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

Pinkal Desai¹, Ying Zhou², Justin Grenet³, Samuel K Handelman⁴, Cynthia M Crispino¹, Laura N Tarbay¹, Eric A Whitsel^{5

6}, Gail Roboz¹, Ana Barac⁷, Michael Honigberg^{8

9}, Alexander Bick¹⁰, Garnet Anderson¹¹, Jean Wactawski-Wende¹², Yasminka A Jakubek Swartzlander¹³, Jason Bacon¹⁴, Justin Wong¹⁵, Xiaolong Ma¹⁶, Paul Scheet¹⁵, Zichan Li¹⁷, Pashtoon Kasi¹⁸, Ross Prentice¹¹, Paul Auer¹⁹, JoAnn E Manson^{20

21}, Alexander Reiner^{11

22}, Michael Simon²³

Affiliations

¹ Department of Hematology/Oncology, Weill Cornell Medical School, New York, New York, USA.
² Department of Data Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
³ Oregon Health and Science University, Portland, USA.
⁴ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Michigan Medicine at the University of Michigan, Ann Arbor, Michigan, USA.
⁵ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA.
⁶ Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
⁷ CardioOncology Program, Inova Health System, Fairfax, Virginia, USA.
⁸ Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts, USA.
⁹ Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
¹⁰ Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
¹¹ Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington, USA.
¹² Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, New York, USA.
¹³ Department of Internal Medicine, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
¹⁴ Acadix Consulting, Milwaukee, Wisconsin, USA.
¹⁵ Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
¹⁶ Division of Biostatistics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
¹⁷ Computational Biology and Bioinformatics, Englander Institute for Precision Medicine, Weill Cornell Medical School, New York, New York, USA.
¹⁸ Weill Cornell Medicine, Englander Institute of Precision Medicine, New York Presbyterian Hospital, New York, New York, USA.
¹⁹ Department of Biostatistics, Institute for Health and Equity and Cancer Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
²⁰ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
²¹ Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
²² Department of Epidemiology, University of Washington, Seattle, Washington, USA.
²³ Karmanos Cancer Institute, Detroit, Michigan, USA.

PMID: 39012906
DOI: 10.1002/cncr.35455

Free article

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

Pinkal Desai et al. Cancer. 2024.

Free article

. 2024 Nov 15;130(22):3879-3887.

doi: 10.1002/cncr.35455. Epub 2024 Jul 16.

Authors

Affiliations

¹ Department of Hematology/Oncology, Weill Cornell Medical School, New York, New York, USA.
² Department of Data Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
³ Oregon Health and Science University, Portland, USA.
⁴ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Michigan Medicine at the University of Michigan, Ann Arbor, Michigan, USA.
⁵ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA.
⁶ Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
⁷ CardioOncology Program, Inova Health System, Fairfax, Virginia, USA.
⁸ Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts, USA.
⁹ Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
¹⁰ Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
¹¹ Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington, USA.
¹² Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, New York, USA.
¹³ Department of Internal Medicine, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
¹⁴ Acadix Consulting, Milwaukee, Wisconsin, USA.
¹⁵ Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
¹⁶ Division of Biostatistics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
¹⁷ Computational Biology and Bioinformatics, Englander Institute for Precision Medicine, Weill Cornell Medical School, New York, New York, USA.
¹⁸ Weill Cornell Medicine, Englander Institute of Precision Medicine, New York Presbyterian Hospital, New York, New York, USA.
¹⁹ Department of Biostatistics, Institute for Health and Equity and Cancer Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
²⁰ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
²¹ Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
²² Department of Epidemiology, University of Washington, Seattle, Washington, USA.
²³ Karmanos Cancer Institute, Detroit, Michigan, USA.

PMID: 39012906
DOI: 10.1002/cncr.35455

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: breast cancer; clonal hematopoiesis; clonal hematopoiesis of indeterminate potential (CHIP); colorectal cancer; mosaic chromosomal alterations; solid tumor mortality; solid tumors risk.

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References

REFERENCES

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

Affiliations

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

Authors

Affiliations

Abstract

References

REFERENCES

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical