<i>XPA</i> gene polymorphisms and risk of neuroblastoma in Chinese children: a two-center case-control study

Ji, Tao; Zhang, Zhuo; Su, Meng; Yan, Lizhao; He, Jing; Zhang, Jiao

doi:10.7150/jca.25973

Cited by 4 publications

(1 citation statement)

References 55 publications

(51 reference statements)

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“…In contrast to A23G SNP, the G709A SNP has virtually no impact on the repair of UV-and benzo(a)pyrene diol epoxide-induced DNA damage compared to wild-type XPA [186,187], and appears to have a protective effect for LC patients [166][167][168]. [154,155,159,[166][167][168][169][170][171][172][173][174][175][176][177][178][179][180]185,[191][192][193] Three further SNPs reside in intron sequences of XPA: rs3176658, which causes C to T transition, rs3176721, a C to A transversion, and rs2808667, a T to C transition (www.ncbi.nlm.nih.gov/snp). rs3176658 and rs3176721 are associated with efficacy of platinum-based chemotherapy in LC [188], while rs3176658 alone has been shown to be significantly associated with LC risk [189] and with response to neoadjuvant radiochemotherapy treatment of locally advanced rectal cancer (RC) [190].…”

Section: Xpa Polymorphisms and Cancer Incidence And Treatment Outcomementioning

confidence: 99%

XPA: DNA Repair Protein of Significant Clinical Importance

Pulzová¹,

Ward

Chovanec³

2020

IJMS

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The nucleotide excision repair (NER) pathway is activated in response to a broad spectrum of DNA lesions, including bulky lesions induced by platinum-based chemotherapeutic agents. Expression levels of NER factors and resistance to chemotherapy has been examined with some suggestion that NER plays a role in tumour resistance; however, there is a great degree of variability in these studies. Nevertheless, recent clinical studies have suggested Xeroderma Pigmentosum group A (XPA) protein, a key regulator of the NER pathway that is essential for the repair of DNA damage induced by platinum-based chemotherapeutics, as a potential prognostic and predictive biomarker for response to treatment. XPA functions in damage verification step in NER, as well as a molecular scaffold to assemble other NER core factors around the DNA damage site, mediated by protein–protein interactions. In this review, we focus on the interacting partners and mechanisms of regulation of the XPA protein. We summarize clinical oncology data related to this DNA repair factor, particularly its relationship with treatment outcome, and examine the potential of XPA as a target for small molecule inhibitors.

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Section: Xpa Polymorphisms and Cancer Incidence And Treatment Outcomementioning

confidence: 99%

XPA: DNA Repair Protein of Significant Clinical Importance

Pulzová¹,

Ward

Chovanec³

2020

IJMS

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APEX1 Polymorphisms and Neuroblastoma Risk in Chinese Children: A Three-Center Case-Control Study

Liu

Jia

Hua

et al. 2019

Oxidative Medicine and Cellular Longevity

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Neuroblastoma is a life-threatening extracranial solid tumor, preferentially occurring in children. However, its etiology remains unclear. APEX1 is a critical gene in the base excision repair (BER) system responsible for maintaining genome stability. Given the potential effects of APEX1 polymorphisms on the ability of the DNA damage repair, many studies have investigated the association between these variants and susceptibility to several types of cancer but not neuroblastoma. Here, we conducted a three-center case-control study to evaluate the association between APEX1 polymorphisms (rs1130409 T>G, rs1760944 T>G, and rs3136817 T>C) and neuroblastoma risk in Chinese children, consisting of 469 cases and 998 controls. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated to evaluate the associations. No significant association with neuroblastoma risk was found for the studied APEX1 polymorphisms in the single locus or combination analysis. Interestingly, stratified analysis showed that rs1130409 GG genotype significantly reduced the risk of tumor in males. Furthermore, we found that carriers with 1-3 protective genotypes had a lower neuroblastoma risk in the children older than18 months and male, when compared to those without protective genotypes. In summary, our data indicate that APEX1 gene polymorphisms may have a weak effect on neuroblastoma susceptibility. These findings should be further validated by well-designed studies with larger sample size.

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Association of human XPA rs1800975 polymorphism and cancer susceptibility: an integrative analysis of 71 case–control studies

Yuan

2020

Cancer Cell Int

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Background: The objective of the present study is to comprehensively evaluate the impact of the rs1800975 A/G polymorphism within the human xeroderma pigmentosum group A (XPA) gene on susceptibility to overall cancer by performing an integrative analysis of the current evidence. Methods: We retrieved possible relevant publications from a total of six electronic databases (updated to April 2020) and selected eligible case-control studies for pooled assessment. P-values of association and odds ratio (OR) were calculated for the assessment of association effect. We also performed Begg's test and Egger's test, sensitivity analysis, false-positive report probability (FPRP) analysis, trial sequential analysis (TSA), and expression/splicing quantitative trait loci (eQTL/sQTL) analyses. Results: In total, 71 case-control studies with 19,257 cases and 30,208 controls from 52 publications were included for pooling analysis. We observed an enhanced overall cancer susceptibility in cancer cases compared with negative controls in the Caucasian subgroup analysis for the genetic models of allelic G vs. A, carrier G vs. A, homozygotic GG vs AA, heterozygotic AG vs. AA, dominant AG + GG vs. AA and recessive GG vs. AA + AG (P < 0.05, OR > 1). A similar positive conclusion was also detected in the "skin cancer" or "skin basal cell carcinoma (BCC)" subgroup analysis of the Caucasian population. Our FPRP analysis and TSA results further confirmed the robustness of the conclusion. However, our eQTL/sQTL data did not support the strong links of rs1800975 with the gene expression or splicing changes of XPA in the skin tissue. In addition, even though we observed a decreased risk of lung cancer under the homozygotic, heterozygotic and dominant models (P < 0.05, OR < 1) and an enhanced risk of colorectal cancer under the allelic, homozygotic, heterozygotic, dominant (P < 0.05, OR > 1), our data from FPRP analysis and another pooling analysis with only the population-based controls in the Caucasian population did not support the strong links between the XPA rs1800975 A/G polymorphism and the risk of lung or colorectal cancer. Conclusions: Our findings provide evidence of the close relationship between the XPA rs1800975 A/G polymorphism and susceptibility to skin cancer in the Caucasian population. The potential effect of XPA rs1800975 on the risk of developing lung or colorectal cancer still merits the enrollment of larger well-scaled studies.

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XPA gene polymorphisms and risk of neuroblastoma in Chinese children: a two-center case-control study

Cited by 4 publications

References 55 publications

XPA: DNA Repair Protein of Significant Clinical Importance

XPA: DNA Repair Protein of Significant Clinical Importance

APEX1 Polymorphisms and Neuroblastoma Risk in Chinese Children: A Three-Center Case-Control Study

Association of human XPA rs1800975 polymorphism and cancer susceptibility: an integrative analysis of 71 case–control studies

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