DNA methylation age in paired tumor and adjacent normal breast tissue in Chinese women with breast cancer.

BACKGROUND: Few studies have examined epigenetic age acceleration (AA), the difference between DNA methylation (DNAm) predicted age and chronological age, in relation to somatic genomic features in paired cancer and normal tissue, with less work done in non-European populations. In this study, we aimed to examine DNAm age and its associations with breast cancer risk factors, subtypes, somatic genomic profiles including mutation and copy number alterations and other aging markers in breast tissue of Chinese breast cancer (BC) patients from Hong Kong. METHODS: We performed genome-wide DNA methylation profiling of 196 tumor and 188 paired adjacent normal tissue collected from Chinese BC patients in Hong Kong (HKBC) using Illumina MethylationEPIC array. The DNAm age was calculated using Horvath's pan-tissue clock model. Somatic genomic features were based on data from RNA sequencing (RNASeq), whole-exome sequencing (WES), and whole-genome sequencing (WGS). Pearson's correlation (r), Kruskal-Wallis test, and regression models were used to estimate associations of DNAm AA with somatic features and breast cancer risk factors. RESULTS: DNAm age showed a stronger correlation with chronological age in normal (Pearson r = 0.78, P < 2.2e-16) than in tumor tissue (Pearson r = 0.31, P = 7.8e-06). Although overall DNAm age or AA did not vary significantly by tissue within the same individual, luminal A tumors exhibited increased DNAm AA (P = 0.004) while HER2-enriched/basal-like tumors exhibited markedly lower DNAm AA (P = < .0001) compared with paired normal tissue. Consistent with the subtype association, tumor DNAm AA was positively correlated with ESR1 (Pearson r = 0.39, P = 6.3e-06) and PGR (Pearson r = 0.36, P = 2.4e-05) gene expression. In line with this, we found that increasing DNAm AA was associated with higher body mass index (P = 0.039) and earlier age at menarche (P = 0.035), factors that are related to cumulative exposure to estrogen. In contrast, variables indicating extensive genomic instability, such as TP53 somatic mutations, high tumor mutation/copy number alteration burden, and homologous repair deficiency were associated with lower DNAm AA. CONCLUSIONS: Our findings provide additional insights into the complexity of breast tissue aging that is associated with the interaction of hormonal, genomic, and epigenetic mechanisms in an East Asian population.

Associations between Preserved Foods and Breast Cancer Risk in Hong Kong Chinese Women.

Preserved food such as cured foods may contain nitrate and nitrite that may contribute to the breast cancer development. Evidence on the associations between these preserved food intakes and risk of breast cancer is sparse. This study aimed to examine the associations between preserved foods (i.e., cured meat, pickled vegetables, canned meat, and canned fruit/vegetables) and breast cancer risk in Hong Kong Chinese women. A total of 1,307 breast cancer cases and 1,050 age-matched controls were recruited from three hospitals during November 2011 through January 2018. We used a standardized questionnaire to collect information on dietary factors, including preserved foods. Unconditional multiple logistic regression was performed to calculate the adjusted odds ratio (AOR) of breast cancer in relation to preserved food with adjustment of potential confounders. We further performed stratified analysis according to the breast cancer biology subtypes. We found that cured meat consumption was significantly associated with the risk of breast cancer [AOR, 1.32; 95% confidence interval 95% (CI), 1.06-1.64]. Compared with no cured meat consumption, cured meat intake ≥ once per week was associated with an AOR of 2.66 (95% CI, 1.38-5.35). Women with canned fruit/vegetable ≥ consumption once per week had a higher risk of breast cancer (OR, 1.19; 95% CI, 1.00-1.41), particularly for the HER2-positive subtypes, but it became borderline after adjustment of confounders. Our study reveals a positive association between consumption of cured meat and breast cancer risk in Chinese population. Cured meat intake might be a potential novel risk factor for breast cancer but this would have to be confirmed by large prospective cohort studies. PREVENTION RELEVANCE: The main finding of this case-control study, an association between cured meat intake and a higher risk of breast cancer in Hong Kong Chinese women, contributes to the growing evidence for population-level health benefits of reducing cured meat consumption.