Englander Institute for Precision Medicine

Association of clonal hematopoiesis and mosaic chromosomal alterations with solid malignancy incidence and mortality.

TitleAssociation of clonal hematopoiesis and mosaic chromosomal alterations with solid malignancy incidence and mortality.
Publication TypeJournal Article
Year of Publication2024
AuthorsDesai P, Zhou Y, Grenet J, Handelman SK, Crispino CM, Tarbay LN, Whitsel EA, Roboz G, Barac A, Honigberg M, Bick A, Anderson G, Wactawski-Wende J, Swartzlander YAJakubek, Bacon J, Wong J, Ma X, Scheet P, Li Z, Kasi P, Prentice R, Auer P, Manson JAE, Reiner A, Simon M
JournalCancer
Date Published2024 Jul 16
ISSN1097-0142
Abstract

BACKGROUND: Understanding the impact of clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) on solid tumor risk and mortality can shed light on novel cancer pathways.

METHODS: The authors analyzed whole genome sequencing data from the Trans-Omics for Precision Medicine Women's Health Initiative study (n = 10,866). They investigated the presence of CHIP and mCA and their association with the development and mortality of breast, lung, and colorectal cancers.

RESULTS: CHIP was associated with higher risk of breast (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.03-1.64; p = .02) but not colorectal (p = .77) or lung cancer (p = .32). CHIP carriers who developed colorectal cancer also had a greater risk for advanced-stage (p = .01), but this was not seen in breast or lung cancer. CHIP was associated with increased colorectal cancer mortality both with (HR, 3.99; 95% CI, 2.41-6.62; p < .001) and without adjustment (HR, 2.50; 95% CI, 1.32-4.72; p = .004) for advanced-stage and a borderline higher breast cancer mortality (HR, 1.53; 95% CI, 0.98-2.41; p = .06). Conversely, mCA (cell fraction [CF] >3%) did not correlate with cancer risk. With higher CFs (mCA >5%), autosomal mCA was associated with increased breast cancer risk (HR, 1.39; 95% CI, 1.06-1.83; p = .01). There was no association of mCA (>3%) with breast, colorectal, or lung mortality except higher colon cancer mortality (HR, 2.19; 95% CI, 1.11-4.3; p = .02) with mCA >5%.

CONCLUSIONS: CHIP and mCA (CF >5%) were associated with higher breast cancer risk and colorectal cancer mortality individually. These data could inform on novel pathways that impact cancer risk and lead to better risk stratification.

DOI10.1002/cncr.35455
Alternate JournalCancer
PubMed ID39012906
Grant List1 R01 CA248747-01A1 / CA / NCI NIH HHS / United States

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