DNA damage and breast cancer

Davis, Jennifer; Lin, Shiaw-Yih

doi:10.5306/wjco.v2.i9.329

Cited by 73 publications

(53 citation statements)

References 73 publications

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“…By this approach, we were able to identify 46% of the cases showing a prevalence of MGMT methylated signal over unmethylated signal, or the absence of unmethylated signal, a pattern significantly more frequent among BRCA wild-type patients. Impairment of the pathways regulating cell DNA repair, either single strand (nucleotide excision repair, NER, and BER) or double strand (NHEJ and HR), is a common event in breast tumorigenesis [47]. The inverse correlation between MGMT methylation and BRCA mutation may suggest that the simultaneous inactivation in both DNA repair pathways could be redundant in TNBC development.…”

Section: Discussionmentioning

confidence: 99%

Methylation of O 6-methylguanine-DNA methyltransferase (MGMT) promoter gene in triple-negative breast cancer patients

Fumagalli

Pruneri

Possanzini

et al. 2012

Breast Cancer Res Treat

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Triple-negative breast cancers are characterized by the triple-negative (ER/PgR/Her2 negative) phenotype, are frequently associated with BRCA gene mutation, and are not candidate to currently available endocrine and HER2-targeted treatments. MGMT is involved in direct DNA repair exerted by cleavage of mutagenic alkyl adducts within DNA, and its epigenetic silencing confers susceptibility to DNA-damaging alkylating agents in glioblastomas and melanomas. MGMT methylation status has not been extensively investigated in breast cancer patients. The goal of our study was to evaluate the MGMT methylation status in TNBC patients, for most of which BRCA1 and BRCA2 mutational status was known. We evaluated MGMT methylation status by methylation-specific PCR (MSP) in formalin-fixed and paraffin-embedded tumor specimens from 92 TNBC patients. By using the GelDoc system (Biorad) software, the cases were further classified as follows: 0 (absence of methylated signal), 1 (prevalence of unmethylated signal, U/M ratio>1), 2 (prevalence of methylated signal, U/M ratio<1), and 3 (absence of unmethylated signal). MSP products were obtained in 89 (96.7%) of the cases. Overall, 15 (16.9%) cases were classified as 0, 33 (37.1%) cases as 1, 39 (43.8%) cases as 2, and 2 (2.2%) cases as 3. The 48 cases classified as 0 and 1 were considered as MGMT unmethylated, and the 41 cases classified as 2 and 3 as MGMT methylated. The prevalence of MGMT methylation in patients with BRCA1 mutated, wild-type, and unknown was 30.2% (13/43), 63.6% (14/22), and 58.3% (14/24), respectively. MGMT methylation was unrelated to the main clinical pathological characteristics, with the exception of a weak association with advanced age. In conclusion, our data suggest that in TNBC with wild-type BRCA1, the direct DNA repair system may be frequently (63.6%) silenced by MGMT methylation. The evaluation of the MGMT status could offer a new adjunct in predicting tumor response to alkylating drugs in TNBC patients.

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Section: Discussionmentioning

confidence: 99%

Methylation of O 6-methylguanine-DNA methyltransferase (MGMT) promoter gene in triple-negative breast cancer patients

Fumagalli

Pruneri

Possanzini

et al. 2012

Breast Cancer Res Treat

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“…Inherited germline mutations in BRCA1 or BRCA2 genes, the best-known high susceptibility genes of familial breast cancer, increase the life-time risk of the development of breast and ovarian cancer 10 and are responsible for 5-10% of all breast cancers. 11,12 BRCArelated cancers show morphological and immunohistochemical differences, as well as copy number aberrations compared with sporadic breast cancers. These differences may explain the activation of distinct pathways as promoters of carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

Angiogenetic axis angiopoietins/Tie2 and VEGF in familial breast cancer

et al. 2012

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Angiogenesis leads to the formation of blood vessels from pre-existing ones, allowing tumor growth. Vascular endothelial growth factor (VEGF) and Angiopoietins (Ang-1, Ang-2) have a pivotal role in tumor angiogenesis but few data regarding their role in hereditary breast cancer are available. The aim of the present study was to analyze Ang-1, Ang-2, tyrosine-protein kinase receptor Tie2 and VEGF expression and their correlation in a cohort of familial and sporadic breast cancers in order to verify whether the presence of germline mutations in BRCA may have a role in tumor microenvironment regulation. Tumor samples from a cohort of 41 patients with a first diagnosis and a family history of breast cancer and 19 patients with sporadic breast cancers were enrolled. The expression of Tie2, Ang-1, Ang-2 and VEGF were analyzed by quantitative real-time PCR. Patients harboring BRCA mutations had higher levels of Ang-1 (P ¼ 0.05), Ang-2 (P ¼ 0.02) and VEGF (P ¼ 0.04) mRNA compared with those without BRCA mutations (BRCAX). The same was observed in triple-negative breast cancer (TNBC). Moreover, a positive correlation between Ang-2 and VEGF was found in both the familial breast cancer group (BRCA carriers: r ¼ 0.83; Po0.0001 and BRCAX: r ¼ 0.58; P ¼ 0.008) and in TNBC (r ¼ 0.62; P ¼ 0.007). The higher levels of Ang-1, Ang-2 and VEGF mRNA found in BRCA carriers and TNBCs suggest that they could be attractive angiogenic therapeutic targets in these breast cancers.

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“…3 DNA damage from oxidative stress can eventually override tumor suppressors gene repair mechanisms, leading to faulty DNA integration and tumorigenesis. 4 …”

Section: Introductionmentioning

confidence: 99%

Dermal Carotenoid Measurement is Inversely Related to Anxiety in Patients with Breast Cancer

LeCompte

Golod

et al. 2018

Journal of Investigative Medicine

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Breast cancer is the most prevalent malignancy among women worldwide. Increased oxidative stress and poor subjective health outcomes have been associated with increased risk of cancer recurrence and metastasis, but few studies until now have explored the relationship between oxidative stress and chronic stress/anxiety. This study aims to examine the association between anxiety and a potential dermal correlate of oxidative stress in patients with breast cancer. 102 breast cancer patients were enrolled in a cross-sectional study at Highland Hospital, a county hospital in Oakland, California. Each participant’s skin carotenoid score (SCS), a potential dermal correlate of oxidative stress, was recorded via Raman spectroscopy. Patient demographics, breast cancer stage, and subjective health measures (anxiety and self-rated health) were ascertained. Multivariate linear regression analysis was performed to quantify any associations between SCS and the above health correlates. Higher levels of skin carotenoids were associated with decreased severity of anxiety, lower BMI, increased servings of vegetables/fruits in daily diet, Hispanic race, lower educational status, and nonsmoking status. Severity of anxiety as graded by the GAD-7 was inversely associated with dermal carotenoid measurements via SCS. Conclusions. Increased levels of oxidative stress as quantified by SCS is associated with greater severity of anxiety. Because chronic stress has been associated with tumor progression, increased recurrence rates, and increased metastatic risk in breast cancer, non-invasive dermal carotenoid measurements could be used as a novel objective correlate of subjective health during cancer treatment.

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DNA damage and breast cancer

Cited by 73 publications

References 73 publications

Methylation of O 6-methylguanine-DNA methyltransferase (MGMT) promoter gene in triple-negative breast cancer patients

Methylation of O 6-methylguanine-DNA methyltransferase (MGMT) promoter gene in triple-negative breast cancer patients

Angiogenetic axis angiopoietins/Tie2 and VEGF in familial breast cancer

Dermal Carotenoid Measurement is Inversely Related to Anxiety in Patients with Breast Cancer

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