Mosaic Chromosomal Alterations Are Associated With Increased Lung Cancer Risk: Insight From the INTEGRAL-ILCCO Cohort Analysis.
Clonal hematopoiesis
Loss of heterozygosity
Lung cancer risk
Mosaic chromosomal alterations
Journal
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
ISSN: 1556-1380
Titre abrégé: J Thorac Oncol
Pays: United States
ID NLM: 101274235
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
14
03
2023
revised:
21
04
2023
accepted:
01
05
2023
pmc-release:
01
08
2024
medline:
24
7
2023
pubmed:
8
5
2023
entrez:
7
5
2023
Statut:
ppublish
Résumé
Mosaic chromosomal alterations (mCAs) detected in white blood cells represent a type of clonal hematopoiesis (CH) that is understudied compared with CH-related somatic mutations. A few recent studies indicated their potential link with nonhematological cancers, especially lung cancer. In this study, we investigated the association between mCAs and lung cancer using the high-density genotyping data from the OncoArray study of INTEGRAL-ILCCO, the largest single genetic study of lung cancer with 18,221 lung cancer cases and 14,825 cancer-free controls. We identified a comprehensive list of autosomal mCAs, ChrX mCAs, and mosaic ChrY (mChrY) losses from these samples. Autosomal mCAs were detected in 4.3% of subjects, in addition to ChrX mCAs in 3.6% of females and mChrY losses in 9.6% of males. Multivariable logistic regression analysis indicated that the presence of autosomal mCAs in white blood cells was associated with an increased lung cancer risk after adjusting for key confounding factors, including age, sex, smoking status, and race. This association was mainly driven by a specific type of mCAs: copy-neutral loss of heterozygosity on autosomal chromosomes. The association between autosome copy-neutral loss of heterozygosity and increased risk of lung cancer was further confirmed in two major histologic subtypes, lung adenocarcinoma and squamous cell carcinoma. In addition, we observed a significant increase of ChrX mCAs and mChrY losses in smokers compared with nonsmokers and racial differences in certain types of mCA events. Our study established a link between mCAs in white blood cells and increased risk of lung cancer.
Identifiants
pubmed: 37150255
pii: S1556-0864(23)00527-0
doi: 10.1016/j.jtho.2023.05.001
pmc: PMC10435278
mid: NIHMS1922894
pii:
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
1003-1016Subventions
Organisme : NCI NIH HHS
ID : P30 CA076292
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA269764
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA227996
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000445
Pays : United States
Informations de copyright
Copyright © 2023. Published by Elsevier Inc.
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