Mosaic chromosomal alterations is associated with increased lung cancer risk: insight from the INTEGRAL-ILCCO cohort analysis.
Publication Title
J Thorac Oncol
Document Type
Article
Publication Date
5-5-2023
Keywords
washington; swedish cancer; Clonal hematopoiesis; Lung cancer risk; Mosaic chromosomal alterations
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
Clinical Institute
Cancer
Specialty/Research Institute
Oncology
Specialty/Research Institute
Pulmonary Medicine
DOI
10.1016/j.jtho.2023.05.001
