scholarly journals DNA Repair Genes as Drug Candidates for Early Breast Cancer Onset in Latin America: A Systematic Review

2021 ◽  
Vol 22 (23) ◽  
pp. 13030
Author(s):  
Laura Keren Urbina-Jara ◽  
Emmanuel Martinez-Ledesma ◽  
Augusto Rojas-Martinez ◽  
Francisco Ricardo Rodriguez-Recio ◽  
Rocio Ortiz-Lopez
Keyword(s):  
Breast Cancer ◽  
Dna Repair ◽  
Cell Lines ◽  
Latin American ◽  
Young Women ◽  
Dna Repair Genes ◽  
Gene Repair ◽  
Drug Candidates ◽  
Large Patient ◽  
Repair Genes

The prevalence of breast cancer in young women (YWBC) has increased alarmingly. Significant efforts are being made to elucidate the biological mechanisms concerning the development, prognosis, and pathological response in early-onset breast cancer (BC) patients. Dysfunctional DNA repair proteins are implied in BC predisposition, progression, and therapy response, underscoring the need for further analyses on DNA repair genes. Public databases of large patient datasets such as METABRIC, TCGA, COSMIC, and cancer cell lines allow the identification of variants in DNA repair genes and possible precision drug candidates. This study aimed at identifying variants and drug candidates that may benefit Latin American (LA) YWBC. We analyzed pathogenic variants in 90 genes involved in DNA repair in public BC datasets from METABRIC, TCGA, COSMIC, CCLE, and COSMIC Cell Lines Project. Results showed that reported DNA repair germline variants in the LA dataset are underrepresented in large databases, in contrast to other populations. Additionally, only six gene repair variants in women under 50 years old from the study population were reported in BC cell lines. Therefore, there is a need for new approaches to study DNA repair variants reported in young women from LA.

Common variants in estrogen metabolism and DNA repair genes associated risk of breast cancer in young women

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 9507-9507
Author(s):  
E. R. Jupe ◽  
D. A. Ralph ◽  
S. Manjeshwar ◽  
D. Lalo ◽  
C. Bromley ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Repair ◽  
Young Women ◽  
Estrogen Metabolism ◽  
Dna Repair Genes ◽  
Common Variants ◽  
Repair Genes

Truncating variants in DNA-repair genes and their effect on AAO of hereditary breast cancer

2018 ◽  
Author(s):  
I Sepahi ◽  
U Faust ◽  
M Sturm ◽  
K Bosse ◽  
M Kehrer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Repair ◽  
Hereditary Breast Cancer ◽  
Dna Repair Genes ◽  
Repair Genes

Polymorphisms in DNA repair genes, ionizing radiation exposure and risk of breast cancer in U.S. Radiologic technologists

2008 ◽  
Vol 122 (1) ◽  
pp. 177-182 ◽  
Author(s):  
Parveen Bhatti ◽  
Jeffery P. Struewing ◽  
Bruce H. Alexander ◽  
Michael Hauptmann ◽  
Laura Bowen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Repair ◽  
Ionizing Radiation ◽  
Radiation Exposure ◽  
Dna Repair Genes ◽  
Radiologic Technologists ◽  
Ionizing Radiation Exposure ◽  
Repair Genes

Clinical outcome prediction in esophageal adenocarcinoma based on tumor and germ-line single nucleotide polymorphisms (SNP) in DNA-repair pathways

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15144-15144 ◽  
Author(s):  
H. Yoon ◽  
K. M. Murphy ◽  
M. K. Gibson
Keyword(s):  
Dna Repair ◽  
Tumor Cells ◽  
Esophageal Adenocarcinoma ◽  
Cell Lines ◽  
Normal Tissue ◽  
Germ Line ◽  
Normal Mucosa ◽  
Snp Analysis ◽  
Dna Repair Genes ◽  
Repair Genes

15144 Background: Germ-line SNPs in DNA repair enzymes are studied as predictive factors in various cancers. More rarely studied, however, is the presence of SNPs in tumor cells and how they relate to both germ-line SNPs as well as outcome. We explored the presence of and relationship between germ-line and tumor SNPs in esophageal adenocarcinoma using two systems: (1) Cell lines, to determine whether loss of heterozygosity (LOH) occurs near DNA repair genes, and for genotyping; (2) Patient samples, to determine whether SNPs differ between normal and tumor mucosa. Methods: (1) For LOH analysis, we examined three short tandem repeat (STR) loci on 19q13.2- 13.3 (near DNA-repair genes XPD, ERCC1, and XRCC1) in four esophageal adenocarcinoma cell lines. (The STR markers have a false positive rate of <10-3 for LOH when all three demonstrate homozygosity.) Then, using a real-time PCR allelic discrimination TaqMan assay (AB), we analyzed two SNPs of interest in these cell lines. (2) We performed SNP analysis on tumor and adjacent normal mucosa from paraffin-embedded esophageal specimens taken at resection in patients with T3N0–1 esophageal adenocarcinoma who received preoperative cisplatin, paclitaxel, gefitinib and radiotherapy followed by transhiatal resection. Results: (1) Cell lines: SEG1 and BiC1 were consistent with LOH, showing a single-allele pattern at XPD 751 (C allele) and XPD 312 (G allele). TE7 and SKGT4 did not have LOH. (2) Tumor and normal tissue: We obtained data on two patients for XPD 751. Genotypes in normal mucosa were heterozygous for one patient and homozygous at the minor allele (Q/Q) for the second patient. Genotypes in tumor were identical to those in normal tissue. Conclusions: Our cell line data shows that LOH occurs in esophageal tumor cells at DNA-repair genes of interest. Our data in two patients with esophageal adenocarcinoma did not demonstrate a difference at XPD 751 between tumor and normal tissue. Given the technical success and encouraging data from this work, we plan to evaluate tissue from ∼90 patients who underwent preoperative cisplatin-based chemoradiotherapy followed by surgery (as part of completed ECOG trial E1201). [Table: see text]

Comparison of germline mutations in African American and Caucasian men with metastatic prostate cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5568-5568
Author(s):  
Elisa Marie Ledet ◽  
Ellen Jaeger ◽  
Whitley Hatton ◽  
Marcus W. Moses ◽  
Alexandra Sokolova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Dna Repair ◽  
African American ◽  
Family History ◽  
Metastatic Prostate Cancer ◽  
Germline Mutations ◽  
Dna Repair Genes ◽  
Brca Mutations ◽  
Repair Genes

5568 Background: The relevance of germline mutations in metastatic prostate cancer is well established; however, comparison of germline genetics in African American (AA) versus Caucasian (CA) men with metastatic prostate cancer (PCa) is limited. Methods: Germline data from self-identified AA and CA metastatic PCa patients (pts) were collected from 5 academic cancer centers. Various commercial cancer-specific germline testing panels were used to evaluate 12-86 genes. Pathogenic (P) or likely pathogenic (LP) mutations, and variants of unknown significance (VUS), were reported according to ACMG guidelines. Self-reported family history (FH) was annotated for 99% of pts. Statistical analyses included Chi-squared and Fischer’s exact tests. Results: A total of 821 metastatic PCa pts were assessed: 152 AAs and 669 CAs. For P/LP alterations, AAs had a frequency of 11.2% (17/152) as compared to a frequency of 14.6% (98/669) in CAs (p = 0.302). AA pts were more likely to have a VUS than CA pts, 61% vs 43% respectively (OR = 2.09, 95%CI [1.45, 2.99], p < 0.001). BRCA mutations were similar between races, but AA were more likely to have a BRCA1 P/LP alteration (OR = 6.00, 95% CI [1.33, 27.09], p = 0.025). AA pts were less likely to have a P/LP alteration in a non-BRCA gene (OR = 0.34, 95% CI [0.15, 0.80], p = 0.013). Among DNA repair genes, there were no significant difference between AA and CA pts (p = 0.574); however, there was a trend toward AA pts having fewer P/LP alteration in a non-BRCA DNA repair genes (OR = 0.26, 95% CI [0.06, 1.08], p = 0.071). In pts with >1 first degree relative (FDR) with ovarian cancer, P/LP germline alterations were more likely in CAs (OR = 2.33, 95% CI [1.05, 5.17], p = 0.043); but there were no significant differences in AAs (p = 0.098). Those with >2 FDRs with PCa were more likely to have a P/LP change in CAs (OR = 2.32, 95% CI [1.04, 5.15], p = 0.043), but there were no difference in AAs (p = 0.700). In pts with ≥2 FDRs with breast cancer, P/LP germline alterations were more likely in both AAs (OR = 9.36, 95% CI [1.72, 50.84], p = 0.019) and CAs (OR = 3.92, 95% CI [1.79, 8.59], p = 0.001). Conclusions: We did not observe a difference in the overall frequency of germline P/LP alterations between AA and CA men with metastatic PCa but VUSs were more common in AA men. These AA men have an overall frequency of BRCA mutations similar to CA men; however, BRCA1 mutations were more prevalent in these AAs. Non-BRCA P/LP mutations are significantly less frequent in AA pts. A positive family history of >2 FDRs with breast cancer was associated with P/LP alterations in both AA and CA pts.

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