Association of DNA Repair Genes XRCC1 and APE-1 with the Risk of Cervical Cancer in North Indian population

Abstract

Backgrounds: Cervical cancer (CC) is one of the leading cause of death in women worldwide, HPV infection is the major risk factor in the disease development, 0and however other risk factor such as chemical carcinogens, genetic susceptibility and altered immune system are also a cause of the disease progression. In the light of the above statement we studied the base excision repair pathway (BER). Methods: We identified and studied the association of Single Nucleotide polymorphisms in the DNA repair genes of XRCC1 ( Arg194Trp, Arg399G ,) and APE-1Asp/148Glu to the susceptibility of cervical cancer (CC) in North Indian population. In our study of cases (n=102). Controls (n=109) were recruited from among women without cervical abnormalities. Genotypes were determined by PCR-CTPP method, Taking DNA from peripheral blood in a case control study. Results: A positive association was observed between the polymorphisms of XRCC1 genes, that is, in codons 194 (P=0.03, odds ratio (OR) =2.39, 95% confidence interval (CI)=5.2–1.1), 280 (P=0.01, OR=4.1, 95% CI=11.5–1.3) and 399 (P=0.01, OR=3.4, 95% CI=8.6–1.3) while APE-1 genotype GG (p=0.03,odds ratio(OR)=0.2,95% confidence interval (CI)=0.97-0.004) we observed a statistically significant protective role in developing cervical cancer. Conclusion: Our results suggested that, XRCC1 gene is an important candidate gene for susceptibility to cervical cancer. Although the sample size was small, the present study indicate a statistical association between cervical cancer and XRCC1 SNPs . Future studies are needed that may provide a better understanding of the association between gene polymorphism and cervical carcinoma risk.

Genetic polymorphisms in DNA repair genes and their association with risk of cervical cancer: A systematic review and meta‐analysis

“…[1][2][3][4][6][7][8]12,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] N = 19 studies 3,4,6,7,12,[15][16][17]19,20,22,23,[25][26][27][29][30][31][32] were included regarding association between genetic polymorphisms in XRCC1 and cervical cancer (including n = 3874 cases and 4891 controls), n = 7 studies (including n = 1325 cases and 1273 controls) 2,3,12,18,26,29,…”

“…In addition, n = 2 studies (including n = 678 cases and 1122 controls) 18,28 for ERCC5, n = 1 study (including n = 131 cases and 320 controls) 16 for 8-oxoguanineDNA glycosylase (OGG)1, n = 1 study (including n = 98 cases and 123 controls) 1 for ribonuclease L (RNASEL), n = 1 study (including n = 469 cases and 452 controls) 20 for Fanconi anemia complementation group A (FANCA), n = 1 study (including n = 469 cases and 452 controls) 20 for exonuclease 1 (EXO1), n = 1 study (including n = 469 cases and 452 controls) 20 for cytochrome B-245 alpha chain (CYBA), n = 2 studies (including n = 332 cases and 413 controls) 26,29 for cyclin dependent kinase inhibitor 1A (CDKN1A), n = 2 studies (including n = 1537 cases and 1502 controls) 8,21 for breast cancer 1 (BRCA1), n = 1 study (including n = 404 cases and 404 controls) 21 for BRCA1 associated RING domain 1 (BARD1), n = 1 study (including n = 80 cases and 177 controls) 25 for poly (ADP-ribose) polymerase-1 (PARP1) and n = 1 study (including n = 102 cases and 109 controls) 7 for Apurinic/Apyrimidinic endonuclease 1 (APE1) were included in the present study. Association between polymorphisms of XRCC1 and risk of cervical cancer N = 9 studies (including n = 1574 cases and 2129 controls) 3,6,7,12,15,17,25,27,30 1 and Figure 1). Sensitivity analysis indicated no changes in the direction of effect when anyone study was eliminated in all meta-analyses (Figure S2).…”

“…In addition, no significant risks of publication bias were showed by Begg's test, Egger's tests, and funnel plots in all these analyses (Table S3 and Figure S5). N = 19 studies 3,4,6,7,12,[15][16][17]19,20,22,23,[25][26][27][29][30][31][32] (including n = 3874 cases and 4891 controls) explored the association between XRCC1 Arg399Gln polymorphisms and risk of cervical cancer. There were significant associations between XRCC1 Arg399Gln polymorphisms and risk of cervical cancer in total population under all four genetic models (GA vs. GG: OR = 1.22, 95%CI 1.05-1.42, I 2 = 53.8%, p value of Q test = 0.003; AA vs. GG: OR = 1.93, 95%CI 1.33-2.80, I 2 = 75.7%, p value of Q test <0.001; GA + AA vs. GG: OR = 1.33, 95%CI 1.12-1.57, I 2 = 66.3%, p value of Q test <0.001; AA vs. GG + GA: OR = 1.65, 95%CI 1.19-2.28, I 2 = 69.6%, p value of Q test <0.001; A vs. G: OR = 1.33, 95%CI 1.12-1.57, I 2 = 80.1%, p value of Q test <0.001) (Table 1 and Figure 3).…”

“…5 Noteworthy, due to the organized cancer screening programs and HPV vaccination, the incidence and mortality rates of cervical cancer have been gradually decreased in developed countries, while approximately 90% of new cases and deaths of cervical cancers occur in low and middle-income countries such as South Africa, India, China, and Brazil. [6][7][8] According to the prediction of the World Health Organization (WHO), the number of new cancer cases will raise rapidly in lowincome countries with the increase of world population and life expectancy if there are no effective interventions. 7 DNA repair plays an essential role in defense against genotoxic stress that may result in inflammation, cancer, and metabolic changes, and is critical in the prevention of tumorigenesis.…”

“…[6][7][8] According to the prediction of the World Health Organization (WHO), the number of new cancer cases will raise rapidly in lowincome countries with the increase of world population and life expectancy if there are no effective interventions. 7 DNA repair plays an essential role in defense against genotoxic stress that may result in inflammation, cancer, and metabolic changes, and is critical in the prevention of tumorigenesis. 9,10 One of the most common genetic events in hereditary cancers is the defects in DNA repair genes.…”