scholarly journals Differential DNA methylation analysis of breast cancer reveals the impact of immune signaling in radiation therapy

2014 ◽  
Vol 135 (9) ◽  
pp. 2085-2095 ◽  
Author(s):  
Ann Rita Halvorsen ◽  
Åslaug Helland ◽  
Thomas Fleischer ◽  
Karen Marie Haug ◽  
Grethe Irene Grenaker Alnæs ◽  
...  
2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Fereshteh Shahrabi Farahani ◽  
Keiu Paapsi ◽  
Kaire Innos

Abstract Background Radiation therapy is an important part of multimodal breast cancer treatment. The aim was to examine the impact of sociodemographic factors on radiation therapy use in breast cancer (BC) patients in Estonia, linking cancer registry data to administrative databases. Methods Estonian Cancer Registry provided data on women diagnosed with BC in Estonia in 2007–2018, including TNM stage at diagnosis. Use of radiation therapy within 12 months of diagnosis was determined from Estonian Health Insurance Funds claims, and sociodemographic characteristics from population registry. Receipt of radiation therapy was evaluated over time and by clinical and sociodemographic factors. Poisson regression with robust variance was used to calculate univariate and multivariate prevalence rate ratios (PRR) with 95 % confidence intervals (CI) for receipt of radiation therapy among stage I–III BC patients age < 70 years who underwent primary surgery. Results Overall, of 8637 women included in the study, 4310 (50 %) received radiation therapy within 12 months of diagnosis. This proportion increased from 39 to 58 % from 2007 to 2009 to 2016–2018 (p < 0.001). Multivariate regression analysis showed that compared to women with stage I BC, those with more advanced stage were less likely to receive radiation therapy. Receipt of radiation therapy increased significantly over time and was nearly 40 % higher in 2016–2018 than in 2007–2009. Use of radiation therapy was significantly lower for women with the lowest level of education compared to those with a university degree (PRR 0.88, 95 % CI 0.80–0.97), and for divorced/widowed women (PRR 0.95, 95 % CI 0.91–0.99) and single women (PRR 0.92, 95 % CI 0.86–0.99), compared to married women. Age at diagnosis, nationality and place of residence were not associated with receipt of radiation therapy. Conclusions The study showed considerable increase in the use of radiation therapy in Estonia over the study period, which is in line with increases in available equipment. The lack of geographic variations suggests equal access to therapy for patients living in remote regions. However, educational level and marital status were significantly associated with receipt of radiation therapy, highlighting the importance of psychosocial support in ensuring equal access to care.


2021 ◽  
Vol 16 (3) ◽  
pp. S490
Author(s):  
D.M. Aguilar-Beltrán ◽  
A.G. Alcázar-Ramos ◽  
A.L. Vega-Rodríguez ◽  
D.G. García-Gutiérrez ◽  
A.D. Bertadillo-Jilote ◽  
...  

Breast Care ◽  
2020 ◽  
pp. 1-9
Author(s):  
Rudolf Napieralski ◽  
Gabriele Schricker ◽  
Gert Auer ◽  
Michaela Aubele ◽  
Jonathan Perkins ◽  
...  

<b><i>Background:</i></b> PITX2 DNA methylation has been shown to predict outcomes in high-risk breast cancer patients after anthracycline-based chemotherapy. To determine its prognostic versus predictive value, the impact of PITX2 DNA methylation on outcomes was studied in an untreated cohort vs. an anthracycline-treated triple-negative breast cancer (TNBC) cohort. <b><i>Material and Methods:</i></b> The percent DNA methylation ratio (PMR) of paired-like homeodomain transcription factor 2 (PITX2) was determined by a validated methylation-specific real-time PCR test. Patient samples of routinely collected archived formalin-fixed paraffin-embedded (FFPE) tissue and clinical data from 144 TNBC patients of 2 independent cohorts (i.e., 66 untreated patients and 78 patients treated with anthracycline-based chemotherapy) were analyzed. <b><i>Results:</i></b> The risk of 5- and 10-year overall survival (OS) increased continuously with rising PITX2 DNA methylation in the anthracycline-treated population, but it increased only slightly during 10-year follow-up time in the untreated patient population. PITX2 DNA methylation with a PMR cutoff of 2 did not show significance for poor vs. good outcomes (OS) in the untreated patient cohort (HR = 1.55; <i>p</i> = 0.259). In contrast, the PITX2 PMR cutoff of 2 identified patients with poor (PMR &#x3e;2) vs. good (PMR ≤2) outcomes (OS) with statistical significance in the anthracycline-treated cohort (HR = 3.96; <i>p</i> = 0.011). The results in the subgroup of patients who did receive anthracyclines only (no taxanes) confirmed this finding (HR = 5.71; <i>p</i> = 0.014). <b><i>Conclusion:</i></b> In this hypothesis-generating study PITX2 DNA methylation demonstrated predominantly predictive value in anthracycline treatment in TNBC patients. The risk of poor outcome (OS) correlates with increasing PITX2 DNA methylation.


2021 ◽  
Vol 22 (8) ◽  
pp. 4247
Author(s):  
Andrea Martisova ◽  
Jitka Holcakova ◽  
Nasim Izadi ◽  
Ravery Sebuyoya ◽  
Roman Hrstka ◽  
...  

DNA methylation, i.e., addition of methyl group to 5′-carbon of cytosine residues in CpG dinucleotides, is an important epigenetic modification regulating gene expression, and thus implied in many cellular processes. Deregulation of DNA methylation is strongly associated with onset of various diseases, including cancer. Here, we review how DNA methylation affects carcinogenesis process and give examples of solid tumors where aberrant DNA methylation is often present. We explain principles of methods developed for DNA methylation analysis at both single gene and whole genome level, based on (i) sodium bisulfite conversion, (ii) methylation-sensitive restriction enzymes, and (iii) interactions of 5-methylcytosine (5mC) with methyl-binding proteins or antibodies against 5mC. In addition to standard methods, we describe recent advances in next generation sequencing technologies applied to DNA methylation analysis, as well as in development of biosensors that represent their cheaper and faster alternatives. Most importantly, we highlight not only advantages, but also disadvantages and challenges of each method.


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