Genome-wide interaction analysis identified low-frequency variants with sex disparity in lung cancer risk.
Journal
Human molecular genetics
ISSN: 1460-2083
Titre abrégé: Hum Mol Genet
Pays: England
ID NLM: 9208958
Informations de publication
Date de publication:
23 08 2022
23 08 2022
Historique:
received:
06
08
2021
revised:
14
01
2022
accepted:
31
01
2022
pubmed:
10
2
2022
medline:
27
8
2022
entrez:
9
2
2022
Statut:
ppublish
Résumé
Differences by sex in lung cancer incidence and mortality have been reported which cannot be fully explained by sex differences in smoking behavior, implying existence of genetic and molecular basis for sex disparity in lung cancer development. However, the information about sex dimorphism in lung cancer risk is quite limited despite the great success in lung cancer association studies. By adopting a stringent two-stage analysis strategy, we performed a genome-wide gene-sex interaction analysis using genotypes from a lung cancer cohort including ~ 47 000 individuals with European ancestry. Three low-frequency variants (minor allele frequency < 0.05), rs17662871 [odds ratio (OR) = 0.71, P = 4.29×10-8); rs79942605 (OR = 2.17, P = 2.81×10-8) and rs208908 (OR = 0.70, P = 4.54×10-8) were identified with different risk effect of lung cancer between men and women. Further expression quantitative trait loci and functional annotation analysis suggested rs208908 affects lung cancer risk through differential regulation of Coxsackie virus and adenovirus receptor gene expression in lung tissues between men and women. Our study is one of the first studies to provide novel insights about the genetic and molecular basis for sex disparity in lung cancer development.
Identifiants
pubmed: 35138370
pii: 6524820
doi: 10.1093/hmg/ddac030
pmc: PMC9402242
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2831-2843Subventions
Organisme : NCI NIH HHS
ID : R35 CA197449
Pays : United States
Organisme : NCI NIH HHS
ID : U19 CA203654
Pays : United States
Organisme : NIEHS NIH HHS
ID : R24 ES028527
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA167462
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA235464
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES030285
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA015083
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA243483
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA167462
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA076292
Pays : United States
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press.
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