scholarly journals Functional Polymorphisms in DNA Repair Genes Are Associated with Sporadic Colorectal Cancer Susceptibility and Clinical Outcome

2018 ◽  
Vol 20 (1) ◽  
pp. 97 ◽  
Author(s):  
Katerina Jiraskova ◽  
David Hughes ◽  
Stefanie Brezina ◽  
Tanja Gumpenberger ◽  
Veronika Veskrnova ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Repair ◽  
Clinical Outcome ◽  
Candidate Gene Approach ◽  
Sporadic Colorectal Cancer ◽  
Dna Repair Genes ◽  
Single Nucleotide ◽  
Functional Polymorphisms ◽  
Repair Pathways ◽  
Repair Genes

DNA repair processes are involved in both the onset and treatment efficacy of colorectal cancer (CRC). A change of a single nucleotide causing an amino acid substitution in the corresponding protein may alter the efficiency of DNA repair, thus modifying the CRC susceptibility and clinical outcome. We performed a candidate gene approach in order to analyze the association of non-synonymous single nucleotide polymorphisms (nsSNPs) in the genes covering the main DNA repair pathways with CRC risk and clinical outcome modifications. Our candidate polymorphisms were selected according to the foremost genomic and functional prediction databases. Sixteen nsSNPs in 12 DNA repair genes were evaluated in cohorts from the Czech Republic and Austria. Apart from the tumor-node-metastasis (TNM) stage, which occurred as the main prognostic factor in all of the performed analyses, we observed several significant associations of different nsSNPs with survival and clinical outcomes in both cohorts. However, only some of the genes (REV3L, POLQ, and NEIL3) were prominently defined as prediction factors in the classification and regression tree analysis; therefore, the study suggests their association for patient survival. In summary, we provide observational and bioinformatics evidence that even subtle alterations in specific proteins of the DNA repair pathways may contribute to CRC susceptibility and clinical outcome.

POLYMORPHISMS OF BIOTRANSFORMATION AND DNA REPAIR GENES, DIETARY AND RISK OF COLORECTAL CANCER IN TAIWAN

Epidemiology ◽  
2004 ◽  
Vol 15 (4) ◽  
pp. S150
Author(s):  
Chih-Ching Yeh ◽  
Fung-Chang Sung ◽  
Reiping Tang ◽  
Chung Rong Chang-Chieh ◽  
Ling-Ling Hsieh
Keyword(s):  
Colorectal Cancer ◽  
Dna Repair ◽  
Dna Repair Genes ◽  
Repair Genes

scholarly journals Genetic Variants of DNA Repair Genes as Predictors of Radiation-Induced Subcutaneous Fibrosis in Oropharyngeal Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Ankita Gupta ◽  
Don Mathew ◽  
Shabir Ahmad Bhat ◽  
Sushmita Ghoshal ◽  
Arnab Pal
Keyword(s):  
Dna Repair ◽  
Genetic Variants ◽  
Oropharyngeal Carcinoma ◽  
Dna Repair Genes ◽  
Nucleotide Polymorphisms ◽  
Radical Radiotherapy ◽  
Single Nucleotide ◽  
Radiation Induced ◽  
Repair Genes ◽  
Severe Fibrosis

PurposeTo investigate the impact of genetic variants of DNA repair and pro-fibrotic pathway genes on the severity of radiation-induced subcutaneous fibrosis in patients of oropharyngeal carcinoma treated with radical radiotherapy.Materials and MethodsPatients of newly diagnosed squamous cell carcinoma of oropharynx being treated with two-dimensional radical radiotherapy were enrolled in the study. Patients who had undergone surgery or were receiving concurrent chemotherapy were excluded. Patients were followed up at 6 weeks post completion of radiotherapy and every 3 months thereafter for a median of 16 months. Subcutaneous fibrosis was graded according to the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) grading system and the maximum grade was recorded over the length of the patient’s follow-up. Patients with severe fibrosis (≥G3), were compared to patients with minor (≤G2) fibrotic reactions. Eight single nucleotide polymorphisms of 7 DNA repair genes and 2 polymorphisms of a single pro-fibrotic pathway gene were analyzed by Polymerase Chain Reaction and Restriction Fragment Length Polymorphism and were correlated with the severity of subcutaneous fibrosis.Results179 patients were included in the analysis. Subcutaneous fibrosis was seen in 168 (93.9%) patients. 36 (20.1%) patients had severe (grade 3) fibrosis. On multivariate logistic regression analysis, Homozygous CC genotype of XRCC3 (722C>T, rs861539) (p=0.013*, OR 2.350, 95% CI 1.089-5.382), Homozygous AA genotype of ERCC4 Ex8 (1244G>A, rs1800067) (p=0.001**, OR 11.626, 95% CI 2.490-275.901) and Homozygous TT genotype of XRCC5 (1401G>T, rs828907) (p=0.020*, OR 2.188, 95% CI 1.652-7.334) were found to be predictive of severe subcutaneous fibrosis. On haplotype analysis, the cumulative risk of developing severe fibrosis was observed in patients carrying both haplotypes of variant Homozygous AA genotype of ERCC4 Ex8 (1244G>A, rs1800067) and Homozygous TT genotype of XRCC5 (1401 G>T, rs828907) (p=0.010*, OR 26.340, 95% CI 4.014-76.568).ConclusionWe demonstrated significant associations between single nucleotide polymorphisms of DNA repair genes and radiation-induced subcutaneous fibrosis in patients of oropharyngeal carcinoma treated with radiotherapy. We propose to incorporate these genetic markers into predictive models for identifying patients genetically predisposed to the development of radiation-induced fibrosis, thus guiding personalized treatment protocols.

Single nucleotide polymorphisms (SNPs) of hOGG1 and XRCC1 DNA repair genes and the risk of ovarian cancer in Polish women

Tumor Biology ◽  
2015 ◽  
Vol 36 (12) ◽  
pp. 9457-9463 ◽  
Author(s):  
Magdalena M. Michalska ◽  
Dariusz Samulak ◽  
Hanna Romanowicz ◽  
Jan Bieńkiewicz ◽  
Maciej Sobkowski ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Repair ◽  
Single Nucleotide Polymorphisms ◽  
Dna Repair Genes ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Repair Genes

scholarly journals Polymorphisms of DNA repair genes are associated with colorectal cancer in patients with Lynch syndrome

2018 ◽  
Vol 6 (4) ◽  
pp. 533-540 ◽  
Author(s):  
Abram B. Kamiza ◽  
Ling-Ling Hsieh ◽  
Reiping Tang ◽  
Huei-Tzu Chien ◽  
Chih-Hsiung Lai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Repair ◽  
Lynch Syndrome ◽  
Dna Repair Genes ◽  
Repair Genes

scholarly journals Single Nucleotide Polymorphisms of RecQ1, RAD54L, and ATM Genes Are Associated With Reduced Survival of Pancreatic Cancer

2006 ◽  
Vol 24 (11) ◽  
pp. 1720-1728 ◽  
Author(s):  
Donghui Li ◽  
Marsha Frazier ◽  
Douglas B. Evans ◽  
Kenneth R. Hess ◽  
Christopher H. Crane ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Dna Repair ◽  
Single Nucleotide Polymorphisms ◽  
Cox Regression ◽  
Dna Repair Genes ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Clinical Prognosis ◽  
Repair Genes

Purpose Our goal was to determine whether single nucleotide polymorphisms (SNPs) in DNA repair genes influence the clinical outcome of pancreatic cancer. Patients and Methods We evaluated 13 SNPs of eight DNA damage response and repair genes in 92 patients with potentially resectable pancreatic adenocarcinoma. All patients were treated with neoadjuvant concurrent gemcitabine and radiotherapy with or without a component of induction gemcitabine/cisplatin at The University of Texas M.D. Anderson Cancer Center (Houston, TX) from February 1999 to August 2004 and observed through August 2005. Response to the pretreatment was assessed by evaluating time to tumor progression and overall survival. Kaplan-Meier plot, log-rank test, and Cox regression were used to compare survival of patients according to genotype. Results The RecQ1 A159C, RAD54L C157T, XRCC1 R194W, and ATM T77C genotypes had a significant effect on the overall survival with log-rank P values of .001, .004, .001, and .02, respectively. A strong combined effect of the four genotypes was observed. Patients with none of the adverse genotypes had a mean survival time of 62.1 months, and those with one, two, or three or more at-risk alleles had median survival times of 27.5, 14.4, and 9.9 months, respectively (log-rank P < .001). There is a significant interaction between the RecQ1 gene and other genotypes. All four genes except XRCC1 remained as independent predictors of survival in multivariate Cox regression models adjusted for other clinical predictors. Conclusion These observations support the hypothesis that polymorphic variants of DNA repair genes affect clinical prognosis of patients with pancreatic cancer.

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