Mosaic chromosomal alterations is associated with increased lung cancer risk: insight from the INTEGRAL-ILCCO cohort analysis.

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Cheng, Chao, Hong, Wei, Li, Yafang, Xiao, Xiangjun, McKay, James, Han, Younghun, Byun, Jinyoung, Peng, Bo, Albanes, Demetrios, Lam, Stephen et al (show 37 more authors) , Tardon, Adonina, Chen, Chu, Bojesen, Stig E, Landi, Maria T, Johansson, Mattias, Risch, Angela, Bickeböller, Heike, Wichmann, H-Erich, Christiani, David C, Rennert, Gad, Arnold, Susanne, Goodman, Gary, Field, John K ORCID: 0000-0003-3951-6365, Davies, Michael Pa ORCID: 0000-0002-7609-4977, Shete, Sanjay S, Le Marchand, Loic, Liu, Geoffrey, Hung, Rayjean J, Andrew, Angeline S, Kiemeney, Lambertus A, Zhu, Meng, Shen, Hongbing, Zienolddiny, Shan, Grankvist, Kjell, Johansson, Mikael, Cox, Angela, Hong, Yun-Chul, Yuan, Jian-Min, Lazarus, Philip, Schabath, Matthew B, Aldrich, Melinda C, Brennan, Paul, Li, Yong, Gorlova, Olga, Gorlov, Ivan, Amos, Christopher I and INTEGRAL-ILCCO lung cancer consortium, (2023) Mosaic chromosomal alterations is associated with increased lung cancer risk: insight from the INTEGRAL-ILCCO cohort analysis. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 18 (8). S1556-0864(23)00527-0-S1556-0864(23)00527-0.

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Abstract

Mosaic chromosomal alterations (mCAs) detected in white blood cells represent a type of clonal hematopoiesis (CH) that is understudied compared to CH-related somatic mutations. A few recent studies indicated their potential link with non-hematological 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 (CN-LOH) on autosomal chromosomes. The association between autosome CN-LOH and increased risk of lung cancer was further confirmed in two major histological subtypes, lung adenocarcinoma and squamous cell carcinoma. Additionally, we observed a significant increase of ChrX mCAs and mChrY losses in smokers compared to non-smokers, 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.

Item Type:	Article
Uncontrolled Keywords:	INTEGRAL-ILCCO lung cancer consortium
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	15 May 2023 08:12
Last Modified:	24 Aug 2023 04:59
DOI:	10.1016/j.jtho.2023.05.001
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3170278