Variability in DNA Repair Capacity Levels among Molecular Breast Cancer Subtypes: Triple Negative Breast Cancer Shows Lowest Repair

Matta, Jaime; Ortíz, Carmen; Encarnación, Jarline; Dutil, Julie; Suárez, Erick

doi:10.3390/ijms18071505

Cited by 13 publications

(10 citation statements)

References 36 publications

(53 reference statements)

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“…The deficiency could be explained by the lower expression of some NER proteins, such as XPA, XPF and CSB [ 11 ]. Among all the subtypes of breast cancer, the TNBC was of the lowest NER capacity [ 12 ]. The excision repair cross complementing-group 1 (ERCC1) gene is located on human chromosome 19q13.32, and encodes a DNA repair protein, ERCC1 [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Contribution of excision repair cross-complementing group 1 genotypes to triple negative breast cancer risk

et al. 2018

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Compared with other subgroups of breast cancer, triple negative breast cancer (TNBC) is considered to be the one with the greatest invasiveness and metastatic mobility, and the highest recurrence rate. Considering the lack of predictive markers for TNBC, we aimed to examine the contribution of excision repair cross complementing-group 1 (ERCC1) genotypes to TNBC. The rs11615 and rs3212986 of ERCC1 were investigated and evaluated for their associations with susceptibility to breast cancer, especially TNBC, in Taiwan. In this study, 1,232 breast cancer patients (104 were TNBC) and 1,232 healthy controls were recruited and their genotypes at ERCC1 rs11615 and rs3212986 were revealed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. Our results indicated that genotypes of ERCC1 rs11615 (Ptrend = 2.2*10E-9), but not rs3212986 (Ptrend = 0.6181), were associated with breast cancer risk. In the allelic frequency distribution analysis, breast cancer patients carried the T allele of ERCC1 rs11615 a higher rate than the control subjects, further supporting the idea that ERCC1 rs11615 TT genotype is positively associated with breast cancer susceptibility. More importantly, the frequency of the ERCC1 rs11615 TT genotype was even higher among TNBC patients than among other subtypes of breast cancer patients (P = 0.0001, odds ratio = 1.73, 95% confidence interval = 1.15–2.63). The genotypes of ERCC1 rs11615 were not associated with Ki67 status. Our findings firstly show that the T allele of ERCC1 rs11615 can serve as a predictive biomarker for breast cancer and TNBC. We believe that ERCC1 could serve as a target for personalized treatment of breast cancer, especially for TNBC.

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Section: Introductionmentioning

confidence: 99%

Contribution of excision repair cross-complementing group 1 genotypes to triple negative breast cancer risk

et al. 2018

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“…To further elucidate the relevance of our results, additional analyses were performed to evaluate whether plasma 25(OH)D levels vary depending on the molecular subtype of the tumor. Since previous studies from our research team showed that the DRC level distribution is positively skewed in BC cases [15], we focused our analysis on BC cases with low DRC levels only. Mean 25(OH)D levels were compared among women with breast tumors that were classified as luminal A, luminal B, HER2+, and TN.…”

Section: Relationship Between Molecular Breast Cancer Subtypes and 25mentioning

confidence: 99%

“…Therefore, it is not surprising that defective DNA repair, measured in lymphocytes, has been identified as a risk factor for different types of cancer [11][12][13], including BC [14]. Variability on DRC levels has been reported among the four principal molecular BC subtypes, where the triple-negative subtype showed the lowest levels [15].…”

Section: Introductionmentioning

confidence: 99%

Circulating Vitamin D Levels and DNA Repair Capacity in Four Molecular Subtypes of Women with Breast Cancer

Ortiz-Sanchéz

Encarnación-Medina

Vergne

et al. 2020

IJMS

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Vitamin D regulates estrogen synthesis among other mechanisms involved in breast cancer (BC) development; however, no evidence has been found regarding its relationship with DNA repair capacity (DRC). Therefore, the objective of this study was to elucidate whether DRC levels are linked with plasma 25(OH)D levels. BC cases and controls were selected from our BC cohort. DRC levels were assessed in lymphocytes through the host-cell reactivation assay. 25(OH)D levels were measured using the UniCel DxI 600 Access Immunoassay System. BC cases (n = 91) showed higher 25(OH)D levels than the controls (n = 92) (p = 0.001). When stratifying BC cases and controls into low and high DRC categories, BC cases with low DRC (n = 74) had the highest 25(OH)D levels (p = 0.0001). A positive correlation between 25(OH)D and DRC levels was found for the controls (r = 0.215, p = 0.043) while a negative correlation was found for BC cases (r = −0.236, p = 0.026). Significant differences in 25(OH)D levels were observed when stratifying by molecular subtypes (p = 0.0025). Our study provides evidence of a link between 25(OH)D and DRC in BC along with a description of to how 25(OH)D levels vary across subtypes. The positive correlation observed in the control group suggests that 25(OH)D contributes differently to DRC levels once the malignancy is developed.

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“…Previous studies from our laboratory demonstrate the critical importance of the overall DRC levels for BC risk through the NER pathway using lymphocytes as surrogate markers [14, 15]. Recently, our laboratory showed that there is substantial variability in overall DRC levels among the four principal molecular BC subtypes and that women with triple-negative (TN) BC have the lowest DRC [16]. These findings confirm the importance of the NER pathway in sporadic BC and highlight the need for more research to understand how changes in DRC levels are associated with multiple endpoints in the complex process of BC carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA Expression Changes in Women with Breast Cancer Stratified by DNA Repair Capacity Levels

Encarnación-Medina

Ortíz

Vergne

et al. 2019

Journal of Oncology

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Breast cancer (BC) is the most commonly diagnosed cancer in women worldwide and is the leading cause of death among Hispanic women. Previous studies have shown that women with a low DNA repair capacity (DRC), measured through the nucleotide excision repair (NER) pathway, have an increased BC risk. Moreover, we previously reported an association between DRC levels and the expression of the microRNA (miRNA) let-7b in BC patients. MiRNAs can induce genomic instability by affecting the cell’s DNA damage response while influencing the cancer pathobiology. The aim of this pilot study is to identify plasma miRNAs related to variations in DRC levels in BC cases. Hypothesis. Our hypothesis consists in testing whether DRC levels can be correlated with miRNA expression levels. Methods. Plasma samples were selected from 56 (27 cases and 29 controls) women recruited as part of our BC cohort. DRC values were measured in lymphocytes using the host-cell reactivation assay. The samples were divided into two categories: low (≤3.8%) and high (>3.8%) DRC levels. MiRNAs were extracted to perform an expression profile analysis. Results. Forty miRNAs were identified to be BC-related (p<0.05, MW), while 18 miRNAs were found to be differentially expressed among BC cases and controls with high and low DRC levels (p<0.05, KW). Among these candidates are miR-299-5p, miR-29b-3p, miR-302c-3p, miR-373-3p, miR-636, miR-331-5p, and miR-597-5p. Correlation analyses revealed that 4 miRNAs were negatively correlated within BC cases with low DRC (p<0.05, Spearman’s correlation). Results from multivariate analyses revealed that the clinicopathological characteristics may not have a direct effect on specific miRNA expression. Conclusion. This pilot study provides evidence of four miRNAs that are negatively regulated in BC cases with low DRC levels. Additional studies are needed in order to have a complete framework regarding the overall DRC levels, miRNA expression profiles, and tumor characteristics.

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Variability in DNA Repair Capacity Levels among Molecular Breast Cancer Subtypes: Triple Negative Breast Cancer Shows Lowest Repair

Cited by 13 publications

References 36 publications

Contribution of excision repair cross-complementing group 1 genotypes to triple negative breast cancer risk

Contribution of excision repair cross-complementing group 1 genotypes to triple negative breast cancer risk

Circulating Vitamin D Levels and DNA Repair Capacity in Four Molecular Subtypes of Women with Breast Cancer

MicroRNA Expression Changes in Women with Breast Cancer Stratified by DNA Repair Capacity Levels

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