et al. Deciphering associations between three RNA splicing-related genetic variants and lung cancer risk. NPJ Precis Oncol. 2022 Jun 30;6(1):48.
Yang, Wenjun, et al. “Deciphering associations between three RNA splicing-related genetic variants and lung cancer risk.” NPJ Precis Oncol, vol. 6, no. 1, June 2022, p. 48. Pubmed, doi:10.1038/s41698-022-00281-9.
Yang W, Liu H, Zhang R, Freedman JA, Han Y, Hung RJ, Brhane Y, McLaughlin J, Brennan P, Bickeboeller H, Rosenberger A, Houlston RS, Caporaso NE, Landi MT, Brueske I, Risch A, Christiani DC, Amos CI, Chen X, Patierno SR, Wei Q. Deciphering associations between three RNA splicing-related genetic variants and lung cancer risk. NPJ Precis Oncol. 2022 Jun 30;6(1):48.

Published In

NPJ Precis Oncol

DOI

10.1038/s41698-022-00281-9

ISSN

2397-768X

Publication Date

June 30, 2022

Volume

6

Issue

1

Start / End Page

48

Location

England

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 3204 Immunology