Gene Summary

Gene:OGG1; 8-oxoguanine DNA glycosylase
Aliases: HMMH, MUTM, OGH1, HOGG1
Summary:This gene encodes the enzyme responsible for the excision of 8-oxoguanine, a mutagenic base byproduct which occurs as a result of exposure to reactive oxygen. The action of this enzyme includes lyase activity for chain cleavage. Alternative splicing of the C-terminal region of this gene classifies splice variants into two major groups, type 1 and type 2, depending on the last exon of the sequence. Type 1 alternative splice variants end with exon 7 and type 2 end with exon 8. All variants share the N-terminal region in common, which contains a mitochondrial targeting signal that is essential for mitochondrial localization. Many alternative splice variants for this gene have been described, but the full-length nature for every variant has not been determined. [provided by RefSeq, Aug 2008]
Databases:OMIM, VEGA, HGNC, Ensembl, GeneCard, Gene
Protein:N-glycosylase/DNA lyase
Source:NCBIAccessed: 25 June, 2015


What does this gene/protein do?
Show (28)

Cancer Overview

Research Indicators

Publications Per Year (1990-2015)
Graph generated 25 June 2015 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • Odds Ratio
  • Substrate Specificity
  • beta Catenin
  • Genotype
  • Tumor Markers
  • Genetic Association Studies
  • Lung Cancer
  • DNA Glycosylases
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • Saccharomyces cerevisiae
  • DNA-Formamidopyrimidine Glycosylase
  • Breast Cancer
  • Messenger RNA
  • DNA Damage
  • ras Proteins
  • N-Glycosyl Hydrolases
  • Squamous Cell Carcinoma
  • Oxidation-Reduction
  • Species Specificity
  • Adenocarcinoma
  • Polymorphism
  • Colorectal Cancer
  • DNA-Binding Proteins
  • Case-Control Studies
  • Head and Neck Cancers
  • DNA Repair Enzymes
  • Mutation
  • Risk Factors
  • Phosphoric Monoester Hydrolases
  • Genetic Predisposition
  • Chromosome 3
  • Vitamins
  • Xeroderma Pigmentosum
  • Guanine
  • Alleles
  • Uracil-DNA Glycosidase
  • Single-Stranded Conformational Polymorphism
  • Reactive Oxygen Species
  • DNA Repair
  • Deoxyguanosine
  • Prostate Cancer
Tag cloud generated 25 June, 2015 using data from PubMed, MeSH and CancerIndex

Specific Cancers (5)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: OGG1 (cancer-related)

Goričar K, Erčulj N, Faganel Kotnik B, et al.
The association of folate pathway and DNA repair polymorphisms with susceptibility to childhood acute lymphoblastic leukemia.
Gene. 2015; 562(2):203-9 [PubMed] Related Publications
Genetic factors may play an important role in susceptibility to childhood acute lymphoblastic leukemia (ALL). The aim of our study was to evaluate the associations of genetic polymorphisms in folate pathway and DNA repair genes with susceptibility to ALL. In total, 121 children with ALL and 184 unrelated healthy controls of Slovenian origin were genotyped for 14 polymorphisms in seven genes of folate pathway, base excision repair and homologous recombination repair (TYMS, MTHFR, OGG1, XRCC1, NBN, RAD51, and XRCC3). In addition, the exon 6 of NBN was screened for the presence of mutations using denaturing high performance liquid chromatography. Twelve polymorphisms were in Hardy-Weinberg equilibrium in controls and their genotype frequencies were in agreement with those reported in other Caucasian populations. Among the investigated polymorphisms and mutations, NBN Glu185Gln significantly decreased susceptibility to B-cell ALL (p=0.037), while TYMS 3R allele decreased susceptibility to T-cell ALL (p=0.011). Moreover, significantly decreased susceptibility to ALL was observed for MTHFR TA (p=0.030) and RAD51 GTT haplotypes (p=0.016). Susceptibility to ALL increased with the increasing number of risk alleles (ptrend=0.007). We also observed significant influence of hOGG-RAD51 and NBN-RAD51 interactions on susceptibility to ALL. Our results suggest that combination of several polymorphisms in DNA repair and folate pathways may significantly affect susceptibility to childhood ALL.

Songserm N, Promthet S, Pientong C, et al.
Gene-environment interaction involved in cholangiocarcinoma in the Thai population: polymorphisms of DNA repair genes, smoking and use of alcohol.
BMJ Open. 2014; 4(10):e005447 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: Cholangiocarcinoma (CCA) is the most common malignancy in a Northeast Thai population. Smoking and alcohol drinking are associated with the production of free radical intermediates, which can cause several types of DNA lesions. Reduced repair of these DNA lesions would constitute an important risk factor for cancer development. We therefore examined whether polymorphisms in DNA base-excision repair (BER) genes, XRCC1 G399A and OGG1 C326G, were associated with CCA risk and whether they modified the effect of smoking and alcohol drinking in the Thai population.
DESIGN: A nested case-control study within the cohort study was conducted: 219 participants with primary CCA were each matched with two non-cancer controls from the same cohort on sex, age at recruitment and the presence/absence of Opisthorchis viverrini eggs in stools. Smoking and alcohol consumption were assessed on recruitment. Polymorphisms in BER genes were analysed using a PCR with high-resolution melting analysis. The associations were assessed using conditional logistic regression.
RESULTS: Our results suggest that, in the Thai population, polymorphisms in XRCC1 and OGG1 genes, particularly in combination, are associated with increased susceptibility to CCA, and that their role as modifiers of the effect of smoking and alcohol consumption influences the risk of CCA.
CONCLUSIONS: Better ways of reducing habitual smoking and alcohol consumption, targeted towards subgroups which are genetically susceptible, are recommended. CCA is a multifactorial disease, and a comprehensive approach is needed for its effective prevention. This approach would also have the additional advantage of reducing the onset of other cancers.

Wang Y, Gao X, Wei F, et al.
The hOGG1 Ser326Cys polymorphism contributes to digestive system cancer susceptibility: evidence from 48 case-control studies.
Tumour Biol. 2015; 36(2):1029-38 [PubMed] Related Publications
The Ser326Cys polymorphism in the human 8-oxogunaine DNA glycosylase (hOGG1) gene had been implicated in cancer susceptibility. Studies investigating the associations between the Ser326Cys polymorphism and digestion cancer susceptibility showed conflicting results. Therefore, a meta-analysis was performed to derive a more precise estimation of the relationship. We conducted a meta-analysis of 48 studies that included 12,073 cancer cases and 19,557 case-free controls. We assessed the strength of the association using odds ratios (ORs) with 95% confidence intervals (CIs). In our analysis, the hOGG1 Ser326Cys polymorphism was significantly associated with the risk of digestive system cancers (Cys/Cys vs. Ser/Ser: OR = 1.17, 95% CI = 1.00-1.35, P < 0.001; Cys/Cys vs. Cys/Ser + Ser/Ser: OR = 1.14, 95% CI = 1.00-1.29, P < 0.001). In subgroup analyses by cancer types, we found that the hOGG1 Ser326Cys polymorphism may increase hepatocellular cancer and colorectal cancer risks, but decrease the risk of oral cancer. These findings supported that hOGG1 Ser326Cys polymorphism may contribute to the susceptibility of digestive cancers.

Gerstenberger JP, Bauer SR, Van Blarigan EL, et al.
Selenoprotein and antioxidant genes and the risk of high-grade prostate cancer and prostate cancer recurrence.
Prostate. 2015; 75(1):60-9 [PubMed] Article available free on PMC after 01/01/2016 Related Publications
BACKGROUND: Observational studies suggest an inverse association between selenium and risk of prostate cancer. However, randomized controlled trials of selenium supplementation have reported conflicting results. Thus, we examined plasma selenium and selenium-related genes in relation to risk of high-grade prostate cancer and prostate cancer recurrence among men initially diagnosed with non-metastatic disease.
METHODS: We measured plasma selenium and genotyped 73 single nucleotide polymorphisms in TXNRD1, TXNRD2, GPX1, GPX3, GPX4, SEP15, SEPP1, SELENBP1, OGG1, and CAT among 568 men with non-metastatic prostate cancer who underwent radical prostatectomy. We examined associations between plasma selenium, genotypes, and risk of high-grade prostate cancer (Gleason grade ≥8 or 7 with primary score ≥4; n = 111) using logistic regression, and risk of prostate cancer recurrence (61 events; 3.8 y median follow-up) using Cox proportional hazards regression.
RESULTS: Plasma selenium was not associated with risk of high-grade prostate cancer or prostate cancer recurrence. Less common alleles of rs11913319 in TXNRD2 and rs125701 in OGG1 were associated with an increased risk of high-grade prostate cancer. We observed associations between the risk of prostate cancer recurrence and multiple SNPs in TXNRD1, TXNRD2, GPX3, and SEP15. These associations were no longer statistically significant after adjustment for multiple comparisons.
CONCLUSIONS: Among men with non-metastatic prostate cancer, there is suggestive evidence that genetic variation in selenoproteins and related antioxidant enzymes may be associated with risk of high-grade disease at diagnosis and prostate cancer recurrence.

Yong KJ, Milenic DE, Baidoo KE, Brechbiel MW
Impact of α-targeted radiation therapy on gene expression in a pre-clinical model for disseminated peritoneal disease when combined with paclitaxel.
PLoS One. 2014; 9(9):e108511 [PubMed] Article available free on PMC after 01/01/2016 Related Publications
To better understand the molecular basis of the enhanced cell killing effected by the combined modality of paclitaxel and ²¹²Pb-trastuzumab (Pac/²¹²Pb-trastuzumab), gene expression in LS-174T i.p. xenografts was investigated 24 h after treatment. Employing a real time quantitative PCR array (qRT-PCR array), 84 DNA damage response genes were quantified. Differentially expressed genes following therapy with Pac/²¹²Pb-trastuzumab included those involved in apoptosis (BRCA1, CIDEA, GADD45α, GADD45γ, GML, IP6K3, PCBP4, PPP1R15A, RAD21, and p73), cell cycle (BRCA1, CHK1, CHK2, GADD45α, GML, GTSE1, NBN, PCBP4, PPP1R15A, RAD9A, and SESN1), and damaged DNA repair (ATRX, BTG2, EXO1, FEN1, IGHMBP2, OGG1, MSH2, MUTYH, NBN, PRKDC, RAD21, and p73). This report demonstrates that the increased stressful growth arrest conditions induced by the Pac/²¹²Pb-trastuzumab treatment suppresses cell proliferation through the regulation of genes which are involved in apoptosis and damaged DNA repair including single and double strand DNA breaks. Furthermore, the study demonstrates that ²¹²Pb-trastuzumab potentiation of cell killing efficacy results from the perturbation of genes related to the mitotic spindle checkpoint and BASC (BRCA1-associated genome surveillance complex), suggesting cross-talk between DNA damage repair and the spindle damage response.

Santos JC, Funck A, Silva-Fernandes IJ, et al.
Effect of APE1 T2197G (Asp148Glu) polymorphism on APE1, XRCC1, PARP1 and OGG1 expression in patients with colorectal cancer.
Int J Mol Sci. 2014; 15(10):17333-43 [PubMed] Article available free on PMC after 01/01/2016 Related Publications
It has been hypothesized that genetic variation in base excision repair (BER) might modify colorectal adenoma risk. Thus, we evaluated the influence of APE1 T2197G (Asp148Glu) polymorphism on APE1, XRCC1, PARP1 and OGG1 expression in normal and tumor samples from patients with colorectal cancer. The results indicate a downregulation of OGG1 and an upregulation of XRCC1 expression in tumor tissue. Regarding the anatomical location of APE1, OGG1 and PARP-1, a decrease in gene expression was observed among patients with cancer in the rectum. In patients with or without some degree of tumor invasion, a significant downregulation in OGG1 was observed in tumor tissue. Interestingly, when taking into account the tumor stage, patients with more advanced grades (III and IV) showed a significant repression for APE1, OGG1 and PARP-1. XRCC1 expression levels were significantly enhanced in tumor samples and were correlated with all clinical and histopathological data. Concerning the polymorphism T2197G, GG genotype carriers exhibited a significantly reduced expression of genes of the BER repair system (APE1, XRCC1 and PARP1). In summary, our data show that patients with colorectal cancer present expression changes in several BER genes, suggesting a role for APE1, XRCC1, PARP1 and OGG1 and APE1 polymorphism in colorectal carcinogenesis.

Zhang M, Mo R
Association of hOGG1 Ser326Cys polymorphism with colorectal cancer risk: an updated meta-analysis including 5235 cases and 8438 controls.
Tumour Biol. 2014; 35(12):12627-33 [PubMed] Related Publications
It has been suggested that hOGG1 Ser326Cys polymorphism may be a risk factor for colorectal cancer. Published data on its association with colorectal cancer generated contradictory results; thus, we performed an updated meta-analysis of eligible published studies to estimate the effect of hOGG1 Ser326Cys polymorphism on colorectal cancer susceptibility. We reviewed many abstracts and finally included 18 eligible case-control studies comprising 5235 cases and 8438 controls. We pooled data with a fixed or random-effect model. Subgroup analysis by ethnicity was also performed. The overall data indicated a significant association of hOGG1 Ser326Cys polymorphism on colorectal cancer risk (allele model OR = 1.14, 95 %CI 1.02-1.27; homozygote model OR = 1.32, 95 %CI 0.92-1.92; recessive model OR = 1.12, 95 %CI 1.00-1.26; dominant model OR = 1.15, 95 %CI 1.00-1.32). Furthermore, in the subgroup analysis by ethnicity, increased cancer risk was observed among Caucasians under the allele, heterogeneity, recessive, and dominant models (allele model OR = 1.23, 95 %CI = 1.05-1.44; homozygote model OR = 1.49, 95%CI 1.05-2.12; recessive model OR = 1.40, 95 %CI 1.16-1.69; dominant model OR = 1.21, 95 %CI = 1.12-1.45). In summary, the present meta-analysis suggested that hOGG1 Ser326Cys polymorphism might modify the susceptibility to colorectal cancer among the total population, especially among Caucasians.

Ramaniuk VP, Nikitchenko NV, Savina NV, et al.
Polymorphism of DNA repair genes OGG1, XRCC1, XPD and ERCC6 in bladder cancer in Belarus.
Biomarkers. 2014; 19(6):509-16 [PubMed] Related Publications
CONTEXT: The study of DNA base and nucleotide excision repair gene polymorphisms in bladder cancer seems to have a predictive value because of the evident relationship between the DNA damage response induced by environmental mutagens and cancer predisposition.
OBJECTIVE: The objective was to determine OGG1 Ser326Cys, XRCC1 Arg399Gln, XPD Asp312Asn, and ERCC6 Met1097Val polymorphisms in bladder cancer patients as compared to controls.
METHODS: Both groups were predominantly represented by Belarusians and Eastern Slavs. DNA samples from 336 patients and 370 controls were genotyped using a PCR-RFLP method.
RESULTS: The genotype distributions were in agreement with the Hardy-Weinberg equilibrium. The minor allele frequencies in the control population were in the range of those in Caucasians in contrast to Asians. The OGG1 326 Ser/Cys and XPD 312 Asp/Asn heterozygous genotypes were inversely associated with cancer risk (OR [95% CI] = 0.69 [0.50-0.95] and 1.35 [1.0-1.82], respectively). The contrasting effects of these genotypes were potentiated due to their interactions with smoking habit or age.
CONCLUSIONS: Among four DNA repair gene polymorphisms, the OGG1 326 Ser/Cys and XPD 312 Asp/Asn heterozygous genotypes might be recognized as potential genetic markers modifying susceptibility to bladder cancer in Belarus.

Zhang SH, Wang LA, Li Z, et al.
APE1 polymorphisms are associated with colorectal cancer susceptibility in Chinese Hans.
World J Gastroenterol. 2014; 20(26):8700-8 [PubMed] Article available free on PMC after 01/01/2016 Related Publications
AIM: To study the association between four base excision repair gene polymorphisms and colorectal cancer risk in a Chinese population.
METHODS: Two hundred forty-seven colorectal cancer (CRC) patients and three hundred cancer-free controls were enrolled in this study. Four polymorphisms (OGG1 Ser326Cys, APE1 Asp148Glu, -141T/G in the promoter region, and XRCC1 Arg399Gln) in components of the base excision repair pathway were determined in patient blood samples using polymerase chain reaction with confronting two-pair primers. The baseline information included age, gender, family history of cancer, and three behavioral factors [smoking status, alcohol consumption, and body mass index (BMI)]. χ(2) tests were used to assess the Hardy-Weinberg equilibrium, the distributions of baseline characteristics, and the four gene polymorphisms between the cases and controls. Multivariate logistic regression analyses were conducted to analyze the correlations between the four polymorphisms and CRC risk, adjusted by the baseline characteristics. Likelihood ratio tests were performed to analyze the gene-behavior interactions of smoking status, alcohol consumption, and BMI on polymorphisms and CRC susceptibility.
RESULTS: The APE1 148 Glu/Glu genotype was significantly associated with an increased risk of colorectal cancer (OR = 2.411, 95%CI: 1.497-3.886, P < 0.001 relative to Asp/Asp genotype). There were no associations between OGG1, XRCC1, or APE1 promoter polymorphisms and CRC risk. A multivariate analysis including three behavioral factors showed that the APE1 148 Glu/Glu genotype was associated with an increased risk for CRC among both smokers and non-smokers, non-drinkers and individuals with a BMI ≥ 25 kg/m(2) (ORs = 2.356, 3.299, 2.654, and 2.581, respectively). The XRCC1 399 Arg/Gln genotype was associated with a decreased risk of CRC among smokers and drinkers (OR = 0.289, 95%CI: 0.152-0.548, P < 0.001, and OR = 0.327, 95%CI: 0.158-0.673, P < 0.05, respectively). The APE1 promoter polymorphism -141 T/G genotype was associated with a reduced risk of colorectal cancer among subjects with a BMI < 25 kg/m(2) (OR = 0.214, 95%CI: 0.069-0.660, P < 0.05 relative to T/T genotype). There were significant gene-behavior interactions between smoking status and XRCC1 Arg399Gln, as well as BMI and APE1 -141T/G polymorphism (all P < 0.05).
CONCLUSION: APE1 Asp148Glu is associated with increased CRC risk and smoking alters the association between XRCC1 Arg399Gln and CRC risk in the Chinese Han population.

Marques CR, Da Silva TM, De Albuquerque DM, et al.
NAT2, XRCC1 and hOGG1 polymorphisms, cigarette smoking, alcohol consumption and risk of upper aerodigestive tract cancer.
Anticancer Res. 2014; 34(6):3217-24 [PubMed] Related Publications
AIM: To evaluate associations between polymorphisms of the N-acetyltransferase 2 (NAT2), human 8-oxoguanine glycosylase 1 (hOGG1) and X-ray repair cross-complementing protein 1 (XRCC1) genes and risk of upper aerodigestive tract (UADT) cancer.
PATIENTS AND METHODS: A case-control study involving 117 cases and 224 controls was undertaken. The NAT2 gene polymorphisms were genotyped by automated sequencing and XRCC1 Arg399Gln and hOGG1 Ser326Cys polymorphisms were determined by Polymerase Chain Reaction followed by Restriction Fragment Length Polymorphism (PCR-RFLP) methods.
RESULTS: Slow metabolization phenotype was significantly associated as a risk factor for the development of UADT cancer (p=0.038). Furthermore, haplotype of slow metabolization was also associated with UADT cancer (p=0.014). The hOGG1 Ser326Cys polymorphism (CG or GG vs. CC genotypes) was shown as a protective factor against UADT cancer in moderate smokers (p=0.031). The XRCC1 Arg399Gln polymorphism (GA or AA vs. GG genotypes), in turn, was a protective factor against UADT cancer only among never-drinkers (p=0.048).
CONCLUSION: Interactions involving NAT2, XRCC1 Arg399Gln and hOGG1 Ser326Cys polymorphisms may modulate the risk of UADT cancer in this population.

Singh B, Shoulson R, Chatterjee A, et al.
Resveratrol inhibits estrogen-induced breast carcinogenesis through induction of NRF2-mediated protective pathways.
Carcinogenesis. 2014; 35(8):1872-80 [PubMed] Article available free on PMC after 01/08/2015 Related Publications
The importance of estrogens in the etiology of breast cancer is widely recognized. Estrogen-induced oxidative stress has been implicated in this carcinogenic process. Resveratrol (Res), a natural antioxidant phytoestrogen has chemopreventive effects against a variety of illnesses including cancer. The objective of the present study was to characterize the mechanism(s) of Res-mediated protection against estrogen-induced breast carcinogenesis. Female August Copenhagen Irish rats were treated with 17β-estradiol (E2), Res and Res + E2 for 8 months. Cotreatment of rats with Res and E2 inhibited E2-mediated proliferative changes in mammary tissues and significantly increased tumor latency and reduced E2-induced breast tumor development. Resveratrol treatment alone or in combination with E2 significantly upregulated expression of nuclear factor erythroid 2-related factor 2 (NRF2) in mammary tissues. Expression of NRF2-regulated antioxidant genes NQO1, SOD3 and OGG1 that are involved in protection against oxidative DNA damage was increased in Res- and Res + E2-treated mammary tissues. Resveratrol also prevented E2-mediated inhibition of detoxification genes AOX1 and FMO1. Inhibition of E2-mediated alterations in NRF2 promoter methylation and expression of NRF2 targeting miR-93 after Res treatment indicated Res-mediated epigenetic regulation of NRF2 during E2-induced breast carcinogenesis. Resveratrol treatment also induced apoptosis and inhibited E2-mediated increase in DNA damage in mammary tissues. Increased apoptosis and decreased DNA damage, cell migration, colony and mammosphere formation in Res- and Res + E2-treated MCF-10A cells suggested a protective role of Res against E2-induced mammary carcinogenesis. Small-interfering RNA-mediated silencing of NRF2 inhibited Res-mediated preventive effects on the colony and mammosphere formation. Taken together, these results suggest that Res inhibits E2-induced breast carcinogenesis via induction of NRF2-mediated protective pathways.

Peng Q, Lu Y, Lao X, et al.
Association between OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and breast cancer risk: a meta-analysis.
Diagn Pathol. 2014; 9:108 [PubMed] Article available free on PMC after 01/08/2015 Related Publications
BACKGROUND: The base excision repair (BER) pathway removes DNA damage caused by ionizing radiation, reactive oxidative species and methylating agents. OGG1 and APE1 are two important genes in the BER pathway. Many epidemiological studies have evaluated the association between polymorphisms in the two BER genes (OGG1 Ser326Cys and APE1 Asp148Glu) and breast cancer risk. However, the results are inconsistent.
METHODS: We searched the electronic databases including PubMed, Embase and Cochrane library for all eligible studies for the period up to February 2014. Data were extracted by two independent authors and pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to assess the strength of the association.
RESULTS: A total of 17 studies including 9,040 cases and 10,042 controls were available for OGG1 Ser326Cys polymorphism and 7 studies containing 2,979 cases and 3,111 controls were included for APE1 Asp148Glu polymorphism. With respect to OGG1 Ser326Cys polymorphism, we did not find a significant association with breast cancer risk when all eligible studies were pooled into the meta-analysis. However, in subgroup analyses by ethnicity and menopausal status, statistical significant increased breast cancer risk was found in Asian populations (Cys/Cys vs. Ser/Ser: OR=1.157, 95% CI 1.013-1.321, P=0.011; Cys/Cys vs. Ser/Cys+Ser/Ser: OR=1.113, 95% CI 1.009-1.227, P=0.014) and postmenopausal patients (Cys/Cys vs. Ser/Cys+Ser/Ser: OR=1.162, 95% CI 1.003-1.346, P=0.024). In subgroup analysis according to quality score, source of control, and HWE in controls, no any significant association was detected. With respect to APE1 Asp148Glu polymorphism, no significant association with breast cancer risk was demonstrated in the overall and stratified analyses.
CONCLUSIONS: The present meta-analysis suggests that the OGG1 Ser326Cys polymorphism may be a risk factor for breast cancer in Asians and postmenopausal patients. Further large and well-designed studies are needed to confirm this association.
VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1156934297124915.

Shinmura K, Goto M, Tao H, et al.
Impaired 8-hydroxyguanine repair activity of MUTYH variant p.Arg109Trp found in a Japanese patient with early-onset colorectal cancer.
Oxid Med Cell Longev. 2014; 2014:617351 [PubMed] Article available free on PMC after 01/08/2015 Related Publications
PURPOSE: The biallelic inactivation of the 8-hydroxyguanine repair gene MUTYH leads to MUTYH-associated polyposis (MAP), which is characterized by colorectal multiple polyps and carcinoma(s). However, only limited information regarding MAP in the Japanese population is presently available. Since early-onset colorectal cancer (CRC) is a characteristic of MAP and might be caused by the inactivation of another 8-hydroxyguanine repair gene, OGG1, we investigated whether germline MUTYH and OGG1 mutations are involved in early-onset CRC in Japanese patients.
METHODS: Thirty-four Japanese patients with early-onset CRC were examined for germline MUTYH and OGG1 mutations using sequencing.
RESULTS: Biallelic pathogenic mutations were not found in any of the patients; however, a heterozygous p.Arg19∗  MUTYH variant and a heterozygous p.Arg109Trp MUTYH variant were detected in one patient each. The p.Arg19∗ and p.Arg109Trp corresponded to p.Arg5∗ and p.Arg81Trp, respectively, in the type 2 nuclear-form protein. The defective DNA repair activity of p.Arg5∗ is apparent, while that of p.Arg81Trp has been demonstrated using DNA cleavage and supF forward mutation assays.
CONCLUSION: These results suggest that biallelic MUTYH or OGG1 pathogenic mutations are rare in Japanese patients with early-onset CRC; however, the p.Arg19∗ and p.Arg109Trp MUTYH variants are associated with functional impairments.

Kim HN, Kim NY, Yu L, et al.
Polymorphisms in DNA repair genes and MDR1 and the risk for non-Hodgkin lymphoma.
Int J Mol Sci. 2014; 15(4):6703-16 [PubMed] Article available free on PMC after 01/08/2015 Related Publications
The damage caused by oxidative stress and exposure to cigarette smoke and alcohol necessitate DNA damage repair and transport by multidrug resistance-1 (MDR1). To explore the association between polymorphisms in these genes and non-Hodgkin lymphoma risk, we analyzed 15 polymorphisms of 12 genes in a population-based study in Korea (694 cases and 1700 controls). Four genotypes of DNA repair pathway genes (XRCC1 399 GA, OGG1 326 GG, BRCA1 871 TT, and WRN 787 TT) were associated with a decreased risk for NHL [odds ratio (OR)XRCC1 GA=0.80, p=0.02; OROGG1 GG=0.70, p=0.008; ORBRCA1 TT=0.71, p=0.048; ORWRN TT=0.68, p=0.01]. Conversely, the MGMT 115 CT genotype was associated with an increased risk for NHL (OR=1.25, p=0.04). In the MDR1 gene, the 1236 CC genotype was associated with a decreased risk for NHL (OR=0.74, p=0.04), and the 3435 CT and TT genotypes were associated with an increased risk (OR3435CT=1.50, p<0.0001; OR3435TT=1.43, p=0.02). These results suggest that polymorphisms in the DNA repair genes XRCC1, OGG1, BRCA1, WRN1, and MGMT and in the MDR1 gene may affect the risk for NHL in Korean patients.

Peng Y, Li Z, Zhang S, et al.
Association of DNA base excision repair genes (OGG1, APE1 and XRCC1) polymorphisms with outcome to platinum-based chemotherapy in advanced nonsmall-cell lung cancer patients.
Int J Cancer. 2014; 135(11):2687-96 [PubMed] Related Publications
Polymorphism of DNA base excision repair (BER) genes affects DNA repair capacity and may alter sensitivity to platinum-based chemotherapy regimens. This study investigated polymorphisms of OGG1 Ser326Cys, APE1 Asp148Glu APE1-141T/G and XRCC1 Arg399Gln for association with clinical outcome in 235 advanced inoperable nonsmall-cell lung cancer (NSCLC) patients after treatment with platinum-based chemotherapy. The multivariate analysis showed that OGG1 326 GC was associated with poor PFS [hazard ratio (HR) 1.730, p = 0.005], while XRCC1 399 GA, or GA+AA, was associated with poor OS in short-term period (HR 1.718, p = 0.003; HR 1.691, p = 0.003, respectively). Patients with OGG1 326/XRCC1 399 variant alleles had a higher risk to die early in short-term period (HR 1.929, p < 0.001). Furthermore, patients with XRCC1 399 variant allele (GA+AA) had higher risk of hematologic toxicity (p = 0.009), whereas patients carrying the OGG1 326 variant (GG), or the APE1-141 GG variant, had reduced risk of gastrointestinal toxicity (p = 0.015 and p = 0.023, respectively). The data from the current study provide evidence that OGG1 Ser326Cys, XRCC1 Arg399Gln, APE1 Asp148Glu, and APE1-141T/G polymorphisms may be useful in predicting clinical outcomes in patients with advanced inoperable NSCLC that will undergo platinum-based chemotherapy.

Osorio A, Milne RL, Kuchenbaecker K, et al.
DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers.
PLoS Genet. 2014; 10(4):e1004256 [PubMed] Article available free on PMC after 01/08/2015 Related Publications
Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 × 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 × 10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.

Mahjabeen I, Ali K, Zhou X, Kayani MA
Deregulation of base excision repair gene expression and enhanced proliferation in head and neck squamous cell carcinoma.
Tumour Biol. 2014; 35(6):5971-83 [PubMed] Related Publications
Defects in the DNA damage repair pathway contribute to cancer. The major pathway for oxidative DNA damage repair is base excision repair (BER). Although BER pathway genes (OGG1, APEX1 and XRCC1) have been investigated in a number of cancers, our knowledge on the prognostic significance of these genes and their role in head and neck squamous cell carcinoma is limited. Protein levels of OGG1, APEX1 and XRCC1 and a proliferation marker, Ki-67, were examined by immunohistochemical analysis, in a cohort of 50 HNSCC patients. Significant downregulation of OGG1 (p<0.04) and XRCC1 (p<0.05) was observed in poorly differentiated HNSCC compared to mod-well-differentiated cases. Significant upregulation of APEX1 (p<0.05) and Ki-67 (p<0.05) was observed in poorly differentiated HNSCC compared to mod-well-differentiated cases. Significant correlation was observed between XRCC1 and OGG1 (r=0.33, p<0.02). Inverse correlations were observed between OGG1 and Ki-67 (r=-0.377, p<0.005), between APEX1 and XRCC1 (r=-0.435, p<0.002) and between OGG1 and APEX1 (r=-0.34, p<0.02) in HNSCC. To confirm our observations, we examined BER pathway genes and a proliferation marker, Ki-67, expression at the mRNA level on 50 head and neck squamous cell carcinoma (HNSCC) and 50 normal control samples by quantitative real-time polymerase chain reaction. Significant downregulation was observed in case of OGG1 (p<0.04) and XRCC1 (p<0.02), while significant upregulation was observed in case of APEX1 (p<0.01) and Ki-67 (p<0.03) in HNSCC tissue samples compared to controls. Our data suggested that deregulation of base excision repair pathway genes, such as OGG1, APEX1 and XRCC1, combined with overexpression of Ki-67, a marker for excessive proliferation, may contribute to progression of HNSCC in Pakistani population.

Ramdzan ZM, Vadnais C, Pal R, et al.
RAS transformation requires CUX1-dependent repair of oxidative DNA damage.
PLoS Biol. 2014; 12(3):e1001807 [PubMed] Article available free on PMC after 01/08/2015 Related Publications
The Cut homeobox 1 (CUX1) gene is a target of loss-of-heterozygosity in many cancers, yet elevated CUX1 expression is frequently observed and is associated with shorter disease-free survival. The dual role of CUX1 in cancer is illustrated by the fact that most cell lines with CUX1 LOH display amplification of the remaining allele, suggesting that decreased CUX1 expression facilitates tumor development while increased CUX1 expression is needed in tumorigenic cells. Indeed, CUX1 was found in a genome-wide RNAi screen to identify synthetic lethal interactions with oncogenic RAS. Here we show that CUX1 functions in base excision repair as an ancillary factor for the 8-oxoG-DNA glycosylase, OGG1. Single cell gel electrophoresis (comet assay) reveals that Cux1⁺/⁻ MEFs are haploinsufficient for the repair of oxidative DNA damage, whereas elevated CUX1 levels accelerate DNA repair. In vitro base excision repair assays with purified components demonstrate that CUX1 directly stimulates OGG1's enzymatic activity. Elevated reactive oxygen species (ROS) levels in cells with sustained RAS pathway activation can cause cellular senescence. We show that elevated expression of either CUX1 or OGG1 prevents RAS-induced senescence in primary cells, and that CUX1 knockdown is synthetic lethal with oncogenic RAS in human cancer cells. Elevated CUX1 expression in a transgenic mouse model enables the emergence of mammary tumors with spontaneous activating Kras mutations. We confirmed cooperation between Kras(G12V) and CUX1 in a lung tumor model. Cancer cells can overcome the antiproliferative effects of excessive DNA damage by inactivating a DNA damage response pathway such as ATM or p53 signaling. Our findings reveal an alternate mechanism to allow sustained proliferation in RAS-transformed cells through increased DNA base excision repair capability. The heightened dependency of RAS-transformed cells on base excision repair may provide a therapeutic window that could be exploited with drugs that specifically target this pathway.

Luo H, Li Z, Qing Y, et al.
Single nucleotide polymorphisms of DNA base-excision repair genes (APE1, OGG1 and XRCC1) associated with breast cancer risk in a Chinese population.
Asian Pac J Cancer Prev. 2014; 15(3):1133-40 [PubMed] Related Publications
Altered DNA repair capacity can result in increased susceptibility to cancer. The base excision repair (BER) pathway effectively removes DNA damage caused by ionizing radiation and reactive oxidative species (ROS). In the current study, we analyzed the possible relation of polymorphisms in BER genes, including 8-oxoguanine DNA glycosylase (OGG1), apurinic/apyrimidinic endonuclease 1 (APE1), and X-ray repair cross-complementing group 1 protein (XRCC1), with breast cancer risk in Chinese Han women. This case-control study examined 194 patients with breast cancer and 245 cancer-free hospitalized control subjects. Single nucleotide polymorphisms (SNPs) of OGG1 (Ser326Cys), XRCC1 (Arg399Gln), and APE1 (Asp148Glu and -141T/G) were genotyped and analyzed for their association with breast cancer risk using multivariate logistic regression models. We found that XRCC1 Arg399Gln was significantly associated with an increased risk of breast cancer. Similarly, the XRCC1 Gln allele was significantly associated with an elevated risk in postmenopausal women and women with a high BMI (≥ 24 kg/m2). The OGG1 Cys allele provided a significant protective effect against developing cancer in women with a low BMI (< 24 kg/m2). When analyzing the combined effects of these alleles on the risk of breast cancer, we found that individuals with ≥ 2 adverse genotypes (XRCC1 399Gln, APE1 148Asp, and OGG1 326Ser) were at a 2.18-fold increased risk of breast cancer (P = 0.027). In conclusion, our data indicate that Chinese women with the 399Gln allele of XRCC1 have an increased risk of breast cancer, and the combined effects of polymorphisms of BER genes may contribute to tumorigenesis.

De Summa S, Pinto R, Pilato B, et al.
Expression of base excision repair key factors and miR17 in familial and sporadic breast cancer.
Cell Death Dis. 2014; 5:e1076 [PubMed] Article available free on PMC after 01/08/2015 Related Publications
Understanding of BRCA1/2 interaction with the base excision repair (BER) pathway could improve therapy based on 'synthetic lethality', whose effectiveness is based on homologous recombination deficiency in cells lacking functional BRCA genes. However, poly (ADP-ribose) polymerase (PARP) inhibitors failed in some patients and for this reason we explored BER key enzyme expression. In this study, the expression of BER enzymes (redox factor 1/apurinic-apyrimidinic endonuclease 1 (REF1/APEX1), NTH endonuclease III-like 1 (NTHL1), 8-oxoguanine DNA glycosylase (OGG1), PARP1) and of the scaffold protein XRCC1 (X-ray repair complementing defective repair in Chinese hamster cells 1) were investigated in familial (BRCA-related and not) and sporadic breast cancer cases. Furthermore, miR17 expression was measured because of its role in the epigenetic regulation of BRCA1. Gene expression was evaluated in BRCA1-mutated cell lines, SUM149PT and SUM1315MO2, and in a BRCA1-proficient triple-negative MDA-MB-231 cell line. A cohort of 27 familial and 16 sporadic breast cancer patients was then examined to confirm results obtained from the cell line model. APEX1/REF1 was found to be upregulated in familial BRCA-wild-type and sporadic cases, indicating this enzyme as a potential therapeutic target. Furthermore, XRCC1 was overexpressed in BRCAX patients; consequently, we suggest to test the effectiveness of inhibitors targeting two different BER components in preclinical studies. XRCC1, which is also involved in the non-homologous end-joining pathway, was found to be downregulated in BRCA2-related patients concurrently with no change in PARP1 expression. Interestingly, no difference in PARP1 and miR17 expression was found in BRCA-related and sporadic breast cancer cases. PARP1 and miR17 could therefore be further investigated as molecular biomarkers of 'BRCAness' phenotype, indicating patients which could really benefit from PARP inhibitor therapies.

Adel Fahmideh M, Schwartzbaum J, Frumento P, Feychting M
Association between DNA repair gene polymorphisms and risk of glioma: a systematic review and meta-analysis.
Neuro Oncol. 2014; 16(6):807-14 [PubMed] Article available free on PMC after 01/08/2015 Related Publications
BACKGROUND: Association studies of germline DNA repair single nucleotide polymorphisms (SNPs) and glioma risk have yielded inconclusive results. We therefore performed a systematic review and meta-analysis of studies investigating this association.
METHODS: We identified 27 eligible studies investigating 105 SNPs in 42 DNA repair genes. Of these, 10 SNPs in 7 genes were analyzed in at least 4 studies and were therefore included in our meta-analysis. The meta-analysis was performed for homozygote comparison, heterozygote comparison, and dominant and recessive models by applying a fixed- or random-effects model. The funnel and forest plots were created using RevMan software.
RESULTS: We found that SNPs rs3212986 (odds ratio [OR] = 1.35 (1.08-1.68), P = .008), rs13181 (OR = 1.18 (1.06-1.31), P = .002), and rs25487 (OR = 1.12 (1.03-1.22), P = .007) in DNA repair genes ERCC1, ERCC2 (XPD), and XRCC1 may increase the risk of glioma, while polymorphisms rs1136410 (OR = 0.78 (0.68-0.89), P = .0004) and rs12917 (OR = 0.84 (0.73-0.96), P = .01) in PARP1(ADPRT) and MGMT are associated with decreased susceptibility to glioma. No evidence of significant associations between ERCC2 rs1799793, OGG1 rs1052133, XRCC1 rs25489, XRCC1 rs1799782, or XRCC3 rs861539 and risk of glioma was observed.
CONCLUSION: This study provides evidence that DNA repair genes ERCC1, ERCC2, and XRCC1 might be low-penetrance glioma-risk genes, while MGMT and PARP1 polymorphisms may confer protection against glioma.

Geng P, Yao J, Zhu Y
hOGG1 Ser326Cys polymorphism and lung cancer susceptibility: a meta-analysis.
Mol Biol Rep. 2014; 41(4):2299-306 [PubMed] Related Publications
The Ser326Cys polymorphism in the human 8-oxogunaine glycosylase (hOGG1) gene with lung cancer susceptibility had been investigated by the approaches of PCR-RFLP, PCR-SSCP and ASA. Due to limited specimen and different approaches the conclusion was drawn toughly. To evaluate this correlation comprehensively, a meta-analysis was performed based on 30 case-control studies, including 10,327 cases and 12,148 controls. The random-effects model was used to estimate the odds ratios and 95 % confidence interval for various contrasts of this polymorphism. The combined results suggested that the hOGG1 Ser326Cys polymorphism was not associated with lung cancer susceptibility in different genetic models. Similarly, in the stratified analyses by ethnicity and source of control, no risk was observed between all the genetic models and lung cancer risk. Our meta-analysis revealed that there was little correlation between the hOGG1 Ser326Cys polymorphism and the risk of lung cancer.

Smolarz B, Makowska M, Samulak D, et al.
Single nucleotide polymorphisms (SNPs) of ERCC2, hOGG1, and XRCC1 DNA repair genes and the risk of triple-negative breast cancer in Polish women.
Tumour Biol. 2014; 35(4):3495-502 [PubMed] Article available free on PMC after 01/08/2015 Related Publications
Triple-negative breast cancer (TNBC) refers to about 15-20% of all breast cancer cases. It is characterized by worse clinical outcome, poor prognosis, and absence of prognostic indicators. Several polymorphisms in the nucleotide excision repair (NER) and base excision repair (BER) gene have been extensively studied in association with various human cancers. The aim of this study was to evaluate the role of the hOGG1-Ser326Cys (rs13181), XRCC1-Arg194Trp (rs1799782), and ERCC2-Lys751Gln (rs13181) gene polymorphisms with clinical parameters and the risk for development of triple-negative breast cancer. Our research included 70 patients with TNBC and 70 healthy controls. Gene polymorphisms were genotyped by the PCR-RFLP (restriction fragment length polymorphism) method. The genotype distributions were contrasted by the chi-square test, and the significance of the polymorphism was assessed by multiple logistic regression producing odds ratios (ORs) and 95% confidence intervals (CIs). In the present work, a relationship was identified between ERCC2-Lys751Gln polymorphism and the incidence of triple-negative breast cancer. An association was observed between triple-negative breast carcinoma occurrence and the presence of Gln/Gln genotype (OR = 5.71 (2.12-5.43), p = 0.0007). A tendency for an increased risk of TNBC was detected with the occurrence of 751Gln allele of ERCC2 polymorphism. No significant associations between Ser326Cys and Arg194Trp genotype and TNBC were observed. We suggest that the Lys751Gln polymorphism of the ERCC2 gene may be risk factors for triple-negative breast cancer development in Polish women.

Fleischer T, Edvardsen H, Solvang HK, et al.
Integrated analysis of high-resolution DNA methylation profiles, gene expression, germline genotypes and clinical end points in breast cancer patients.
Int J Cancer. 2014; 134(11):2615-25 [PubMed] Related Publications
Breast cancer is a heterogeneous disease for which alterations in DNA methylation patterns have been shown to be of biological and clinical importance. Here we report on the integrated analysis of molecular alterations including the methylation status of 27 gene promoters analyzed by highly quantitative pyrosequencing, and the association to gene expression, germline genotype and clinical parameters including survival. Breast cancer specific deregulation of DNA methylation (both hyper- and hypomethylation) was found in twenty genes including ACVR1, OGG1, IL8 and TFF1. The methylation level in the promoter regions was significantly negatively correlated to gene expression for twelve genes (such as MST1R, ST6GAL1 and TFF1) indicating that a gain of aberrant methylation (hypermethylation) inhibits gene expression. Multiple associations between molecular and clinical parameters were identified, and multivariate statistical analysis demonstrated that methylation was more strongly associated to clinical parameters than gene expression for the investigated genes. The methylation level of BCAP31 and OGG1 showed significant association to survival, and these associations were validated in a larger patient cohort (The Cancer Genome Atlas). Our study provides evidence for the promise of DNA methylation alterations for clinical applications.

Corral R, Lewinger JP, Van Den Berg D, et al.
Comprehensive analyses of DNA repair pathways, smoking and bladder cancer risk in Los Angeles and Shanghai.
Int J Cancer. 2014; 135(2):335-47 [PubMed] Article available free on PMC after 15/07/2015 Related Publications
Tobacco smoking is a bladder cancer risk factor and a source of carcinogens that induce DNA damage to urothelial cells. Using data and samples from 988 cases and 1,004 controls enrolled in the Los Angeles County Bladder Cancer Study and the Shanghai Bladder Cancer Study, we investigated associations between bladder cancer risk and 632 tagSNPs that comprehensively capture genetic variation in 28 DNA repair genes from four DNA repair pathways: base excision repair (BER), nucleotide excision repair (NER), non-homologous end-joining (NHEJ) and homologous recombination repair (HHR). Odds ratios (ORs) and 95% confidence intervals (CIs) for each tagSNP were corrected for multiple testing for all SNPs within each gene using pACT and for genes within each pathway and across pathways with Bonferroni. Gene and pathway summary estimates were obtained using ARTP. We observed an association between bladder cancer and POLB rs7832529 (BER) (pACT = 0.003; ppathway = 0.021) among all, and SNPs in XPC (NER) and OGG1 (BER) among Chinese men and women, respectively. The NER pathway showed an overall association with risk among Chinese males (ARTP NER p = 0.034). The XRCC6 SNP rs2284082 (NHEJ), also in LD with SREBF2, showed an interaction with smoking (smoking status interaction pgene = 0.001, ppathway = 0.008, poverall = 0.034). Our findings support a role in bladder carcinogenesis for regions that map close to or within BER (POLB, OGG1) and NER genes (XPC). A SNP that tags both the XRCC6 and SREBF2 genes strongly modifies the association between bladder cancer risk and smoking.

Brunotto M, Zarate AM, Bono A, et al.
Risk genes in head and neck cancer: a systematic review and meta-analysis of last 5 years.
Oral Oncol. 2014; 50(3):178-88 [PubMed] Related Publications
The aim of this work was to identify risk genes related to the development and progression of squamous cell carcinoma head and neck (SCCHN) and do a meta-analysis of available estimates. Eligible gene/polymorphism studies were identified by electronic searches. Individual participant data of 8540 patients with HNC and 9844 controls from 19 genetic studies were analyzed, yielding adjusted (tobacco, gender, age and alcohol) odds ratios (OR) and 95% confidence intervals (CIs) comparing cases with controls. A meta-analysis was done on the studies that applied fixed and random models. People have an increase of polymorphism expression related to inflammation (NFKB1-294-ATTG, TNFα308-A2A2/A2A1, and TNFβ252- B2B2/B2B1) or carcinogenic metabolism (GSTM1 null, and CYP1A1 m1/m1), representative of malignancy development. Furthermore, the increased expression of genes associated with the stabilization and repair of the cellular (OGG1-Asp267Asn, Ser279Gly Ile253Phe, 1578A>T, 1582C>T Ala399Glu (1542C>A) 1582insG 1543_1544delCT), and genes associated with the regulation of proliferation, apoptosis or tumor survival (miRNA499-CT/CC, CRYABC802G-CG/GG) are considered as risk factors. In this scheme, only the polymorphisms of ADH7A92G-GG and DEC1606-T/C genes are protective against malignancy transformation. The TP53, GSTM1 and CYPA1genes have been evaluated in more than one study and analyzed for homogeneity in each genotype. The meta-analysis showed no significant association between different allelic variants of Arg72Pro rs1042522 and SCCHN risk. In a model of tumorigenesis, an increased risk of SCCHN is associated with DNA repair and DNA stabilization genes. In addition, the polymorphisms involved in inflammation and carcinogenic metabolism processes represent an increased risk of SCCHN.

Yan Y, Chen X, Li T, et al.
Association of OGG1 Ser326Cys polymorphism and pancreatic cancer susceptibility: evidence from a meta-analysis.
Tumour Biol. 2014; 35(3):2397-402 [PubMed] Article available free on PMC after 15/07/2015 Related Publications
The 8-oxoguanine DNA glycosylase (OGG1) gene has been considered to be associated with cancer susceptibility. The OGG1 Ser326Cys polymorphism has been reported to be associated with pancreatic cancer (PC), but the published studies have yielded inconsistent results. For better understanding of the effect of OGG1 Ser326Cys polymorphism on PC susceptibility, a meta-analysis was performed. All eligible studies were identified through a search of PubMed, Excerpta Medica Database (Embase), Elsevier Science Direct, and Chinese Biomedical Literature Database before May 2013. The association between the OGG1 Ser326Cys polymorphism and PC risk was conducted by odds ratios (ORs) and 95% confidence intervals (CIs). A total of five case-control studies with 1,690 cases and 3,650 controls were eventually collected. Overall, we found that OGG1 Ser326Cys polymorphism was not associated with PC susceptibility (Cys/Cys vs. Ser/Ser: OR = 0.95, 95% CI = 0.80-1.14; Cys/Cys vs. Ser/Ser + Ser/Cys: OR = 0.95, 95% CI = 0.78-1.14; Cys/Cys + Ser/Cys vs. Ser/Ser (OR = 1.00, 95% CI = 0.89-1.12)). In the subgroup analysis based on ethnicity, source of control, sample size, and genotyping method, no significant association was found in any genetic models. This meta-analysis suggests that the OGG1 Ser326Cys polymorphism may not associated with PC susceptibility. Considering the limited sample size and ethnicity included in the meta-analysis, further larger scaled and well-designed studies are needed to confirm our results.

Li Q, Wang JM, Peng Y, et al.
Association of DNA base-excision repair XRCC1, OGG1 and APE1 gene polymorphisms with nasopharyngeal carcinoma susceptibility in a Chinese population.
Asian Pac J Cancer Prev. 2013; 14(9):5145-51 [PubMed] Related Publications
BACKGROUND: Numerous carcinogens and reactive oxygen species (ROS) may cause DNA damage including oxidative base lesions that lead to risk of nasopharyngeal carcinoma. Genetic susceptibility has been reported to play a key role in the development of this disease. The base excision repair (BER) pathway can effectively remove oxidative lesions, maintaining genomic stability and normal expression, with X-ray repair crosscomplementing1 (XRCC1), 8-oxoguanine glycosylase-1 (OGG1) and apurinic/apyimidinic endonuclease 1 (APE1) playing important roles.
AIMS: To analyze polymorphisms of DNA BER genes (OOG1, XRCC1 and APE1) and explore their associations, and the combined effects of these variants, with risk of nasopharyngeal carcinoma.
MATERIALS AND METHODS: We detected SNPs of XRCC1 (Arg399Gln), OGG1 (Ser326Cys), APE1 (Asp148Glu and -141T/G) using the polymerase chain reaction (PCR) with peripheral blood samples from 231 patients with NPC and 300 healthy people, furtherly analyzing their relations with the risk of NPC in multivariate logistic regression models.
RESULTS: After adjustment for sex and age, individuals with the XRCC1 399Gln/Gln (OR=1.96; 95%CI:1.02- 3.78; p=0.04) and Arg/Gln (OR=1.87; 95%CI:1.29-2.71; p=0.001) genotype variants demonstrated a significantly increased risk of nasopharyngeal carcinoma compared with those having the wild-type Arg/Arg genotype. APE1- 141G/G was associated with a significantly reduced risk of NPC (OR=0.40;95%CI:0.18-0.89) in the smoking group. The OR calculated for the combination of XRCC1 399Gln and APE1 148Gln, two homozygous variants ,was significantly additive for all cases (OR=2.09; 95% CI: 1.27-3.47; p=0.004).
CONCLUSION: This is the first study to focus on the association between DNA base-excision repair genes (XRCC1, OGG1 and APE1) polymorphism and NPC risk. The XRCC1 Arg399Gln variant genotype is associated with an increased risk of NPC. APE1- 141G/G may decrease risk of NPC in current smokers. The combined effects of polymorphisms within BER genes of XRCC1 399Gln and APE1 148Gln may contribute to a high risk of nasopharyngeal carcinoma.

Hosono S, Matsuo K, Ito H, et al.
Polymorphisms in base excision repair genes are associated with endometrial cancer risk among postmenopausal Japanese women.
Int J Gynecol Cancer. 2013; 23(9):1561-8 [PubMed] Related Publications
OBJECTIVES: Polymorphisms in base excision repair (BER) genes are associated with risk for several types of cancers but have not been studied with respect to endometrial cancer among Japanese women. Therefore, we conducted a case-control study to explore the association between polymorphisms in BER genes and the risk for endometrial cancer.
METHODS/MATERIALS: This study included a total of 91 postmenopausal subjects with endometrial cancer and 261 controls without cancer who visited the Aichi Cancer Center between 2001 and 2005. We focused on single nucleotide polymorphisms within coding regions of 5 BER genes (OGG1, MUTYH, XRCC1, APEX1, and PARP1). To assess lifestyle in the etiology of endometrial cancer, we used a self-administered questionnaire. Associations were evaluated using multivariate unconditional logistic regression models. We also assessed whether there were intergenic associations or an interaction with obesity.
RESULTS: We observed a significant association between endometrial cancer risk and XRCC1 rs1799782 (C > T, Arg194Trp) and XRCC1 rs25487 (G > A, Arg399Gln). We uncovered a significant association between obesity (body mass index, ≥ 25) and rs25487. The XRCC1 polymorphisms were in complete linkage disequilibrium, and the XRCC1 haplotype TG associated significantly with endometrial cancer risk. The interaction between the CA haplotype and body mass index was marginally significant, whereas interaction between haplotype in XRCC1 and rs1136410 (PARP1) was not significant.
CONCLUSIONS: We found a significant association between endometrial cancer risk and XRCC1 polymorphisms and haplotype TG in postmenopausal Japanese women.

Yin ZB, Hua RX, Li JH, et al.
Smoking and hOGG1 Ser326Cys polymorphism contribute to lung cancer risk: evidence from a meta-analysis.
Tumour Biol. 2014; 35(2):1609-18 [PubMed] Related Publications
The human 8-oxoguanine DNA glycosylase (hOGG1) gene plays an important role in the repair of oxidatively damaged DNA base lesions and its functional single nucleotide polymorphisms (SNPs) may alter DNA repair capacity and thus contributes to cancer susceptibility. Numerous studies have investigated the association between hOGG1 Ser326Cys polymorphism and lung cancer susceptibility; however, the conclusions are still inconclusive. We searched eligible publications from MEDLINE, EMBASE, and CBM and performed a meta-analysis to assess the associations between hOGG1 Ser326Cys polymorphism and lung cancer risk. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated to estimate risk associations, and false-positive report probability (FPRP) analysis was also carried out to evaluate significant findings. A total of 31 investigations with 10,220 cases and 12,284 controls were identified. When all studies were pooled, a significantly increased overall lung cancer risk was found (Cys/Cys vs. Ser/Ser: OR = 1.24, 95 % CI = 1.05-1.47, P = 0.013; recessive model: OR = 1.22, 95 % CI = 1.05-1.41, P = 0.008, and Cys vs. Ser: OR = 1.11, 95 % CI = 1.02-1.21, P = 0.022), and further stratification analysis showed that the association was stronger in Asians, never smokers, and more-cigarette takers. These results were confirmed by FPRP analysis. Despite some limitations, this meta-analysis provides solid evidence that hOGG1 Ser326Cys polymorphism may contribute to lung cancer risk, particularly for Asian populations, never smokers, and more-cigarette takers. Nevertheless, these findings warrant further validation in single large investigations.

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