Effect of APE1 T2197G (Asp148Glu) Polymorphism on APE1, XRCC1, PARP1 and OGG1 Expression in Patients with Colorectal Cancer

Santos, Juliana C.; Funck, Alexandre; Silva-Fernandes, Isabelle J. L.; Rabenhorst, Sílvia Helena Barem

doi:10.3390/ijms151017333

Cited by 21 publications

(11 citation statements)

References 34 publications

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“…In the present study we found similar results. When evaluating the expression of OGG1 we found reduced expression in tumor tissue, similar to the studies previously cited 32 , 29 . We also found a reduction in the tissue expression of the gene in patients with tumors located in the rectum and in patients classified in more advanced stages of the disease.…”

Section: Discussionsupporting

confidence: 89%

“…They found that, to relate the expression of genes OGG1 and MUTYH when gender, age, location of the tumor histological grade stadiums of the TNM classification (I+II+x+II+IV) found no significant differences 32 . In Brazil, only one study evaluated the behavior of the gene OGG1 in patients with sporadic CRC 29 . Using samples from the same population of patients the authors found a lower expression of OGG1 in tumoral tissue 29 .…”

Section: Discussionmentioning

confidence: 99%

“…In Brazil, only one study evaluated the behavior of the gene OGG1 in patients with sporadic CRC 29 . Using samples from the same population of patients the authors found a lower expression of OGG1 in tumoral tissue 29 . With regard to location of the tumor identified lower gene expression only in patients with cancer of the rectum and in tumors with more advanced stages 29 .…”

Section: Discussionmentioning

confidence: 99%

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Tissue Expresion of the Genes Mutyh and Ogg1 in Patients With Sporadic Colorectal Cancer

Nascimento

Ribeiro

Magro

et al. 2017

ABCD, arq. bras. cir. dig.

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Background: MTUYH and OGG1 genes have importance in the base excision repair systems of oxidized DNA bases. Modification of the tissue expression of these genes is related to the increased risk of developing colorectal cancer. Aim: To evaluate the tissue expression of MUTYH and OGG1 comparing normal and neoplastic tissues of patients with sporadic colorectal cancer and to correlate it with clinical and histopathological variables. Method: MUTYH and OGG1 tissue expression was quantified by RT-PCR in patients with colorectal cancer and the values were compared in normal and neoplastic tissues. MUTYH and OGG1 expression was measured and normalized to the constitutive 18S gene. The level of expression of both genes was correlated with the variables: age, gender, tumor location, size of the tumor, histological type, degree of cell differentiation, invasion depth in the intestinal wall, angiolymphatic infiltration, lymph node involvement and TNM staging. Results: Was found downregulation of both genes in neoplastic when compared to normal tissue. There was downregulation of the MUTYH in larger tumors and in patients with angiolymphatic invasion. Tumors with more advanced TNM stages (III and IV) presented downregulation of both genes when compared to those with earlier stages (I and II). Conclusion: The MUTYH and OGG1 genes present downregulation in the more advanced stages of colorectal cancer.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Tissue Expresion of the Genes Mutyh and Ogg1 in Patients With Sporadic Colorectal Cancer

Nascimento

Ribeiro

Magro

et al. 2017

ABCD, arq. bras. cir. dig.

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“…In the case of BER, published evidence suggests an association between inappropriate BER and increased tumour aggressiveness in CRC [for review see 11]. However, how exactly BER affects tumour malignancy remains to be determined since conflicting results are often reported on the expression of a limited number of BER genes [ 12 , 13 , 14 ]. Despite these limitations, BER modulation is under active investigation as a potential therapeutic approach for chemotherapy sensitization [for review see 15].…”

Section: Introductionmentioning

confidence: 99%

Base excision repair imbalance in colorectal cancer has prognostic value and modulates response to chemotherapy

et al. 2017

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Colorectal cancer (CRC) is prevalent worldwide, and treatment often involves surgery and genotoxic chemotherapy. DNA repair mechanisms, such as base excision repair (BER) and mismatch repair (MMR), may not only influence tumour characteristics and prognosis but also dictate chemotherapy response. Defective MMR contributes to chemoresistance in colorectal cancer. Moreover, BER affects cellular survival by repairing genotoxic base damage in a process that itself can disrupt metabolism. In this study, we characterized BER and MMR gene expression in colorectal tumours and the association between this repair profile with patients’ clinical and pathological features. In addition, we exploited the possible mechanisms underlying the association between altered DNA repair, metabolism and response to chemotherapy. Seventy pairs of sporadic colorectal tumour samples and adjacent non-tumour mucosal specimens were assessed for BER and MMR gene and protein expression and their association with pathological and clinical features. MMR-deficient colon cancer cells (HCT116) transiently overexpressing MPG or XRCC1 were treated with 5-FU or TMZ and evaluated for viability and metabolic intermediate levels. Increase in BER gene and protein expression is associated with more aggressive tumour features and poor pathological outcomes in CRC. However, tumours with reduced MMR gene expression also displayed low MPG, OGG1 and PARP1 expression. Imbalancing BER by overexpression of MPG, but not XRCC1, sensitises MMR-deficient colon cancer cells to 5-FU and TMZ and leads to ATP depletion and lactate accumulation. MPG overexpression alters DNA repair and metabolism and is a potential strategy to overcome 5-FU chemotherapeutic resistance in MMR-deficient CRC.

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“…DNA repair genes play a critical role in maintaining genome integrity and repairing this damage. Currently, there is increasing evidence that gene analysis reveals the importance of DNA repair genes and that polymorphisms, such as the XRCC1 polymorphisms R399Q and R280H, are associated with different human cancers, such as bladder cancer, breast cancer, colorectal cancer, lung cancer, and endometrial carcinoma 16 33 34 35 36 . These polymorphisms have also been explored in numerous studies for an association with prostate cancer, with conflicting results.…”

Section: Discussionmentioning

confidence: 99%

Meta-Analysis of the Relationship between XRCC1-Arg399Gln and Arg280His Polymorphisms and the Risk of Prostate Cancer

Yan

Wang

Tao

et al. 2015

Sci Rep

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Prostate cancer is one of the most common noncutaneous malignancies in Western countries. Because there has been a debate regarding the relationship between the XRCC1-Arg399Gln and Arg280His polymorphisms and prostate cancer risk, we therefore performed this meta-analysis. The electronic databases PubMed, EMBASE, and Medline were searched prior to October 1, 2014. An odds ratio and 95% confidence interval were used to calculate association. Heterogeneity was tested by both a chi-square test and I2statistic. Funnel plots and Egger’s test were used to assess publication bias. All statistical analyses were performed using STATA 12.0 software. A significant association between the XRCC1-Arg399Gln polymorphism and prostate cancer risk was found under a homozygote model and a recessive model. A significant association between XRCC1-Arg280His and prostate cancer risk was found under a heterozygote model, a recessive model, and a dominant model. Overall, the results of this meta-analysis show that the XRCC1-Arg399Gln polymorphism may be associated with an increased risk for prostate cancer under the homozygote model and the recessive model. And XRCC1-Arg280His polymorphism is likely to be related with prostate cancer risk under the heterozygote model and the dominant model. Additional larger well-designed studies are needed to validate our results.

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Effect of APE1 T2197G (Asp148Glu) Polymorphism on APE1, XRCC1, PARP1 and OGG1 Expression in Patients with Colorectal Cancer

Cited by 21 publications

References 34 publications

Tissue Expresion of the Genes Mutyh and Ogg1 in Patients With Sporadic Colorectal Cancer

Tissue Expresion of the Genes Mutyh and Ogg1 in Patients With Sporadic Colorectal Cancer

Base excision repair imbalance in colorectal cancer has prognostic value and modulates response to chemotherapy

Meta-Analysis of the Relationship between XRCC1-Arg399Gln and Arg280His Polymorphisms and the Risk of Prostate Cancer

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