Department of Hematology/Oncology, Weill Cornell Medical School, New York, New York, USA.
Department of Data Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Cancer. 2024 Nov 15;130(22):3879-3887. doi: 10.1002/cncr.35455. Epub 2024 Jul 16.
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.
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.
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%.
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.
了解不确定潜能的克隆性造血（CHIP）和镶嵌性染色体改变（mCA）对实体瘤风险和死亡率的影响，可以揭示新的癌症途径。
作者分析了来自 Trans-Omics for Precision Medicine Women's Health Initiative 研究（n=10866）的全基因组测序数据。他们研究了 CHIP 和 mCA 的存在及其与乳腺癌、肺癌和结直肠癌的发生和死亡率的关系。
CHIP 与乳腺癌（危险比 [HR]，1.30；95%置信区间 [CI]，1.03-1.64；p=0.02）的风险升高相关，但与结直肠癌（p=0.77）或肺癌（p=0.32）无关。发生结直肠癌的 CHIP 携带者也有更高的晚期风险（p=0.01），但在乳腺癌或肺癌中并未见到。CHIP 与结直肠癌死亡率的增加相关，无论是在调整（HR，3.99；95%CI，2.41-6.62；p<0.001）还是不调整（HR，2.50；95%CI，1.32-4.72；p=0.004）晚期和乳腺癌死亡率有一个边缘升高（HR，1.53；95%CI，0.98-2.41；p=0.06）。相反，mCA（细胞分数 [CF]>3%）与癌症风险无关。随着 CF 升高（mCA>5%），常染色体 mCA 与乳腺癌风险增加相关（HR，1.39；95%CI，1.06-1.83；p=0.01）。mCA（>3%）与乳腺癌、结直肠癌或肺癌死亡率之间没有关联，除了 mCA>5%时结肠癌死亡率更高（HR，2.19；95%CI，1.11-4.3；p=0.02）。
CHIP 和 mCA（CF>5%）分别与乳腺癌风险增加和结直肠癌死亡率增加相关。这些数据可以为影响癌症风险的新途径提供信息，并导致更好的风险分层。
