Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are each associated with an increased risk of developing breast cancer and dying from colorectal cancer, according to research published in Cancer. The study highlights the potential of CHIP and mCAs as biomarkers for cancer risk and mortality, warranting further investigation into their underlying mechanisms and therapeutic implications.
Study Details
The researchers analyzed whole-genome sequencing data from 11,029 women in the Trans-Omics for Precision Medicine cohort of the Women’s Health Initiative study. After exclusions, the cohort included 8561 patients who did not have cancer and 1815 patients who did. In the cancer cohort, 614 patients had breast cancer, 342 had lung cancer, and 307 had colorectal cancer.
CHIP was found in 8.7% of patients with cancer and 8.2% of those without cancer. mCAs were identified in 17.6% of patients with cancer and 19.1% of those without cancer. Both CHIP and mCAs were found in 0.63% of patients.
CHIP and Cancer Risk
The presence of CHIP was associated with an increased risk of developing breast cancer (hazard ratio [HR], 1.30; 95% CI, 1.03-1.64; P =.02), but there was no association between CHIP and the risk of lung cancer (HR, 1.17; 95% CI, 0.86-1.60; P =.32) or colorectal cancer (HR, 1.05; 95% CI, 0.74-1.50; P =.77).
CHIP was associated with an increased risk of death from colorectal cancer both when the researchers adjusted for disease stage at diagnosis (HR, 2.50; 95% CI, 1.32-4.72; P = .004) and when they did not (HR, 3.99; 95% CI, 2.41-6.62; P <.001).
CHIP was not significantly associated with an increased risk of death from breast or lung cancer, regardless of adjustment for disease stage.
mCAs and Cancer Risk
The researchers did not find any associations between cancer risk or death and mCAs with a cell fraction greater than 3%. However, with a cell fraction greater than 5%, autosomal mCAs were associated with an increased risk of developing breast cancer (HR, 1.39; 95% CI, 1.06-1.83; P =.01) and dying from colon cancer (HR, 2.19; 95% CI, 1.11-4.3; P =.02).
Implications and Future Directions
“Understanding the biology behind the association of increased cancerâspecific mortality with CHIP and mCA would not only help stratify risk in these patients but may also help elucidate novel biological pathways that are active in these cancers with CHIP and/or mCA that could have therapeutic implications,” the researchers concluded.
