Chemotherapy-induced acceleration of DNA methylation-based biological age in breast cancer

Figures & data

Table 1. Study sample characteristics by chemotherapy.

	Before First Cycle	After First Cycle	P
N, n	18	15
Age, mean (SD)	52.7 (10.5)	52.1 (10.9)	0.862
Race, n (%)			0.775
Black	4 (22.2)	4 (26.7)
White	14 (77.8)	11 (73.3)
Δ IEAA, mean (SE)	3.5 (1.6)		0.038
Δ EEAA, mean (SE)	5.3 (2.5)		0.041
Δ PhenoAA, mean (SE)	8.7 (2.3)		0.001
Δ GrimAA, mean (SE)	4.7 (1.1)		<0.001
Δ TLA, mean (SE)	−0.2 (0.1)		0.024
Δ DunedinPACE, mean (SE)	0.2 (0.1)		0.007

All statistics shown are mean and standard deviation/standard error, except for race, which is shown as number of participants and percentage.

Δ represents biological age after the first cycle of chemotherapy minus biological age before the first cycle.

IEAA, intrinsic epigenetic age acceleration; EEAA, extrinsic epigenetic age acceleration; PhenoAA, PhenoAge acceleration; GrimAA, GrimAge acceleration; TLA, telomere length attrition.

Figure 1. Correlation estimates between the GrimAge surrogate biomarkers of blood plasma proteins and chemotherapy.

The column represents chemotherapy and the rows represent the DNA methylation-based biomarkers of GrimAge with the Pearson correlation coefficients reported within each box.

DNAmADM, adrenomedullin; DNAmB2M, beta-2 microglobulin; DNAmCystatinC, cystatin C; DNAmGDF15, growth differentiation factor 15; DNAmLeptin, leptin; DNAmPACKYRS, smoking pack-years; DNAmPAI1, plasminogen activation inhibitor-1; DNAmTIMP1, tissue inhibitor metalloproteinase 1.

Table 2. Multiple linear regression results for the association between markers of biological ageing and chemotherapy.

	B [95% CI]	P
IEAA	3.56 [0.15, 6.97]	0.041
EEAA	5.26 [0.01,10.51]	0.050
PhenoAA	8.63 [3.79, 13.47]	0.001
GrimAA	4.68 [2.27, 7.10]	<0.001
TLA	−0.17 [−0.32, −0.02]	0.027
DunedinPACE	0.15 [0.05, 0.25]	0.006

Results are adjusted for chronological age and race.

Beta coefficients represent the mean change in biological ageing post-chemotherapy treatment compared to pre-chemotherapy treatment.

IEAA, intrinsic epigenetic age acceleration; EEAA, extrinsic epigenetic age acceleration; PhenoAA, PhenoAge acceleration; GrimAA, GrimAge acceleration; TLA, telomere length attrition.

Figure 2. Principal component analysis of the association between markers of biological ageing and chemotherapy.

A. Principal component analysis plot using markers of biological ageing and covariates by chemotherapy status. B. Graphical visualization denoting the direction and contribution for each included variable in the principal component analysis in panel A. Positively and negatively correlated variables demonstrate similar or opposite directionality, respectively. Contribution to chemotherapy discrimination is colour coded from light green (low contribution) to red (high contribution).

IEAA, intrinsic epigenetic age acceleration; EEAA, extrinsic epigenetic age acceleration; PhenoAA, PhenoAge acceleration; GrimAA, GrimAge acceleration; TLA, telomere length attrition

Data availability statement

The dataset used in this analysis is available in NCBI’s Gene Expression Omnibus, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE178887, accession number GSE178887.