DNA base excision repair genes variants rs25487 (X-ray repair cross-complementing 1) and rs1052133 (human 8-oxoguanine glycosylase 1) with susceptibility to ovarian cancer in the population of the Jammu region, India

Background: Ovarian cancer is highly prevalent in the population of Jammu, in India; the ovarian cancer ranks third among other types of cancer prevalent in females. However, association studies on ovarian cancer are lacking in this region. We aimed to investigate the disease susceptible variants rs1052133 (human 8-oxoguanine glycosylase 1 [hOGG1]) and rs25487 (X-ray repair cross-complementing 1 [XRCC1]) with ovarian cancer in population of Jammu, India. Materials and Methods: The study conducted in the Shri Mata Vaishno Devi University is a 3-year study which included a total of 280 well-characterized samples (130 ovarian cancer cases and 150 healthy controls). hOGG1 and XRCC1 polymorphisms were determined by polymerase chain reaction-based restriction fragment length polymorphism, and these genotyping results were confirmed by Sanger sequencing. Hardy–Weinberg equilibrium for both single-nucleotide polymorphisms (SNPs) was assessed using the Chi-square test. The allele and genotype-specific risks were estimated by odds ratios with 95% confidence intervals. Results: In this preliminary study, SNP rs1052133 showed protection with ovarian cancer (P = 0.042). The SNP rs25487 was not found associated with ovarian cancer (P = 0.271). Conclusion: Our results indicate that the G allele of rs1052133 imparts protection to the population whereas variant rs25487 was not associated with ovarian cancer in population from the Jammu region, indicating that larger sample size is needed for further statistical validation. Further, association of other SNPs in these genes should also be carried out as their role cannot be ruled out.

Genetic polymorphisms of hOGG1 in the 5'-flank region in population of radon exposure area in Guangdong Province / 中国职业医学

OBJECTIVE: To screen genetic polymorphisms in the 5'-flank region of 8-hydroxyguanine DNA glycosylase( hOGG1) gene and analyze the characteristics of their genetic distribution in Han population of radon exposure area in Guangdong Province. METHODS: A simple random sampling method was used to select 60 subjects as radon exposure population. The genomic DNA samples were extracted from peripheral blood. The single nucleotide at-1721 nt-+ 164 nt locus of hOGG1 were screened using polymerase chain reaction( PCR) amplification,purification and direct sequencing for polymorphisms. Genetic characteristics of single nucleotide polymorphisms( SNP) in the study population were analyzed and compared with different populations reported in Hap Map data. RESULTS: The 5'-flank region of hOGG1 were amplified and sequenced in these 60 individuals( 120 chromosomes) of healthy Han Chinese in radon exposure area. Eight SNPs were identified by sequence alignment in the study population. Among them,there was 3 known polymorphisms and their minor allele frequencies( MAF) were-1493 G > A( 4. 2%),-834 G > C( 0. 8%) and-18 G > T( 3. 3%),respectively. The MAF of other 5 novel variations were-1455 G > A( 0. 8%),-1293 A > T( 23. 3%),-1187 C > A( 7. 5%),-337 C > A( 36. 7%) and-323 G > A( 0. 8%),respectively. The differences in the MAF distribution of-1493 G > A between the study population and the Hap Map-CEU were statistically significant( P < 0. 05). CONCLUSION: Eight SNPs and their genetic characteristics were screened and identified in the 5'-flank region of hOGG1 of Han Chinese population in radon exposure area. This result provides a basis for construction of polymorphism haplotypes and functional analysis for the target population.

Phototherapeutic modalities pose no significantly increased risk of oxidative damage to DNA in dark skinned individuals.

Background: 8‑oxoguanine, a major product of DNA oxidation, is considered a key parameter in measuring the carcinogenic effects of ultraviolet radiation. Objective: To assess and compare the carcinogenic potential of different photo (chemo) therapeutic modalities in photoresponsive skin diseases by measuring the levels of 8‑oxoguanine in dark‑skinned individuals before and after photo (chemo) therapy. Methods: A prospective, randomized controlled pilot study was conducted in 63 patients of skin types III–V with photo‑responsive dermatoses including vitiligo, psoriasis and mycosis fungoides. Patients were divided into three groups; Group 1 (received narrowband ultraviolet‑B), Group 2 (received psoralen plus ultraviolet‑A) and Group 3 (received broadband ultraviolet‑A). Biopsies were taken before and after phototherapy to measure 8‑oxoguanine levels using enzyme‑linked immunosorbent assay. Biopsies were also taken from the sun‑protected skin in 21 controls subjects who had no dermatological disease. Results: Regardless of the disease, a significantly higher level of 8‑oxoguanine was found after treatment when compared to the pre‑treatment baseline levels; however, these levels were comparable to those in control subjects. A weakly significant positive correlation was found between cumulative dose and 8‑oxoguanine levels following psoralen plus ultraviolet‑A therapy. In controls, comparing the 8‑oxoguanine levels between skin types III and IV showed significantly lower 8‑oxoguanine in skin type IV. Conclusion: Therapeutic doses of ultraviolet radiation are relatively safe in dark skinned patients; however, minimizing the cumulative dose of phototherapeutic modalities (particularly psoralen plus ultraviolet‑A) is recommended.

Identification of Escherichia coli 8-oxoguanine endonuclease

7,8-Dihydro-8-oxoguanine (oh8Gua) endonuclease is a DNA repair enzyme in Escherichia coli to remove oh8Gua, a promutagenic DNA adduct. Due to the unique mode of enzyme action and substrate specificity, this DNA repair enzyme has been suggested to be identical to 2,6-diamino-4-hydroxyformamidopyrimidine (Fapy)-DNA glycosylase (Fpg). However, oh8Gua endonuclease had not been definitely identified because it had not been homogeneously purified. In this study, we attempted to purify and identify the enzyme. Through several purification procedures, we obtained two proteins (32 kD and 29 kD). The larger protein co-migrated with Fpg in 12% SDS-PAGE gel. Sequences of N-terminal amino acids of these two proteins were identical to that of Fpg; the smaller one is a degraded product of oh8Gua endonuclease during purification steps. These results indicate that oh8Gua endonuclease is identical to Fpg, implying that oh8Gua in oxidatively damaged DNA rather than Fapy is more physiologically relevant substrate for Fpg.