The hOGG1 Ser326Cys polymorphism and lung cancer risk: a meta-analysis.

The potentially functional polymorphism Ser326Cys in the human 8-oxoguanine DNA glycosylase (hOGG1) gene has been implicated in lung cancer risk, but published studies have mixed findings. To summarize published data, we did a comprehensive meta-analysis. Two investigators extracted data independently from 17 case control studies published in the PubMed using the search phrases "hOGG1/OGG1/OGG and polymorphism/genetic variation and lung cancer." The meta-analysis included 6,375 cancer cases and 6,406 control subjects. The results showed that individuals carrying the hOGG1 Cys/Cys genotype did not have significantly increased risk of lung cancer [odds ratios (OR), 1.15; 95% (confidence interval) CI, 0.94-1.41] compared with those with the Ser/Ser genotype; similarly, no significant association with lung cancer risk was found either in the recessive (OR, 1.09; 95% CI, 0.90-1.32 for Cys/Cys versus Ser/Cys+Ser/Ser) or dominant model of the Ser326 allele (OR, 1.06; 95% CI, 0.93-1.21 for Cys/Cys+Ser/Cys versus Ser/Ser). However, significantly increased risks were found among Asian subjects (OR, 1.18; 95% CI, 1.01-1.38 for Cys/Cys+Ser/Cys versus Ser/Ser) in a dominant model. In stratified analyses by control source, compared with the Ser/Ser genotype, lung cancer risk associated with the hOGG1 Cys/Cys genotype was significantly increased in population-based studies (OR, 1.32; 95% CI, 1.04-1.67) but not in hospital-based studies (OR, 1.18; 95% CI, 0.98-1.42); in stratified analyses by the smoking status, however, the increased risk was observed only among nonsmokers in a dominant model (OR, 1.32; 95% CI, 1.04-1.67). The meta-analysis suggested that a careful matching should be considered in future larger genetic association studies including multiple ethnic groups.     

hOGG1 Ser326Cys polymorphism and breast cancer risk among Asian women

To evaluate the potential association between breast cancer risk and Ser ³²⁶ Cys polymorphism of hOGG1 gene, encoding for an enzyme involved in the base excision repair of 8-hydroxyguanine, hospital based case-control studies were conducted in two Asian populations consisting of 475 breast cancer cases (271 Korean and 204 Japanese) and 500 controls (314 Korean and 186 Japanese). PCR-based methods were employed for the genotyping analyses and the statistical evaluations were performed by unconditional logistic regression model. The frequency of hOGG1 Ser/Ser, Ser/Cys, and Cys/Cys genotypes were 22.5, 48.7, and 28.8% in all cases, and 23.7, 52.1, and 24.1% in the controls. No statistically significant associations between the genotypes and breast cancer risk were observed, neither when the ethnic groups were examined separately nor when the total study population was included. Neither did stratification by menopausal status reveal any association between hOGG1 genotypes and breast cancer. Our novel findings therefore suggest that hOGG1 Ser ³²⁶ Cys polymorphism is unlikely to play a modifying role in individual susceptibility to breast cancer among Asian women.     

Smoking and hOGG1 Ser326Cys polymorphism contribute to lung cancer risk: evidence from a meta-analysis

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.     

Lack of association between the hOGG1 Ser326Cys polymorphism and gastric cancer risk: a meta-analysis

Aim: To clarify any association between the hOGG1 Ser326Cys polymorphism and susceptibility to gastriccancer. Methods: A meta-analysis based on 11 eligible case-control studies involving 5,107 subjects was carriedout to summarize the data on the association between hOGG1 Ser326Cys polymorphism and gastric cancer risk.Results: No association was found between hOGG1 Ser326Cys polymorphism and gastric cancer risk (dominantmodel: OR = 0.95, 95% CI: 0.83-1.09, p = 0.486, ph (p values for heterogeneity) = 0.419; additive model: OR =1.02, 95% CI: 0.81-1.30, p = 0.850, ph = 0.181; recessive model: OR = 1.09, 95% CI: 0.80-1.48, p = 0.586, ph =0.053). Subgroup analysis based on ethnicity (Asian and Caucasian) and smoking status (ever smoker and neversmoker) did did notpresent any significant association. Sensitivity analysis did not perturb the results. Conclusions:This study strongly suggested there might be no association between the hOGG1 Ser326Cys polymorphism andgastric cancer risk. However, larger scale studies are needed for confirmation.     

hOGG1 Ser326Cys polymorphism and lung cancer susceptibility.

The human homologue of the yeast OGG1 gene, hOGG1, has been cloned, and its genetic structure has been determined. Several polymorphisms in the hOGG1 gene were detected in the Japanese populations, and among them, the Ser-Cys polymorphism at codon 326 has been shown to have a functional difference in complementation of mutant Escherichia coli that is defective in the repair of 8-hydroxyguanine. Activity in the repair of 8-hydroxyguanine is greater in hOGG1-Ser326 protein than in hOGG1(326) protein. Because many environmental carcinogens produce 8-hydroxyguanine residue and mismatching to this modified base potentially causes oncogenic mutations, the capacity to repair these lesions can be involved in cancer susceptibility in human beings. We, therefore, examined allele distributions of the Ser326Cys polymorphism in a case-control study of male lung cancer in Okinawa. The analyses based on 241 cases and 197 hospital controls disclosed the following findings. (a) Those with the Cys/Cys genotype were at an increased risk of squamous cell carcinoma and nonadenocarcinoma compared to those with the Ser/Cys and those with the Ser/Ser genotypes combined. The odds ratios adjusted for age and smoking history were 3.01 (95% confidence interval, 1.33-6.83) and 2.18 (95% confidence interval, 1.05-4.54), respectively. (b) The odds ratios for other histological subtypes of lung cancer or those in total were not significant. Those for Cys/Cys or Ser/Cys genotype against Ser/Ser did not reach statistical significance in any cell type. (c) The distributions of this polymorphism varied for different populations (Chinese, Japanese, Micronesians, Melanesians, Hungarians, and Australian Caucasians), with much less prevalence of Cys allele in the latter three populations. Although our sample size was limited, these results indicate that the Ser326Cys variant may be related to squamous cell lung cancer susceptibility. The Cys/Cys genotype appears to be more susceptible to squamous cell carcinoma, although the risk is less than that previously reported to be associated with the CYP1A1 gene. Further studies are needed to assess the importance of the interpopulation variation to cancer susceptibility.     

An association between hOGG1 Ser326Cys polymorphism and the risk of bladder cancer in non-smokers: a meta-analysis

ABSTRACT: BACKGROUND: Bladder cancer results from complex interactions between many genetic and environment factors. The polymorphism Ser326Cys in hOGG1 gene has been reported to be associated with bladder cancer in some studies, though the results remain inconclusive. To explore this relationship of hOGG1 polymorphism and the susceptibility for bladder cancer and the impact of smoking exposures, a cumulative meta-analysis was performed in this study. METHODS: We extracted the data from the Pubmed database up to January 9, 2012 using the search phrases "hOGG1, Ser326Cys polymorphism and bladder cancer". Seven case-control studies were identified, including 2474 patients and 2408 controls. Four of them provided the analysis of smoking effects, with 1372 smokers and 947 non-smokers. The odds ratios (ORs) and associated 95% confidence intervals (CIs) were calculated using fixed- or random- effects models. RESULTS: Regarding the overall association between the hOGG1 326Cys allele and bladder cancer risk, the meta-analysis did not reveal a significant effect in the additive model (OR: 1.06, 95% CI: 0.96-1.26; p=0.49), the recessive genetic model (OR: 1.05, 95% CI: 0.65-1.70; p=0.85) or the dominant genetic model (OR: 1.07, 95% CI: 0.87-1.32; p=0.53). Similarly, no significant relationship was observed in the stratified analysis by ethnicity, study design and Hardy-Weinberg equilibrium (all p>0.05). In the non-smokers, however, hOGG1 326Cys allele significantly increased the risk for bladder cancer and the ORs in the additive model, homozygote contrast and recessive genetic model were 1.59 (p=0.02), 2.53(p=0.003) and 2.41(p=0.0005), respectively. Nevertheless, in the smoker subgroup, similar findings could not be found in all genetic models (all p>0.05). CONCLUSIONS: The association between the hOGG1 326Cys allele and bladder cancer was significant in non-smoker population, while was non-detectable in common or smoker populations. This meta-analysis suggests that the hOGG1 Ser326Cys polymorphism may be a risk factor for bladder cancer without exposure to smoking. Further functional studies are needed to elucidate the gene polymorphism-bladder cancer relationship and gene-environment interactions.     

Association of the hOGG1 Ser326Cys polymorphism with lung cancer risk.

Oxidative stress may be one mechanism by which tobacco smoke causes lung cancer. A common oxidative damage to DNA is the highly mutagenic 7,8-dihydro-8-oxoguanine adduct, which can be repaired by 8-oxoguanine glycosylase I (OGG1). A Ser326Cys substitution polymorphism in the hOGG1 gene has been suggested, based on in vitro data, to reduce the activity of the enzyme. We tested the association of this polymorphism with lung cancer in a population-based, case control study of 298 cases and 405 controls of Caucasian, Japanese, or Native Hawaiian ancestry in Hawaii. Subjects were genotyped with a PCR-RFLP assay, and odds ratios were estimated by logistic regression after adjustment for other observed risk factors, including smoking and vegetable intake. We found marked differences in the frequencies of the hOGG1 Cys variant allele among ethnic groups (45% in Hawaiians, 42% in Japanese, and 22% in Caucasians). The homozygous Cys/Cys genotype was also found to be more common in cases than controls (P = 0.008), with an odds ratio of 2.1 (95% confidence interval: 1.2-3.7) for this genotype compared with the Ser/Ser genotype. Heterozygous individuals were not at increased risk. This association with the Cys/Cys genotype was observed for each sex, ethnic group, and lung cancer cell type. There was also the suggestion that vegetable intake may not be protective against lung cancer among subjects with the Cys/Cys genotype. These data suggest that the presence of two hOGG1 326Cys alleles confers a 2-fold increased risk of lung cancer. Additional studies need to be conducted to confirm this association.     

Ser326Cys polymorphism in hOGG1 gene and risk of esophageal cancer in a Chinese population

Ser326Cys polymorphism in the hOGG1 gene, which is involved in the repair of 8-hydroxyguanine in oxidatively damaged DNA, has been identified and the variant genotype appears to be related to susceptibility to certain cancers. We investigated the association between Ser326Cys polymorphism and squamous-cell carcinoma of the esophagus among a Chinese population. hOGG1 gene polymorphism was detected by PCR-based single-strand conformation polymorphism and DNA sequencing among 201 normal controls and 196 patients with esophageal cancer from Linxian, China, a high-risk area for the disease. The association between this genetic polymorphism and risk of the cancer was examined by a multivariate analysis. We found that the distribution of hOGG1 Ser326Cys genotypes among controls (Ser/Ser, 33.8%; Ser/Cys, 52.8%; and Cys/Cys, 13.4%) was significantly different from that among esophageal cancer cases (39.8%, 38.8% and 21.4%, respectively) (p < 0.05). Homozygosity for the Cys/Cys genotype significantly increased the risk of developing esophageal squamous-cell carcinoma, with the odds ratio (OR) adjusted for age, sex and smoking being 1.9 (95% confidence interval [CI] = 1.3-2.6). Although smoking alone also significantly increased esophageal cancer risk in this case-control study (adjusted OR = 2.6; 95% CI = 1.7-3.9), no significant interaction between smoking and the Cys/Cys genotype was observed in terms of risk. Our results suggest that the hOGG1 326Cys allele might play a role in the carcinogenesis of the esophagus.     

hOGG1 Ser326Cys polymorphism and susceptibility to gallbladder cancer in a Chinese population

The human oxoguanine glycosylase 1(hOGG1) gene encodes a DNA glycosylase that is involved in excision repair of 8-OH-dG (8-hydroxy-2-deoxyguanine) from oxidatively-damaged DNA. To determine whether hOGG1 plays a role in the risk for adenocarcinoma of the gallbladder, we tested the association of this polymorphism with gallbladder cancer in a Chinese population-based, case control study of 204 cases and 209 controls. The subjects were genotyped with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP) assay. The association between the genetic polymorphism of this gene and risk of the cancer was examined by using a multivariate analysis. We found that the distribution of hOGG1 Ser326Cys genotypes among controls (Ser/Ser, 37.3%; Ser/Cys, 53.6% and Cys/Cys, 9.1%) was significantly different from that among gallbladder cancer cases (Ser/Ser, 43.1%; Ser/Cys, 36.3% and Cys/Cys, 20.6%). Significantly increased risk for gallbladder cancer was both the hOGG1 326Ser/Cys (Odds ratio [OR] = 1.9, 95% confidence interval (CI) = 1.0-3.7) and hOGG1 326Cys/Cys genotypes (OR = 4.5, 95% CI = 1.1-22.4). We observed no statistically significant association between hOGG1 genotype and gallbladder cancer association in gallstone absence. In contrast, a near-significant increase in risk for gallbladder cancer was observed for gallstone presence with the hOGG1 326Ser/Cys genotype (OR = 2.2, CI = 1.4-3.5) whereas a significant increase in association for gallbladder cancer was observed for gallstone presence with the 326Cys/Cys genotype (OR = 6.1, CI = 2.1-27.2). These data corresponded with the fact that a significant trend towards increased association for gallbladder cancer was observed with potentially higher-risk hOGG1 genotypes in gallstone presence(p < 0.001, chi(2) trend test)but not in gallstone absence(p = 0.89, chi(2) trend test). A significant increase in risk for gallbladder cancer was observed for larger gallstone (those with stone diameters 2 cm or greater) with the hOGG1 326Ser/Cys(OR = 1.9, 95% CI = 1.1-2.9) and hOGG1 326Cys/Cys genotypes(OR = 5.9, 95% CI = 1.6-18.0). These data are consistent with the observation that a significant trend towards increased risk for gallbladder cancer was observed with potentially higher-risk hOGG1 genotypes in gallbladder cancer patients with larger gallstone (p < 0.001, chi(2) trend test). However, we observed no statistically significant association between hOGG1 genotype and gallbladder cancer risk in gallbladder cancer patients with smaller gallstone (those with stone diameters 2 cm smaller) (hOGG1 326Ser/Cys:OR = 2.2, 95% CI = 0.8-4.0; hOGG1 326Cys/Cys:OR = 2.9, 95% CI = 0.6-29.4; p = 0.06, chi(2) tread test). These results suggest that hOGG1 Ser326Cys polymorphism is associated with gallbladder cancer risk.     

hOGG1 Ser326Cys polymorphism and risk of childhood acute lymphoblastic leukemia in a Chinese population

Oxidative DNA damage caused by reactive oxygen species can produce 8‐oxoguanine (8‐oxoG) in DNA, which is misread and leads to G:C→T:A transversions. This can be carcinogenic. Repair of 8‐oxoG by the base excision repair pathway involves the activity of human 8‐oxoG DNA glycosylase 1 (hOGG1). Accumulating evidence suggests that the hOGG1 Ser326Cys polymorphism affects the activity of hOGG1 and might serve as a genetic marker for susceptibility to several cancers. To determine whether this polymorphism is associated with risk of childhood acute lymphoblastic leukemia (ALL) in Chinese children, we genotyped the hOGG1 Ser326Cys polymorphism (rs1052133) in a case–control study including 415 cases and 511 controls. We found that there was a significant difference in the genotype distributions of the hOGG1 Ser326Cys polymorphism between cases and controls (P = 0.046), and the combined genotypes Ser/Ser and Ser/Cys were associated with a statistically significantly decreased risk of ALL (adjusted odds ratio [OR] = 0.66, 95% confidence interval [CI] = 0.49–0.88, P = 0.005). Furthermore, we found a decreased risk for high risk ALL (adjusted OR = 0.60, 95% CI = 0.40–0.88, P = 0.005), low risk ALL (adjusted OR = 0.68, 95% CI = 0.47–0.99, P = 0.042), and B‐phenotype ALL (adjusted OR = 0.63, 95% CI = 0.46–0.86, P = 0.003) among children with the Ser/Ser and Ser/Cys genotypes. Our results suggest that the hOGG1 Ser326Cys polymorphism is associated with susceptibility to childhood ALL in a Chinese population. (Cancer Sci 2011; 102: 1123–1127)     

hOGG1 Ser326Cys polymorphism, interaction with environmental exposures, and gastric cancer risk in Japanese populations

Oxidative DNA damage caused by reactive oxygen species (ROS) generated by Helicobacter pylori (H. pylori ) infection or smoking may be a cause of gastric cancer development. 8-Hydroxydeoxyguanine (8-OHdG) formation is one of the most common types of oxidative DNA damage, while human oxoguanine glycosylase 1 (hOGG1) is responsible for repairing 8-OHdG lesions. Among several hOGG1 gene polymorphisms, the Ser-->Cys polymorphism at position 326 is related to biological function. To investigate the association between Ser326Cys hOGG1 polymorphism and gastric cancer in relation to the potential risk factors of gastric cancer and antioxidant dietary or nutrient intakes, we conducted a case-control study with 142 histologically-confirmed gastric cancer cases and 271 age, sex-matched healthy controls in Japanese populations. Overall, neither the hOGG1 Ser/Cys nor the Cys/Cys genotype was associated with risk of gastric cancer, compared with the Ser/Ser genotype. A significant interaction was observed between hOGG1 Ser/Cys or Cys/Cys genotype and atrophic gastritis (P for interaction=0.03). No significant interaction was found between hOGG1 genotype and antioxidant dietary or nutrient intakes. The results of the present study suggest that patients with atrophic gastritis in conjunction with the hOGG1 Cys allele might have a higher susceptibility to gastric cancer.     

hOGG1 Ser(326)Cys polymorphism and modification by environmental factors of stomach cancer risk in Chinese

Oxidative stress is involved in many types of DNA damage, e.g., resulting in 8-hydroxyguanine adducts. Since a human counterpart exists for the yeast gene OGG1 (hOGG1) encoding an enzyme that repairs 8-hydroxyguanine, its polymorphism, Ser(326)Cys, might have potential as a genetic marker for cancer susceptibility. To investigate its association with stomach cancer risk and possible interactions with environmental factors, we conducted a case-control study of 101 stomach cancer cases and 198 controls using PCR-single-strand conformation polymorphism and a questionnaire approach. The proportional distribution of the Cys/Cys alleles did not differ between stomach cancer cases and controls, but subgroup analyses revealed that a frequent drinking habit elevated the odds ratio (OR) for stomach cancer in Cys/Cys compared to Ser/Ser and Ser/Cys carriers. The ORs with frequent consumption of pickled vegetables and meat tended to be higher in Cys/Cys than in Ser/Ser and Ser/Cys carriers, these interactions being on the borderline of statistical significance. Our findings suggest that the hOGG1 Ser(326)Cys polymorphism may alter the impact of some environmental factors on stomach cancer development. For confirmation, an additional study with a larger number of subjects is now required.     

HOGG1 Ser326Cys polymorphism and susceptibility to head and neck cancer: a meta-analysis

Purpose: Several research groups have investigated the influence of the human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys polymorphism on head and neck cancer (HNC) susceptibility. However, the results remain inconclusive and controversial. We therefore conducted the present meta-analysis. Methods: Relevant studies were identified through a search of PubMed databases until July 2011 and selected on the basis of established inclusion criteria for publications. Results: A total of 8 case-control studies on the association of hOGG1 Ser326Cys polymorphism with HNC risk were included in the present meta-analysis. Overall significant associations were observed (G allele vs. C allele: OR=1.49, 95%CI=1.08-2.05, P<0.01 for heterogeneity; GG vs.CC: OR=2.30, 95%CI=1.05-5.05, P<0.01 for heterogeneity; CG vs. CC: OR=1.40, 95%CI=1.03-1.90, P<0.01 for heterogeneity; dominant model (GG+CG vs. CC): OR=1.52, 95%CI=1.06-2.16, P<0.01 for heterogeneity; recessive model (GG vs. CG+CC): OR=2.04, 95%CI=1.05-3.96, P=0.01 for heterogeneity) after excluding the studies that were not in agreement with HWE. On performance of a subgroup meta-analysis by ethnicity, significant associations were found (G allele vs. C allele: OR=1.40, 95%CI=1.001-1.95, P<0.01 for heterogeneity; GG vs.CC: OR=2.30, 95%CI=1.05-5.05, P<0.01 for heterogeneity; recessive model (GG vs. CG+CC): OR=2.04, 95%CI=1.05-3.96, P=0.01 for heterogeneity) in Caucasian populations after excluding one study not in agreement with HWE. Conclusions: Our results suggested that the G allele might be associated with an increased risk of HNC in Caucasian populations.     

Association of OGG1 Ser326Cys polymorphism and pancreatic cancer susceptibility: evidence from a meta-analysis

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.     

hOGG1 Ser326Cys polymorphism is associated with risk of bladder cancer in a Chinese population: A case‐control study

Human oxoguanine glycosylase 1 (hOGG1) is a DNA repair enzyme, which plays important roles in the base excision repair (BER) pathway. Several studies reported a common polymorphism Ser326Cys (rs1052133) in hOGG1, which conferred the susceptibility of bladder cancer. We hypothesized that the polymorphism is associated with risk of bladder cancer in a Chinese population. In a case‐control study of 1050 histologically confirmed bladder cancer patients and 1404 age and sex matched healthy controls, we genotyped the hOGG1 Ser326Cys polymorphism using TaqMan technology and assessed its association with bladder cancer risk. We found that the hOGG1 Ser/Cys + Ser/Ser genotypes were associated with a significantly increased risk of bladder cancer (adjusted odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.01–1.41), compared with the Cys/Cys genotype. Furthermore, the increased risk was more pronounced among subjects over age 65 years (OR = 1.31, 95% CI = 1.04–1.66), male subjects (OR = 1.21, 95% CI = 1.00–1.47), ever smokers (OR = 1.29, 95% CI = 1.00–1.68) and heavy smokers (>20 pack‐years) (OR = 1.45, 95% CI = 1.03–2.04). No significant association was observed in the stratification of tumor grade and tumor stage for bladder cancer. In conclusion, our results suggest that hOGG1 Ser326Cys polymorphism may contribute to the susceptibility to bladder cancer in a Chinese population. (Cancer Sci 2012; 103: 1215–1220)     

The hOGG1 Ser326Cys Gene Polymorphism and Breast Cancer Risk in Saudi Population

The purpose of this study was to test the association between human 8-oxoguanine glycosylase 1 (hOGG1) gene polymorphisms and susceptibility to breast cancer in Saudi population. We have also aimed to screen the hOGG1 Ser326Cys polymorphism effect on structural and functional properties of the hOGG1 protein using in silico tools. We have analyzed four SNPs of hOGG1 gene among Saudi breast cancer patients along with healthy controls. Genotypes were screened using TaqMan SNP genotype analysis method. Experimental data was analyzed using Chi-square, t test and logistic regression analysis using SPSS software (v.16). In silco analysis was conducted using discovery studio and HOPE program. Genotypic analysis showed that hOGG1 rs1052133 (Ser326Cys) is significantly associated with breast cancer samples in Saudi population, however rs293795 (T >C), rs2072668 (C>G) and rs2075747 (G >A) did not show any association with breast cancer. The hOGG1 SNP rs1052133 (Ser326Cys) minor allele T showed a significant association with breast cancer samples (OR?=?1.78, χ2?=?7.86, p?=?0.02024). In silico structural analysis was carried out to compare the wild type (Ser326) and mutant (Cys326) protein structures. The structural prediction studies revealed that Ser326Cys variant may destabilize the protein structure and it may disturb the hOGG1 function. Taken together this is the first In silico study report to confirm Ser326Cys variant effect on structural and functional properties of hOGG1 gene and Ser326Cys role in breast cancer susceptibility in Saudi population.