Association of Clonal Hematopoiesis and Mosaic Chromosomal Alterations With Solid Malignancy Incidence and Mortality

Authors

Pinkal Desai
Ying Zhou
Justin Grenet
Samuel K Handelman
Cynthia M Crispino
Laura N Tarbay
Eric A Whitsel
Gail Roboz
Ana Barac
Michael Honigberg
Alexander Bick
Garnet Anderson
Jean Wactawski-Wende
Yasminka A Jakubek Swartzlander
Jason Bacon
Justin Wong
Xiaolong Ma
Paul Scheet
Zichan Li
Pashtoon Kasi
Ross Prentice
Paul Auer
JoAnn E Manson
Alexander Reiner
Michael Simon

Language

English

Publication Date

11-15-2024

Journal

Cancer

DOI

10.1002/cncr.35455

PMID

39012906

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.

Keywords

Humans, Female, Clonal Hematopoiesis, Aged, Breast Neoplasms, Middle Aged, Colorectal Neoplasms, Chromosome Aberrations, Incidence, Mosaicism, Lung Neoplasms, Male, Neoplasms, Whole Genome Sequencing, breast cancer, clonal hematopoiesis, clonal hematopoiesis of indeterminate potential (CHIP), colorectal cancer, mosaic chromosomal alterations, solid tumor mortality, solid tumors risk

Published Open-Access

yes

Recommended Citation

Desai, Pinkal; Zhou, Ying; Grenet, Justin; et al., "Association of Clonal Hematopoiesis and Mosaic Chromosomal Alterations With Solid Malignancy Incidence and Mortality" (2024). Faculty, Staff and Student Publications. 6488.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6488