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      Is Open Access

      The ECCR1 rs11615, ERCC4 rs2276466, XPC rs2228000 and XPC rs2228001 polymorphisms increase the cervical cancer risk and aggressiveness in the Bangladeshi population

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          Abstract

          Background

          Multiple studies around the world revealed that genetic polymorphism in different genes of the DNA repair system might affect the DNA repair capabilities and accelerate the chances of cervical cancer (CC) development. Therefore, we aimed to evaluate the association of DNA repair gene- ECCR1 rs11615, ERCC4 rs2276466, XPC rs2228000 and rs2228001 polymorphisms and CC susceptibility in the Bangladeshi population.

          Methods

          A case-control genetic association study was conducted among 210 patients with diagnostically confirmed CC and 200 healthy volunteers. The p-value and OR (odds ratios) with 95% CI (confidence interval) were evaluated to get the level of association.

          Results

          After the individual analysis of all SNPs, we noticed that ECCR1 rs11615 possessed a significantly lower risk, whereas ERCC4 rs2276466 possessed a significantly elevated risk of CC in all genetic models ( p < 0.05). XPC rs2228000 showed a significantly lower risk of CC in TC, TC + CC genotypes and allele model (OR = 0.61, p = 0.025; OR = 0.61, p = 0.019 and OR = 0.67, p = 0.027, respectively), whereas XPC rs2228001 possessed a significantly elevated risk of CC in CA, CA + AA genotypes and allele model (OR = 1.67, p = 0.012; OR = 1.69, p = 0.009 and OR = 1.42, p = 0.022). Besides, ERCC4 rs2276466 (Grade III vs. I + II: OR = 4.01, p = 0.003) and XPC rs2228001 (Grade III vs. I + II: OR = 3.38, p = 0.003) were connected with high tumor aggressiveness and ERCC4 rs2276466 was also showed a lower risk of CC development in the younger population (<45 years).

          Conclusion

          The findings supported that rs2276466 and rs2228001 polymorphisms increase CC development and aggressiveness, whereas rs11615 and rs2228000 lower the CC risk in the studied population.

          Abstract

          Cervical cancer, Single nucleotide polymorphism, ECCR1, ERCC4, XPC, Bangladeshi ethnicity.

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          Most cited references45

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          The DNA-damage response in human biology and disease.

          The prime objective for every life form is to deliver its genetic material, intact and unchanged, to the next generation. This must be achieved despite constant assaults by endogenous and environmental agents on the DNA. To counter this threat, life has evolved several systems to detect DNA damage, signal its presence and mediate its repair. Such responses, which have an impact on a wide range of cellular events, are biologically significant because they prevent diverse human diseases. Our improving understanding of DNA-damage responses is providing new avenues for disease management.
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            Base excision repair.

            Base excision repair (BER) corrects DNA damage from oxidation, deamination and alkylation. Such base lesions cause little distortion to the DNA helix structure. BER is initiated by a DNA glycosylase that recognizes and removes the damaged base, leaving an abasic site that is further processed by short-patch repair or long-patch repair that largely uses different proteins to complete BER. At least 11 distinct mammalian DNA glycosylases are known, each recognizing a few related lesions, frequently with some overlap in specificities. Impressively, the damaged bases are rapidly identified in a vast excess of normal bases, without a supply of energy. BER protects against cancer, aging, and neurodegeneration and takes place both in nuclei and mitochondria. More recently, an important role of uracil-DNA glycosylase UNG2 in adaptive immunity was revealed. Furthermore, other DNA glycosylases may have important roles in epigenetics, thus expanding the repertoire of BER proteins.
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              A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis.

              XPF-ERCC1 endonuclease is required for repair of helix-distorting DNA lesions and cytotoxic DNA interstrand crosslinks. Mild mutations in XPF cause the cancer-prone syndrome xeroderma pigmentosum. A patient presented with a severe XPF mutation leading to profound crosslink sensitivity and dramatic progeroid symptoms. It is not known how unrepaired DNA damage accelerates ageing or its relevance to natural ageing. Here we show a highly significant correlation between the liver transcriptome of old mice and a mouse model of this progeroid syndrome. Expression data from XPF-ERCC1-deficient mice indicate increased cell death and anti-oxidant defences, a shift towards anabolism and reduced growth hormone/insulin-like growth factor 1 (IGF1) signalling, a known regulator of lifespan. Similar changes are seen in wild-type mice in response to chronic genotoxic stress, caloric restriction, or with ageing. We conclude that unrepaired cytotoxic DNA damage induces a highly conserved metabolic response mediated by the IGF1/insulin pathway, which re-allocates resources from growth to somatic preservation and life extension. This highlights a causal contribution of DNA damage to ageing and demonstrates that ageing and end-of-life fitness are determined both by stochastic damage, which is the cause of functional decline, and genetics, which determines the rates of damage accumulation and decline.
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                Author and article information

                Contributors
                Journal
                Heliyon
                Heliyon
                Heliyon
                Elsevier
                2405-8440
                09 January 2021
                January 2021
                09 January 2021
                : 7
                : 1
                : e05919
                Affiliations
                [a ]Department of Pharmacy, University of Asia Pacific, Dhaka 1205, Bangladesh
                [b ]Department of Pharmacy, Noakhali Science and Technology University, Sonapur, Noakhali 3814, Bangladesh
                Author notes
                []Corresponding author. research_safiq@ 123456yahoo.com
                Article
                S2405-8440(21)00024-4 e05919
                10.1016/j.heliyon.2021.e05919
                7809183
                33490679
                e8ff4524-bf57-434d-bdf1-ca8e83e0ac37
                © 2021 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 17 October 2020
                : 7 December 2020
                : 5 January 2021
                Categories
                Research Article

                cervical cancer,single nucleotide polymorphism,eccr1,ercc4,xpc,bangladeshi ethnicity

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