Publication: Genetic polymorphisms of xrcc1 on cervical cancer susceptibility risk
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Date
2022
Authors
Hamid, Mohd Ridzuan
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Abstract
Background: Cervical cancer was ranked fourth as the most frequently diagnosed cancer worldwide and the fourth leading cause of cancer mortality among women. DNA repair mechanism plays a major role in protecting cells against DNA damage and carcinogenesis. It is well known that the DNA repair gene has become an important determinant of cancer risk. Genetic polymorphisms among the genes which are involved in DNA damage response may contribute to an augmented risk of cancer development including cervical cancer. X-ray repair cross-complimenting protein 1 (XRCC1) is a nuclear protein that is one of the key nonenzymatic scaffolding proteins involved in base excision repair (BER). Inter-individual genetic variations such as single nucleotide polymorphisms (SNPs) of XRCC1 Arg399Gln G>A (rs25487) and XRCC1 Arg194Trp C>T (rs1799782) may reduce the XRCC1 activity in repairing DNA damage and thus may increase the cancer risk predisposition. Knowledge and scientific evidence on the frequency of XRCC1 Arg399Gln G>A (rs25487) and XRCC1 Arg194Trp C>T (rs1799782) among cervical cancer patients is considerably limited. Therefore, this research was conducted to fill this knowledge gap by investigating the impact of XRCC1 polymorphisms on cervical cancer susceptibility risk. Methods: In this study, 133 cervical cancer patients and 133 healthy female control individuals were enrolled. The genotyping of XRCC1 Arg399Gln G>A (rs25487) and XRCC1 Arg194Trp C>T (rs1799782) was performed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Next, the genotype patterns were categorized into homozygous wildtype, heterozygous and homozygous variant. The genotype and allele frequencies of both XRCC1 polymorphisms were calculated and compared between cervical cancer patients and healthy individual group using chi-square test. Next, logistic regression analysis deriving Odds Ratio (OR) with 95% CI was performed to elucidate the cervical cancer susceptibility risk. Results: We found a significant association of genetic polymorphism in XRCC1 Arg399Gln G>A (rs25487) with cervical cancer susceptibility risk. The heterozygous (GA) genotype of XRCC1 Arg399Gln G>A (rs25487) showed significantly higher risk for cervical cancer susceptibility with OR: 2.325, 95% CI: (1.380-3.918) and p-value of 0.002. However no significant association was observed for XRCC1 Arg194Trp C>T (rs1799782) with cervical cancer susceptibility risk. Conclusion Our study demonstrated an association between genetic polymorphisms in one of DNA repair pathway (BER) gene XRCC1 Arg399Gln G>A (rs25487) with susceptibility risk of cervical cancer patients. The positive association from this research study may be considered to be applied as a screening tool for early detection in cervical cancer patient in the future. However no significant association was observed for XRCC1 Arg194Trp C>T (rs1799782) with cervical cancer susceptibility risk. Although a prospective study with a larger patient population and involvement of multiple SNPs and genes necessary to validate this findings, our findings provides preliminary data locally and opportunity for future study
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Keywords
Cervical cancer , XRCC1 gene polymorphism