Mosaic Chromosomal Alterations Are Associated With Increased Lung Cancer Risk: Insight From the INTEGRAL-ILCCO Cohort Analysis
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Introduction: 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. Methods: 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. Results: 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. Conclusions: Our study established a link between mCAs in white blood cells and increased risk of lung cancer.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Journal of Thoracic Oncology |
| Vol/bind | 18 |
| Udgave nummer | 8 |
| Sider (fra-til) | 1003-1016 |
| Antal sider | 14 |
| ISSN | 1556-0864 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
This study is supported by the Cancer Prevention Research Institute of Texas (RR180061 to Dr. Cheng and RR170048 to Dr. Amos), the National Cancer Institute of the National Institutes of Health (1R01CA269764 to Dr. Cheng), and the National Natural Science Foundation of China (81820108028 to Dr. Shen). Dr. Cheng and Dr. Amos are Cancer Prevention Research Institute of Texas Scholars in Cancer Research. Vanderbilt University Medical Center’s BioVU is supported by institutional funding and by the Vanderbilt CTSA grant UL1 TR000445 from the National Center for Advancing Translational Sciences of the National Institutes of Health. Where authors are identified as personnel of the International Agency for Research on Cancer/WHO, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/WHO.
Funding Information:
This study is supported by the Cancer Prevention Research Institute of Texas (RR180061 to Dr. Cheng and RR170048 to Dr. Amos), the National Cancer Institute of the National Institutes of Health (1R01CA269764 to Dr. Cheng), and the National Natural Science Foundation of China (81820108028 to Dr. Shen). Dr. Cheng and Dr. Amos are Cancer Prevention Research Institute of Texas Scholars in Cancer Research. Vanderbilt University Medical Center's BioVU is supported by institutional funding and by the Vanderbilt CTSA grant UL1 TR000445 from the National Center for Advancing Translational Sciences of the National Institutes of Health. Where authors are identified as personnel of the International Agency for Research on Cancer/WHO, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/WHO.
Publisher Copyright:
© 2023
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