Blood Epigenetic Age may Predict Cancer Incidence and Mortality

Zheng, Yinan; Joyce, Brian T.; Colicino, Elena; Liu, Lei; Zhang, Wei; Dai, Qi; Shrubsole, Martha J.; Kibbe, Warren A.; Gao, Tao; Zhang, Zhou; Jafari, Nadereh; Vokonas, Pantel; Schwartz, Joel; Baccarelli, Andrea A.; Hou, Lifang

doi:10.1016/j.ebiom.2016.02.008

Cited by 176 publications

(176 citation statements)

References 27 publications

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“…Our findings were consistent with the previous studies in different tissues [4,16]. The epigenetic clock derived from the DNAm age is robust with respect to the batch effects and can be applied to all Illumina array platforms: the EPIC chip (850K), the Illumina 450K array and the 27K array [4] and possibly measures a cell intrinsic and tissue independent epigenetic drift [46]. For blood derived DNA measured on the Illumina 450K array, the epigenetic clock algorithm provides not only several measures of age acceleration but also estimates of blood cell counts.…”

Section: Discussionsupporting

confidence: 90%

DNA methylome analysis identifies accelerated epigenetic ageing associated with postmenopausal breast cancer susceptibility

Ambatipudi

Horvath

Perrier

et al. 2017

European Journal of Cancer

158

152

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Aim of the study A vast majority of human malignancies are associated with ageing, and age is a strong predictor of cancer risk. Recently, DNA methylation-based marker of ageing, known as ‘epigenetic clock’, has been linked with cancer risk factors. This study aimed to evaluate whether the epigenetic clock is associated with breast cancer risk susceptibility and to identify potential epigenetics-based biomarkers for risk stratification. Methods Here, we profiled DNA methylation changes in a nested case–control study embedded in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (n = 960) using the Illumina HumanMethylation 450K BeadChip arrays and used the Horvath age estimation method to calculate epigenetic age for these samples. Intrinsic epigenetic age acceleration (IEAA) was estimated as the residuals by regressing epigenetic age on chronological age. Results We observed an association between IEAA and breast cancer risk (OR, 1.04; 95% CI, 1.007–1.076, P = 0.016). One unit increase in IEAA was associated with a 4% increased odds of developing breast cancer (OR, 1.04; 95% CI, 1.007–1.076). Stratified analysis based on menopausal status revealed that IEAA was associated with development of postmenopausal breast cancers (OR, 1.07; 95% CI, 1.020–1.11, P = 0.003). In addition, methylome-wide analyses revealed that a higher mean DNA methylation at cytosine-phosphate-guanine (CpG) islands was associated with increased risk of breast cancer development (OR per 1 SD = 1.20; 95 %CI: 1.03–1.40, P = 0.02) whereas mean methylation levels at non-island CpGs were indistinguishable between cancer cases and controls. Conclusion Epigenetic age acceleration and CpG island methylation have a weak, but statistically significant, association with breast cancer susceptibility.

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Section: Discussionsupporting

confidence: 90%

DNA methylome analysis identifies accelerated epigenetic ageing associated with postmenopausal breast cancer susceptibility

Ambatipudi

Horvath

Perrier

et al. 2017

European Journal of Cancer

158

152

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“…On the contrary, age acceleration computed with Horvath's epigenetic clock, together with FHL2 clock, were associated with CRC development in males [42, 43]. …”

Section: Resultsmentioning

confidence: 99%

Acceleration of leukocytes’ epigenetic age as an early tumor and sex-specific marker of breast and colorectal cancer

et al. 2017

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Changes in blood epigenetic age have been associated with several pathological conditions and have recently been described to anticipate cancer development. In this work, we analyze a publicly available leukocytes methylation dataset to evaluate the relation between DNA methylation age and the prospective development of specific types of cancer. We calculated DNA methylation age acceleration using five state-of-the-art estimators (three multi-site: Horvath, Hannum, Weidner; and two CpG specific: ELOV2 and FHL2) in a cohort including 845 subjects from the EPIC-Italy project and we compared 424 samples that remained cancer-free over the approximately ten years of follow-up with 235 and 166 subjects who developed breast and colorectal cancer, respectively. We show that the epigenetic age estimated from blood DNA methylation data is statistically significantly associated to future breast and male colorectal cancer development. These results are corroborated by survival analysis that shows significant association between age acceleration and cancer incidence suggesting that the chance of developing age-related diseases may be predicted by circulating epigenetic markers, with a dependence upon tumor type, sex and age estimator. These are encouraging results towards the non-invasive and perspective usage of epigenetic biomarkers.

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“…In a study based on 43 cases, the risk of lung cancer was increased by an estimated 50% per five‐year age acceleration . Another small study (132 cancer cases) concluded that age acceleration was associated with increased cancer risk and shorter cancer survival . A recent study of 480 breast cancer cases and matched controls reported a 4% increase breast cancer risk per one‐year age acceleration.…”

mentioning

confidence: 99%

DNA methylation‐based biological aging and cancer risk and survival: Pooled analysis of seven prospective studies

Dugué

Bassett

Joo

et al. 2017

Intl Journal of Cancer

170

166

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The association between aging and cancer is complex. Recent studies have developed measures of biological aging based on DNA methylation and called them "age acceleration." We aimed to assess the associations of age acceleration with risk of and survival from seven common cancers. Seven case-control studies of DNA methylation and colorectal, gastric, kidney, lung, prostate and urothelial cancer and B-cell lymphoma nested in the Melbourne Collaborative Cohort Study were conducted. Cancer cases, vital status and cause of death were ascertained through linkage with cancer and death registries. Conditional logistic regression and Cox models were used to estimate odds ratios (OR) and hazard ratios (HR) and 95% confidence intervals (CI) for associations of five age acceleration measures derived from the Human Methylation 450 K Beadchip assay with cancer risk (N = 3,216 cases) and survival (N = 1,726 deaths), respectively. Epigenetic aging was associated with increased cancer risk, ranging from 4% to 9% per five-year age acceleration for the 5 measures considered. Heterogeneity by study was observed, with stronger associations for risk of kidney cancer and B-cell lymphoma. An associated increased risk of death following cancer diagnosis ranged from 2% to 6% per five-year age acceleration, with no evidence of heterogeneity by cancer site. Cancer risk and mortality were increased by 15-30% for the fourth versus first quartile of age acceleration. DNA methylation-based measures of biological aging are associated with increased cancer risk and shorter cancer survival, independently of major health risk factors.

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Blood Epigenetic Age may Predict Cancer Incidence and Mortality

Cited by 176 publications

References 27 publications

DNA methylome analysis identifies accelerated epigenetic ageing associated with postmenopausal breast cancer susceptibility

DNA methylome analysis identifies accelerated epigenetic ageing associated with postmenopausal breast cancer susceptibility

Acceleration of leukocytes’ epigenetic age as an early tumor and sex-specific marker of breast and colorectal cancer

DNA methylation‐based biological aging and cancer risk and survival: Pooled analysis of seven prospective studies

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