Association of autosomal mosaic chromosomal alterations with risk of bladder cancer in Chinese adults: a prospective cohort study

Little is known about the prospective association between autosomal mosaic chromosomal alterations (mCAs), a group of large-scale somatic mutations on autosomes, and bladder cancer. Here we utilized data from 99,877 participants who were free of physician-diagnosed cancer at baseline (2004–2008) of...

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Main Authors: Song, M, Han, Y, Zhao, Y, Lv, J, Yu, C, Pei, P, Yang, L, Millwood, IY, Walters, RG, Chen, Y, Du, H, Yang, X, Yao, W, Chen, J, Chen, Z, Genovese, G, Terao, C, Li, L, Sun, D
Format: Journal article
Language:English
Published: Springer Nature [academic journals on nature.com] 2024
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author Song, M
Han, Y
Zhao, Y
Lv, J
Yu, C
Pei, P
Yang, L
Millwood, IY
Walters, RG
Chen, Y
Du, H
Yang, X
Yao, W
Chen, J
Chen, Z
Genovese, G
Terao, C
Li, L
Sun, D
author_facet Song, M
Han, Y
Zhao, Y
Lv, J
Yu, C
Pei, P
Yang, L
Millwood, IY
Walters, RG
Chen, Y
Du, H
Yang, X
Yao, W
Chen, J
Chen, Z
Genovese, G
Terao, C
Li, L
Sun, D
author_sort Song, M
collection OXFORD
description Little is known about the prospective association between autosomal mosaic chromosomal alterations (mCAs), a group of large-scale somatic mutations on autosomes, and bladder cancer. Here we utilized data from 99,877 participants who were free of physician-diagnosed cancer at baseline (2004–2008) of the China Kadoorie Biobank to estimate the associations between autosomal mCAs and bladder cancer (ICD-10: C67). A total of 2874 autosomal mCAs events among 2612 carriers (2.6%) were detected. After a median follow-up of 12.4 years, we discovered that participants with all autosomal mCAs exhibited higher risks of bladder cancer, with a multivariable-adjusted hazard ratio (HR) (95% confidence interval [CI]) of 2.60 (1.44, 4.70). The estimate of such association was even stronger for mosaic loss events (HR [95% CI]: 6.68 [2.92, 15.30]), while it was not significant for CN-LOH events. Both expanded (cell fraction ≥10%) and non-expanded autosomal mCAs, as well as mosaic loss, were associated with increased risks of bladder cancer. Of interest, physical activity (PA) significantly modified the associations of autosomal mCAs and mosaic loss (Pinteraction = 0.038 and 0.012, respectively) with bladder cancer. The increased risks of bladder cancer were only observed with mCAs and mosaic loss among participants with a lower level of PA (HR [95% CI]: 5.11 [2.36, 11.09] and 16.30 [6.06, 43.81]), but not among participants with a higher level of PA. Our findings suggest that peripheral leukocyte autosomal mCAs may represent a novel risk factor for bladder cancer, and PA may serve as a potential intervention target for mCAs carriers.
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spelling oxford-uuid:6288494c-ae13-410d-a1e9-3724355a14bf2024-10-01T20:08:01ZAssociation of autosomal mosaic chromosomal alterations with risk of bladder cancer in Chinese adults: a prospective cohort studyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6288494c-ae13-410d-a1e9-3724355a14bfEnglishJisc Publications RouterSpringer Nature [academic journals on nature.com]2024Song, MHan, YZhao, YLv, JYu, CPei, PYang, LMillwood, IYWalters, RGChen, YDu, HYang, XYao, WChen, JChen, ZGenovese, GTerao, CLi, LSun, DLittle is known about the prospective association between autosomal mosaic chromosomal alterations (mCAs), a group of large-scale somatic mutations on autosomes, and bladder cancer. Here we utilized data from 99,877 participants who were free of physician-diagnosed cancer at baseline (2004–2008) of the China Kadoorie Biobank to estimate the associations between autosomal mCAs and bladder cancer (ICD-10: C67). A total of 2874 autosomal mCAs events among 2612 carriers (2.6%) were detected. After a median follow-up of 12.4 years, we discovered that participants with all autosomal mCAs exhibited higher risks of bladder cancer, with a multivariable-adjusted hazard ratio (HR) (95% confidence interval [CI]) of 2.60 (1.44, 4.70). The estimate of such association was even stronger for mosaic loss events (HR [95% CI]: 6.68 [2.92, 15.30]), while it was not significant for CN-LOH events. Both expanded (cell fraction ≥10%) and non-expanded autosomal mCAs, as well as mosaic loss, were associated with increased risks of bladder cancer. Of interest, physical activity (PA) significantly modified the associations of autosomal mCAs and mosaic loss (Pinteraction = 0.038 and 0.012, respectively) with bladder cancer. The increased risks of bladder cancer were only observed with mCAs and mosaic loss among participants with a lower level of PA (HR [95% CI]: 5.11 [2.36, 11.09] and 16.30 [6.06, 43.81]), but not among participants with a higher level of PA. Our findings suggest that peripheral leukocyte autosomal mCAs may represent a novel risk factor for bladder cancer, and PA may serve as a potential intervention target for mCAs carriers.
spellingShingle Song, M
Han, Y
Zhao, Y
Lv, J
Yu, C
Pei, P
Yang, L
Millwood, IY
Walters, RG
Chen, Y
Du, H
Yang, X
Yao, W
Chen, J
Chen, Z
Genovese, G
Terao, C
Li, L
Sun, D
Association of autosomal mosaic chromosomal alterations with risk of bladder cancer in Chinese adults: a prospective cohort study
title Association of autosomal mosaic chromosomal alterations with risk of bladder cancer in Chinese adults: a prospective cohort study
title_full Association of autosomal mosaic chromosomal alterations with risk of bladder cancer in Chinese adults: a prospective cohort study
title_fullStr Association of autosomal mosaic chromosomal alterations with risk of bladder cancer in Chinese adults: a prospective cohort study
title_full_unstemmed Association of autosomal mosaic chromosomal alterations with risk of bladder cancer in Chinese adults: a prospective cohort study
title_short Association of autosomal mosaic chromosomal alterations with risk of bladder cancer in Chinese adults: a prospective cohort study
title_sort association of autosomal mosaic chromosomal alterations with risk of bladder cancer in chinese adults a prospective cohort study
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