DNA repair genes are important in maintaining genomic stability and integrity. DNA repair gene polymorphisms, such as those of the human homolog of 8-oxoguanine DNA glycosylase 1 (hOGG1) and excision repair cross-complementing rodent repair deficiency, complementation group 2/Xeroderma pigmentosum complementation group D (ERCC2/XPD), contribute to carcinogenesis. The aim of this study was to investigate the association of prostate cancer (PCa) risk with hOGG1 and ERCC2/XPD genetic variants. A case-control study of 200 cases including 100 PCa patients and 100 healthy subjects was conducted. Two single-nucleotide polymorphisms (SNPs) (ERCC2/XPD Arg156Arg and hOGG1 Ser326Cys) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results demonstrated a significant association of the XPD156 homozygous (AA, OR=3.80; 95% CI: 1.19-12.18; P=0.017), heterozygous (AC, OR=2.48; 95% CI: 1.02-6.35; P=0.033) and combined (AA+AC, OR=2.76; 95% CI: 1.18-6.84; P=0.011) mutant genotypes with a predisposition to high-risk PCa. In the stratified analysis, predisposition to high-risk PCa was also associated with the mutant genotypes of hOGG1 326 homozygous mutant (GG, OR=2.93; 95% CI: 1-8.74; P=0.033). The results also showed that the A allele of XPD Arg156Arg and the G allele of hOGG1 Ser326Cys were associated with an increased risk of PCa (OR=1.86 and 1.62; 95% CI: 1.13-3.06 and 1-2.67, respectively). In conclusion, the findings of this study demonstrated that the ERCC2/XPD Arg156Arg and hOGG1 Ser326Cys polymorphisms increased the susceptibility to high-risk PCa.

https://www.spandidos-publications.com/10.3892/br.2013.123/download

Susceptibility of XPD and hOGG1 genetic variants to prostate cancer.

Background: The human 8-oxoguanine DNA glycosylase (hOGG1) gene may be linked with cancer susceptibility. The aim of this study was to quantitatively summarize any association between the hOGG1 Ser326Cys polymorphism and breast cancer (BC) risk. Materials and Methods: A comprehensive search of the PubMed, Embase, and ISI web of knowledge databases for papers published before 1 October 2016 was conducted. Summary odds ratios (ORs) with corresponding 95 % confidence intervals (95 %CIs) were estimated, with fixed-effects or random-effects models when appropriate, to assess any association. Results: A total of 9,434 cases and 10,497 controls from 18 studies were included in this meta-analysis. When the eligible studies were pooled, there was no evidence found for a significant association between the hOGG1 Ser326Cys polymorphism and BC in in all genetic contrast models G vs. C (OR=1.19, 95% CI 0.92– 1.53), CG vs. CC (OR = 0.97, 95% CI 0.91-1.04, p = 0.46), GG vs. CC (OR = 1.11, 95% CI 0.91-1.35, p = 0.30), GG + CG vs. CC (OR = 0.98, 95% CI 0.92-1.05, p = 0.67), and GG vs. CG + CC (OR = 1.22, 95% CI 0.98-1.52, p = 0.07). According to subgroup analysis, we also did not find a significant association between the hOGG1 Ser326Cys polymorphism and BC risk in Asians and Caucasians considered separately. Conclusions: The current meta-analysis suggests that the hOGG1 Ser326Cys polymorphism is not significantly associated with BC risk.

http://journal.waocp.org/article_43099_deace500bc55d101be4dff8e1a9170e0.pdf

Lack of any Association between the Hogg1 Ser326Cys Polymorphism and Breast Cancer Risk: a Systematic Review And Meta-Analysis Of 18 Studies

BACKGROUND 8-oxoG, a common DNA lesion resulting from reactive oxygen species (ROS), has been shown to be associated with cancer initiation. hOGG1 DNA glycosylase is the primary enzyme responsible for excision of 8-oxoG through base excision repair (BER). Integrins are members of a family of cell surface receptors that mediate the cell-cell and extracellular matrix (ECM) interactions. Integrins are involved in almost every aspect of carcinogenesis, from cell differentiation, cell proliferation, metastasis to angiogenesis. Loss of ITGA2 expression was associated with enhanced tumor intravasation and metastasis of breast and colon cancer. XPD gene encodes DNA helicase enzyme that is involved in nucleotide excision repair (NER). It is shown in previous research that XPD homozygous wildtype Lys/Lys genotype was associated with higher odds of NPC. METHODS We conducted a 1 to N case-control study involving 300 nasopharyngeal carcinoma (NPC) cases and 533 controls matched by age, gender and ethnicity to investigate the effect of hOGG1 Ser326Cys, ITGA2 C807T and XPD Lys751Gln polymorphisms on NPC risk. Linkage disequilibrium and haplotype analysis were conducted to explore the association of allele combinations with NPC risk. Restriction fragment length polymorphism (RFLP-PCR) was used for DNA genotyping. RESULTS No significant association was observed between hOGG1 Ser326Cys and ITGA2 C807T polymorphisms with NPC risk after adjustment for age, gender, ethnicity, cigarette smoking, alcohol and salted fish consumption. Lys/Lys genotype of XPD Lys751Gln polymorphism was associated with increased NPC risk (OR = 1.60, 95% CI = 1.06-2.43). Subjects with history of smoking (OR = 1.81, 95% CI = 1.26-2.60), and salted fish consumption before age of 10 (OR = 1.77, 95% CI = 1.30-2.42) were observed to have increased odds of NPC. The odds of developing NPC of CGC haplotype was significantly higher compared to reference AGC haplotype (OR = 2.20, 95% CI = 1.06-4.58). CONCLUSION The allele combination of CGC from hOGG1, ITGA2 and XPD polymorphisms was significantly associated with increased odds of NPC.

/pdf/haplotype-cgc-from-xpd-hogg1-and-itga2-polymorphisms-59qf1pc1vi.pdf

Haplotype CGC from XPD, hOGG1 and ITGA2 polymorphisms increases the risk of nasopharyngeal carcinoma in Malaysia.

This study has two aims: [1] to evaluate the association between hOGG1 genotypic polymorphism and endometriosis risk, and [2] to investigate the joint effects of hOGG1 genotype and smoking habit on endometriosis susceptibility in Taiwan. For this purpose, the well-known polymorphic variants of hOGG1, codon 326, was genotyped and analyzed of its association with the risk of endometriosis. In total, 153 patients with endometriosis and 636 non-endometriosis healthy controls were recruited and genotyped. The methodology for genotyping is polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Pearson's Chi-square test was performed to compare the distributions of the genotypes between case and control groups. The results showed that the hOGG1 codon 326 genotypes were not differently distributed between the endometriosis and non-endometriosis control groups in both genotypic (P = 0.6212) and allelic (P = 0.4006) frequency analysis. We have further analyzed the genotypic-smoking joint effects on endometriosis risk and found an obvious interaction between hOGG1 codon 326 genotypes and smoking status. The hOGG1 codon 326 genotypes were increased in endometriosis risk only in the smoker groups (P = 0.0061), but not in the non-chewer group (P = 0.0648). Our results provide the evidence that the hOGG1 codon 326 genotype may have a joint effect with smoking on the development of endometriosis.

The joint effect of hOGG1 genotype and smoking habit on endometriosis in Taiwan.

// Jiafei Lu 1, 2, * , Yongmei Yin 3, * , Mulong Du 1, 2, * , Gaoxiang Ma 1, 2 , Yuqiu Ge 1, 2 , Qiang Zhang 1, 2 , Haiyan Chu 1, 2 , Na Tong 1, 2 , Meilin Wang 1, 2 , Jinrong Qiu 3, 4 , Zhengdong Zhang 1, 2 1 Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China 2 Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China 3 Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China 4 Department of Biological-Therapy, Eastern Hepatobiliary Surgery Hospital Affiliated to Second Military Medical University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Zhengdong Zhang, email: drzdzhang@gmail.com Jinrong Qiu, email: jrqiu@njmu.edu.cn Keywords: polymorphism, hOGG1 , gastric cancer, susceptibility Received: March 22, 2016     Accepted: August 24, 2016     Published: September 01, 2016 ABSTRACT Human 8-oxoguanine DNA glycosylase ( hOGG1 ) is known to play an important role in the prevention of carcinogenesis, including gastric cancer (GC). We performed a case-control study to investigate whether single nucleotide polymorphisms (SNPs) of hOGG1 are associated with GC risk in a Chinese population. Two potential functional tagSNPs (rs159153 and rs1052133) and a previously reported risk SNP (rs125701) were genotyped in 1,275 GC patients and 1,436 controls. We found that SNP rs125701 G > A was significantly associated with the increased GC risk [adjusted odds ratio (OR) = 1.38, 95% confidence interval (CI) = 1.05-1.79 in additive model]. Besides, the functional studies demonstrated that the minor A allele of rs125701 significantly reduced the transcriptional activity of hOGG1 promoter and enhanced the methylation level of CpG site of cg15357639. In conclusion, our results suggested that the SNP rs125701 in hOGG1 promoter was associated with the elevated GC risk, which could act as a new potential biomarker for GC susceptibility. Further functional verification of rs125701 in GC pathogenesis is warranted.

/pdf/the-association-analysis-of-hogg1-genetic-variants-and-10sp9r7bdi.pdf

The association analysis of hOGG1 genetic variants and gastric cancer risk in a Chinese population

BACKGROUND The functional Ser326Cys polymorphism in the human 8-oxoguanine DNA glycosylase (hOGG1) gene has been implicated in gastric cancer risk. However, the published findings are inconsistent. We therefore carried out a meta-analysis to investigate this relationship. METHODS Nine published case-control studies, including 1180 gastric cancer cases and 2444 controls, were identified. Odds ratios and 95% confidence intervals were used to assess the strength of the association. RESULTS Overall, the hOGG1 Ser326Cys polymorphism was significantly associated with an increased risk of gastric cancer in a recessive model (Cys/Cys vs. Ser/Cys+Ser/Ser: odds ratio=1.31, 95% confidence interval: 1.03-1.67). In the stratified analysis, a significant association was also observed among Asian populations and hospital-based controls. However, when stratified by smoking status of gastric cancer patients, no statistically significant result was found. CONCLUSION Taken together, the results suggest that the hOGG1 Ser326Cys polymorphism may contribute to susceptibility to gastric cancer.

The functional Ser326Cys polymorphism in hOGG1 is associated with gastric cancer risk: evidence from 1180 cases and 2444 controls.

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The functional Ser326Cys polymorphism in hOGG1 is associated with gastric cancer risk: evidence from 1180 cases and 2444 controls.