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

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.

Thermal Mechanical Bending Response of Symmetrical Functionally Graded Material Plates.

This paper investigates the thermal mechanical bending response of symmetric functionally graded material (FGM) plates. This article proposes a thermodynamic analysis model of both the FGM plate and FGM sandwich plate, and the model only involves four control equations and four unknown variables. The control equation is based on the refined shear deformation theory and the principle of minimum potential energy. The Navier method is used to solve the control equation. According to the method, numerical examples are provided for the thermo-mechanical bending of the symmetric FGM plate and FGM sandwich plate under a simply supported boundary condition, and the accuracy of the model is verified. Finally, parameter analysis is conducted to investigate the effects of the volume fraction index, side-to-thickness ratio, thermal load, and changes in core thickness on the thermal mechanical bending behavior of the symmetric FGM plate and FGM sandwich plate in detail. It was found that the deflection of the FGM plate is greater than that of the FGM sandwich plate, while the normal stress of the FGM plate is smaller than that of the FGM sandwich plate. Moreover, the FGM plate and FGM sandwich plate are sensitive to nonlinear temperature changes.