Are dietary factors involved in the association of CDH4 methylation and breast cancer risk?

2021 ◽  
pp. 1-36
Author(s):  
Nannan Zhang ◽  
Liangliang Li ◽  
Zhiping Long ◽  
Jinghang Du ◽  
Shuo Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Breast Tissue ◽  
Dietary Habits ◽  
Peripheral Blood Leukocyte ◽  
Dietary Factors ◽  
Interactive Effects ◽  
Breast Cancers ◽  
Newly Diagnosed ◽  
Specific Pcr

Abstract DNA methylation is one of the most important epigenetic modifications in breast cancer (BC) development, and long-term dietary habits have been shown to alter DNA methylation. Cadherin-4 (CDH4, a member of the cadherin family) encodes Ca2+-dependent cell-cell adhesion glycoproteins. We conducted a case-control study (380 newly-diagnosed breast cancers and 439 cancer-free controls) to explore the relationship of CDH4 methylation in peripheral blood leukocyte DNA (PBL), as well as its combined and interactive effects with dietary factors and lifestyle on BC risk. A case-only study (335 newly-diagnosed breast cancers) was conducted to analyze the association between CDH4 methylation in breast tissue DNA and dietary factors. CDH4 methylation were detected using quantitative methylation specific PCR (qMSP). Unconditional logistic regressions were used to analyze the association of CDH4 methylation in PBL DNA and BC risk. Cross-over analysis and unconditional logistic regression were used to calculate the combined and interactive effects between CDH4 methylation in PBL DNA and dietary factors in BC. CDH4 hypermethylation was significantly associated with increased BC risk in PBL DNA (ORadjusted (ORadj)= 2.70, 95% confidence interval (CI)= 1.90-3.83, P<0.001). CDH4 hypermethylation also showed significant combined effects with the consumption of <500 g/week vegetables (ORadj=4.33, 95% CI=2.63-7.10), ≤3 times/week allium vegetables (ORadj=7.00, 95% CI=4.17-11.77), <3 times/week fish (ORadj=7.92, 95% CI=3.79-16.53), <3 times/week milk (ORadj=6.30, 95% CI=3.41-11.66), >3 times/week overnight food (ORadj=4.63, 95% CI=2.69-7.99), ≥250 g/week pork (ORadj=5.59, 95% CI=2.94-10.62), and <1 time/month physical activity (ORadj=4.72, 95% CI=2.87-7.76). Moreover, consuming milk ≥ 1 times/month was significantly related with decreased risk of CDH4 methylation (OR=0.61, 95% CI=0.38-0.99) in breast tissue. Our findings may provide direct guidance on the dietary intake for specific methylated carriers to decrease their risk for developing BC.

scholarly journals The Roles of DNA Demethylases in Triple-Negative Breast Cancer

2021 ◽  
Vol 14 (7) ◽  
pp. 628
Author(s):  
Shoghag Panjarian ◽  
Jean-Pierre J. Issa
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Tumor Suppressor Genes ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Breast Cancers ◽  
Therapeutic Implications ◽  
High Propensity ◽  
Dna Methylation Profile

Triple-negative breast cancers (TNBCs) are very heterogenous, molecularly diverse, and are characterized by a high propensity to relapse or metastasize. Clinically, TNBC remains a diagnosis of exclusion by the lack of hormone receptors (Estrogen Receptor (ER) and Progesterone Receptor (PR)) as well as the absence of overexpression and/or amplification of HER2. DNA methylation plays an important role in breast cancer carcinogenesis and TNBCs have a distinct DNA methylation profile characterized by marked hypomethylation and lower gains of methylations compared to all other subtypes. DNA methylation is regulated by the balance of DNA methylases (DNMTs) and DNA demethylases (TETs). Here, we review the roles of TETs as context-dependent tumor-suppressor genes and/or oncogenes in solid tumors, and we discuss the current understandings of the oncogenic role of TET1 and its therapeutic implications in TNBCs.

scholarly journals Accelerated aging in normal breast tissue of women with breast cancer

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Shoghag Panjarian ◽  
Jozef Madzo ◽  
Kelsey Keith ◽  
Carolyn M. Slater ◽  
Carmen Sapienza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Anomaly Detection ◽  
Breast Tissue ◽  
Preventive Intervention ◽  
Normal Breast Tissue ◽  
Accelerated Aging ◽  
Normal Breast ◽  
Age Related ◽  
Unsupervised Anomaly Detection

Abstract Background DNA methylation alterations have similar patterns in normal aging tissue and in cancer. In this study, we investigated breast tissue-specific age-related DNA methylation alterations and used those methylation sites to identify individuals with outlier phenotypes. Outlier phenotype is identified by unsupervised anomaly detection algorithms and is defined by individuals who have normal tissue age-dependent DNA methylation levels that vary dramatically from the population mean. Methods We generated whole-genome DNA methylation profiles (GSE160233) on purified epithelial cells and used publicly available Infinium HumanMethylation 450K array datasets (TCGA, GSE88883, GSE69914, GSE101961, and GSE74214) for discovery and validation. Results We found that hypermethylation in normal breast tissue is the best predictor of hypermethylation in cancer. Using unsupervised anomaly detection approaches, we found that about 10% of the individuals (39/427) were outliers for DNA methylation from 6 DNA methylation datasets. We also found that there were significantly more outlier samples in normal-adjacent to cancer (24/139, 17.3%) than in normal samples (15/228, 5.2%). Additionally, we found significant differences between the predicted ages based on DNA methylation and the chronological ages among outliers and not-outliers. Additionally, we found that accelerated outliers (older predicted age) were more frequent in normal-adjacent to cancer (14/17, 82%) compared to normal samples from individuals without cancer (3/17, 18%). Furthermore, in matched samples, we found that the epigenome of the outliers in the pre-malignant tissue was as severely altered as in cancer. Conclusions A subset of patients with breast cancer has severely altered epigenomes which are characterized by accelerated aging in their normal-appearing tissue. In the future, these DNA methylation sites should be studied further such as in cell-free DNA to determine their potential use as biomarkers for early detection of malignant transformation and preventive intervention in breast cancer.

scholarly journals Current trends in the treatment of HR+/HER2+ breast cancer

2021 ◽  
Vol 17 (13) ◽  
pp. 1665-1681
Author(s):  
Charlene Kay ◽  
Carlos Martínez-Pérez ◽  
James Meehan ◽  
Mark Gray ◽  
Victoria Webber ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Trastuzumab Emtansine ◽  
Breast Cancers ◽  
Newly Diagnosed ◽  
Luminal A ◽  
New Agents ◽  
Her2 Breast Cancer ◽  
Current Trends

Treatment for HR+/HER2+ patients has been debated, as some tumors within this luminal HER2+ subtype behave like luminal A cancers, whereas others behave like non-luminal HER2+ breast cancers. Recent research and clinical trials have revealed that a combination of hormone and targeted anti-HER2 approaches without chemotherapy provides long-term disease control for at least some HR+/HER2+ patients. Novel anti-HER2 therapies, including neratinib and trastuzumab emtansine, and new agents that are effective in HR+ cancers, including the next generation of oral selective estrogen receptor downregulators/degraders and CDK4/6 inhibitors such as palbociclib, are now being evaluated in combination. This review discusses current trials and results from previous studies that will provide the basis for current recommendations on how to treat newly diagnosed patients with HR+/HER2+ disease.

scholarly journals Age-related DNA methylation in paired normal and tumour breast tissue in Chinese breast cancer patients

Epigenetics ◽  
2020 ◽  
pp. 1-15
Author(s):  
Maeve Kiely ◽  
Lap Ah Tse ◽  
Hela Koka ◽  
Difei Wang ◽  
Priscilla Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Cancer Patients ◽  
Breast Tissue ◽  
Breast Cancer Patients ◽  
Age Related

scholarly journals DNA Methylation and Breast Cancer Risk: An Epigenome-Wide Study of Normal Breast Tissue and Blood

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3088 ◽  
Author(s):  
Kaoutar Ennour-Idrissi ◽  
Dzevka Dragic ◽  
Elissar Issa ◽  
Annick Michaud ◽  
Sue-Ling Chang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Breast Tissue ◽  
Normal Breast Tissue ◽  
Normal Breast ◽  
Breast Epithelium ◽  
Normal Breast Epithelium ◽  
Differentially Methylated Genes

Differential DNA methylation is a potential marker of breast cancer risk. Few studies have investigated DNA methylation changes in normal breast tissue and were largely confounded by cancer field effects. To detect methylation changes in normal breast epithelium that are causally associated with breast cancer occurrence, we used a nested case–control study design based on a prospective cohort of patients diagnosed with a primary invasive hormone receptor-positive breast cancer. Twenty patients diagnosed with a contralateral breast cancer (CBC) were matched (1:1) with 20 patients who did not develop a CBC on relevant risk factors. Differentially methylated Cytosine-phosphate-Guanines (CpGs) and regions in normal breast epithelium were identified using an epigenome-wide DNA methylation assay and robust linear regressions. Analyses were replicated in two independent sets of normal breast tissue and blood. We identified 7315 CpGs (FDR < 0.05), 52 passing strict Bonferroni correction (p < 1.22 × 10−7) and 43 mapping to known genes involved in metabolic diseases with significant enrichment (p < 0.01) of pathways involving fatty acids metabolic processes. Four differentially methylated genes were detected in both site-specific and regions analyses (LHX2, TFAP2B, JAKMIP1, SEPT9), and three genes overlapped all three datasets (POM121L2, KCNQ1, CLEC4C). Once validated, the seven differentially methylated genes distinguishing women who developed and who did not develop a sporadic breast cancer could be used to enhance breast cancer risk-stratification, and allow implementation of targeted screening and preventive strategies that would ultimately improve breast cancer prognosis.

Breast Cancer

2017 ◽  
Author(s):  
Louise A. Brinton ◽  
Mia M. Gaudet ◽  
Gretchen L. Gierach
Keyword(s):  
Breast Cancer ◽  
United States ◽  
Risk Factors ◽  
Cellular Proliferation ◽  
Breast Cancer Incidence ◽  
Ovarian Hormones ◽  
The United States ◽  
Cumulative Exposure ◽  
Breast Cancers ◽  
Newly Diagnosed

Breast cancer is the most frequently diagnosed cancer in women worldwide, with annual estimates of 1.7 million newly diagnosed cases and 522,000 deaths. Although more breast cancers are diagnosed in economically developed than in developing countries, the reverse is true for mortality, reflecting limited screening and less effective treatments in the latter. Breast cancer incidence has been on the rise in the United States for many years, but in recent years this is restricted to certain subgroups, while internationally there have been continued generalized increases, likely reflecting adoption of more Westernized lifestyles. Breast cancer is widely recognized as being hormonally influenced, with most of the established risk factors believed to reflect the influence of cumulative exposure of the breast to stimulatory effects of ovarian hormones—leading to increased cellular proliferation, which in turn can result in genetic errors during cell division.

scholarly journals Exposures in early life: associations with DNA promoter methylation in breast tumors

2012 ◽  
Vol 4 (2) ◽  
pp. 182-190 ◽  
Author(s):  
M.-H. Tao ◽  
C. Marian ◽  
P. G. Shields ◽  
N. Potischman ◽  
J. Nie ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Birth Order ◽  
Promoter Methylation ◽  
Early Life ◽  
Breast Tumors ◽  
Age At Menarche ◽  
Breast Cancers ◽  
Early Life Exposures ◽  
E Cadherin

There is evidence that epigenetic changes occur early in breast carcinogenesis. We hypothesized that early-life exposures associated with breast cancer would be associated with epigenetic alterations in breast tumors. In particular, we examined DNA methylation patterns in breast tumors in association with several early-life exposures in a population-based case–control study. Promoter methylation of E-cadherin, p16 and RAR-β2 genes was assessed in archived tumor blocks from 803 cases with real-time methylation-specific PCR. Unconditional logistic regression was used for case–case comparisons of those with and without promoter methylation. We found no differences in the prevalence of DNA methylation of the individual genes by age at menarche, age at first live birth and weight at age 20. In case–case comparisons of premenopausal breast cancer, lower birth weight was associated with increased likelihood of E-cadherin promoter methylation (OR = 2.79, 95% CI, 1.15–6.82, for ⩽2.5 v. 2.6–2.9 kg); higher adult height with RAR-β2 methylation (OR = 3.34, 95% CI, 1.19–9.39, for ⩾1.65 v. <1.60 m); and not having been breastfed with p16 methylation (OR = 2.75, 95% CI, 1.14–6.62). Among postmenopausal breast cancers, birth order was associated with increased likelihood of p16 promoter methylation. Being other than first in the birth order was inversely associated with likelihood of ⩾1 of the three genes being methylated for premenopausal breast cancers, but positively associated with methylation in postmenopausal women. These results suggest that there may be alterations in methylation associated with early-life exposures that persist into adulthood and affect breast cancer risk.

scholarly journals The Other Side of the Coin: May Androgens Have a Role in Breast Cancer Risk?

2021 ◽  
Vol 23 (1) ◽  
pp. 424
Author(s):  
Chiara Chiodo ◽  
Catia Morelli ◽  
Fabiola Cavaliere ◽  
Diego Sisci ◽  
Marilena Lanzino
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Breast Tissue ◽  
Estrogen Receptor Α ◽  
Epidemiological Studies ◽  
Breast Cancers ◽  
Cancer Risk Factors ◽  
Increased Risk ◽  
The Impact

Breast cancer prevention is a major challenge worldwide. During the last few years, efforts have been made to identify molecular breast tissue factors that could be linked to an increased risk of developing the disease in healthy women. In this concern, steroid hormones and their receptors are key players since they are deeply involved in the growth, development and lifetime changes of the mammary gland and play a crucial role in breast cancer development and progression. In particular, androgens, by binding their own receptor, seem to exert a dichotomous effect, as they reduce cell proliferation in estrogen receptor α positive (ERα+) breast cancers while promoting tumour growth in the ERα negative ones. Despite this intricate role in cancer, very little is known about the impact of androgen receptor (AR)-mediated signalling on normal breast tissue and its correlation to breast cancer risk factors. Through an accurate collection of experimental and epidemiological studies, this review aims to elucidate whether androgens might influence the susceptibility for breast cancer. Moreover, the possibility to exploit the AR as a useful marker to predict the disease will be also evaluated.

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