Search

Background: 8-Oxo-7, 8-dihydro-2'-deoxyguanosine (8-oxodG) is a potent DNA damage marker that leads to cellular oxidative stress. It is a DNA-repair enzyme that participates in "8-oxodG" DNA adducts removal. Previous studies show weak associations of rs1052133 (hOGG1) in breast cancer patients of Northern India. We performed this study to explore the variant rs1052133 (hOGG1) with breast in the population of Jammu and Kashmir (J and K).Method: A polymerase chain reaction-restriction fragment length polymorphism -based single-nucleotide polymorphism (SNP) genotypic study was carried out in peripheral blood samples of 165 breast cancer patients and 200 healthy controls, using specific primers. Sanger sequencing verified the results.Results: hOGG1-Ser326Cys polymorphism occurred frequently in cases as compared with controls. Data were evaluated by SPSS V.13 software, following Hardy-Weinberg equilibrium (P = 0.002 at OR 2.57; 95% CI [1.68-3.93]), which showed that the SNP rs1052133 had a significant association with increased risk of breast cancer.Conclusion: Overall, the results of this analysis show that the hOGG1-Ser326Cys polymorphism may be associated with an increased risk for breast cancer in the J and K population. [ABSTRACT FROM AUTHOR]

Background & objectives: XRCCI, a major DNA repair gene, acts as a scaffold of different activities involved in repair by interacting with components of base excision repair (BERI at the site of damage. Polymorphisms in this gene are associated with variations in the repair efficiency which might predispose an individual to cancer risk. To associate a gene polymorphism with disease risk, it is imperative to have the data for its genotype distribution in normal population. The present study was therefore carried out to find distribution of XRCCI polymorphisms (codons 194, 280 and 399) in normal north Indian population. Methods: Healthy volunteers hailing from north India (150) were enrolled in the study. DNA was isolated from blood samples and genotyping of codons 194, 280 and 399 of XRCCI gene was done by PCR-restriction fragment length polymorphism (RFLP), using specific primers. Results: The frequencies obtained for heterozygous genotype of codons 194 and 399 were 45 and 49 per cent respectively and were higher than wild and variant genotypes. For codon 280, the highest frequency (59%) was obtained for the wild genotype. Frequencies of the variant genotypes of codons 194 and 399 were higher in males and females respectively. The allele frequencies also followed the similar trends. Interpretation & conclusions: A significant distribution of variant and heterozygous XRCCI genotypes was noticed that warrants further studies on the association between these genotypes and disease risk in our study population. [ABSTRACT FROM AUTHOR]

Pesticide-induced DNA damage is primarily repaired by base excision repair (BER) pathway. However, polymorphism in DNA repair genes may modulate individual's DNA repair capacity (DRC) leading to increased genotoxicity and adverse health effects. Our first study in North-West Indian population aimed to evaluate the impact of OGG1 rs1052133 (Ser326Cys; C1245G), XRCC1 rs1799782 (Arg194Trp; C26304T) and XRCC1 rs25487 (Arg399Gln; G28152A) polymorphisms on the modulation of pesticide-induced DNA damage in a total of 450 subjects (225 pesticide-exposed agricultural workers and 225 age- and sex-matched controls). DNA damage was estimated by alkaline comet assay using silver-staining method. Genotyping was carried out by PCR-RFLP using site-specific restriction enzymes. Mann-Whitney U-test revealed elevation in DNA damage parameters ( p  < 0.01) in pesticide-exposed agricultural workers than controls. Chi-square test showed significant ( p  < 0.05) differences in the XRCC1 Arg194Trp (C26304T) and Arg399Gln (G28152A) genotypes among two groups. Multivariate logistic-regression analysis revealed that heterozygous genotypes of OGG1 rs1052133 (326Ser/Cys; 1245CA), XRCC1 rs1799782 (194Arg/Trp; 26304CT) and XRCC1 rs25487 (399Arg/Gln; 2815GA) were positively associated ( p  < 0.05) with elevated DNA damage parameters in pesticide-exposed agricultural workers. Our results strongly indicate significant positive association of variant OGG1 and XRCC1 genotypes with reduced DRC and higher pesticide-induced DNA damage in North-West Indian agricultural workers.

Aim: The DNA repair system safeguards integrity of DNA. Genetic alterations force the improper repair which in conjugation with other factors ultimately results in carcinogenesis. Materials & methods: PCR-restriction fragment length polymorphism was used for genotyping, which was followed by statistical analysis using logistic regression analysis, multifactor dimensionality reduction and classification and regression analysis tree, elaborating the association with lung cancer subjects. Results: Combination of XRCC1 632 and OGG1326 showcased a high risk of eightfold (odds ratio: 7.92; 95% CI: 2.68-23.4; p = 0.0002; false discovery rate (FDR) p = 0.002). Similarly, XRCC1 632 and MUTYH 324 (odds ratio: 5.07; 95% CI: 2.6-9.67; p < 0.0001; FDRp = 0.002) had a high risk. Multifactor dimensionality reduction analysis revealed five factor model as the best model with prediction error of 0.37 (p = 0.02). Conclusion: There was a clear indication that high order interactions were major role players in the study.