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. 2015 Nov 15;8(11):21145–21151.

Genetic association between hOGG1 C8069G polymorphism and colorectal cancer risk

Xiaoge Sun 1,*, Hao Yang 2,*, Yu Lin 1, Jianguo Zhao 1, Yinna Bao 1, Xiulan Liu 1, Zhen Qi 1, Shaojun Wang 1, Congxiu Huang 1, Zhilong Yu 1
PMCID: PMC4723892  PMID: 26885047

Abstract

Background: hOGG1 C8069G polymorphism has been extensively investigated in single studies as well as meta-analyses in terms of the association with colorectal cancer (CRC). But the results remain contradictory. This study was undertaken to comprehensively evaluate the association of the commonly studied hOGG1 C8069G polymorphism and the susceptibility to CRC. Methods: By searching the electronic databases of PubMed, Embase, and Web of science, 16 available publications consisting of 4,866 cases and 7,363 controls were finally included in our meta-analysis. Stratified analyses by ethnicity and source of control were also carried out to further assess the association between hOGG1 C8069G polymorphism and CRC risk. Results: hOGG1 C8069G polymorphism was not observed to have statistical significance with the susceptibility to CRC (ORCC vs. GG = 0.97, 95% CI = 0.91-1.05; P = 0.995; ORCC + CG vs. GG = 0.98, 95% CI = 0.93-1.04; P = 0.993; ORCC vs. CG + GG = 0.96, 95% CI = 0.90-1.02; P = 0.339; ORallele C vs. allele G = 0.98, 95% CI = 0.94-1.02; P = 0.912; ORCG vs. GG = 0.95, 95% CI = 0.88-1.03; P = 0.526). Similarly, no association was found in the subgroup analysis by ethnicity or the source of control. Conclusions: The results of our meta-analysis did not demonstrate any evidence for significant association between hOGG1 C8069G polymorphism and CRC risk. Future large-scale studies are expected to be conducted to further confirm our findings.

Keywords: hOGG1, C8069G, CRC, polymorphism, susceptibility

Introduction

Colorectal cancer (CRC) is one of the most common cancers worldwide, leading to the overwhelming majority of deaths in relation to cancer [1]. Of the complex etiology of CRC, exposure to assaults from common environmental risk factors and various endogenous and exogenous mutagens or carcinogens have been evidenced to be the major contributions for the susceptibility to CRC [2-4]. Among the threatening agents, oxidant is the most common one that could induce genomic instability, and causes damage to DNA and mutations, activation of oncogenes as well as inactivation of tumor suppressor genes, or carcinogenesis [5,6]. So the repair of DNA plays a key role in genome stability that is closely related to cancer risk including the CRC.

DNA 8-hydroxydeoxyguanine caused by oxidative stress is mutagenic or carcinogenic, leading to G: C to T: A transversions. The 8-hydroxydeoxyguanine lesions undergo the base-excision repair, particularly by a critical enzyme the 8-oxoguanine DNA glycosylase that is essential in the repair of 8-oxoguanine and other oxidative DNA damages [7]. hOGG1 gene on chromosome 3p26, plays an important role in DNA repair by various processes [8,9].

Many previous studies have investigated several polymorphisms of hOGG1 gene, such as 2 homozygous mutations at codons 85 and 131, codon 46 Arg/Gln, codon 154 Arg/His, codon 229 Arg/Gln, 7143A/G and 11657A/G [10-14]. However, the most frequently explored polymorphism is hOGG1, which has been extensively investigated in single studies as well as meta-analysis in terms of the association with CRC. But the results of them remain contradictory. Some provided evidence for significant association between hOGG1 polymorphism and CRC risk [15-19], while the others indicated no significance [20-26]. This might be caused by the limited samples in these studies, thus an updated meta-analysis with more study subjects was performed to confirm the association between the hOGG1 polymorphism and CRC risk.

Materials and methods

Literature search strategy

To extract all publications on the association between hOGG1 C8069G polymorphism and CRC risk, we searched the electronic databases of the PubMed, Embase, and Web of Science until February 2014. The terms used in the search were “hOGG1”, or “C8069G”, “polymorphism” or “genetic variation”, and “colorectal cancer”. Additional relevant publications were manually screened in the references of each publication. The eligible studies included in the meta-analysis were limited to English and conducted on human subjects. Moreover, we contacted the authors of the literature when crucial data were not reported in the original papers. If more than one publication were conducted on the same patient populations, only the latest and the largest one was selected.

Inclusion and exclusion criteria

The inclusion criteria used in our meta-analysis were as follows: (1) a case-control design; (2) an investigation of the association between hOGG1 C8069G polymorphism and colorectal cancer risk; (3) adequate data on the numbers of case and control group; (4) clear numbers of the genotypes. The following were the designed exclusion criteria: (1) the studies on the colon or rectal cancer; (2) case-only study; (3) abstracts, editorials, letters, and review articles. In the end, 16 qualified studies were selected in this meta-analysis.

Data extraction

Two authors extracted the data independently. The extracted data from each study included first author, journal, year of publication, study country, source of control, ethnicity, genotyping method, the numbers of total study subjects in cases and controls, information on the distribution of genotypes, and the selection and characteristics of cancer cases and controls. The differences emerging in the search were resolved by discussion until consensus was reached.

Meta-analysis

The odds ratios (ORs) of CRC in relation to hOGG1 C8069G polymorphism were detected for the single studies separately. As for hOGG1 C8069G polymorphism, we evaluated the risk of the following five genetic models: CC vs. GG, CC + GG vs. GG, CC vs. CG + GG, allele C vs. allele G, CG vs. GG, respectively. Apart from the comparisons for total subjects, stratified analyses by ethnicity and the source of control were also performed.

Statistical analysis

The crude odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were calculated for each study. We also estimated the between-study heterogeneity across the eligible comparisons using the X2-based Q test [27] and P < 0.1 was considered significant. The combined values of the included studies were estimated by fixed-effects model [28] or random-effects model [29]. The former was adopted if P > 0.1, or the latter was used. The funnel plots and Egger’s test were used to detect publication bias [30]. Hardy-Weinberg equilibrium (HWE) was tested by the chi-square test. To evaluate the effects of single studies on the overall CRC risk, sensitivity analysis was used by excluding one study each time independently and recalculating the ORs and 95% CIs. All statistical analyses were performed by STATA version 12.0 (Stata Corporation, College Station, TX). All the tests were two-sided and P < 0.1 was considered statistically significant.

Results

Studies characteristics

At the end of our literature search, there were actually 21 selected studies in total. But five studies were excluded because three of them failed to provide enough information about genotype distribution [31-33] and two were reviews [34,35]. Thus this updated meta-analysis was conducted on the basis of 16 case-control eligible studies including 4,866 cases and 7,363 controls. The basic information like first author, year of publication, country, ethnicity, source of control, genotyping methods, numbers of cases and controls, distribution of genotypes and alleles, and HWE were all presented in Table 1. Of the included 16 studies, seven were conducted on Asians [18,21,25,26,36,37] and 9 on Caucasians [15-17,20,22-24,38,39]. For the source of control, ten were population-based [16,17,21,23,39,40] and six were hospital-based [15,18,20,22,24-26,36-38]. All cases were histopathologically confirmed and controls were matched with the cases by age, gender and other variables. The PCR-RFLP was most commonly performed in genotyping among the individual studies.

Table 1.

Main characteristics of all studies included in the meta-analysis

First author Country Ethnicity Control source Genotyping method Case sample size Control sample size HWE
Kim Korea Asian PB PCR-RFLP 125 247 0.320
Hansen Norway Caucasian PB TaqMan 165 396 0.262
Moreno Spain Caucasian HB PCR-RFLP 362 323 0.360
Stern Singapore Asian PB TaqMan 303 1159 0.380
Park Korea Asian PB TaqMan 439 676 0.823
Kasahara Japan Asian PB PCR-RFLP 68 81 0.002
Pardini Czech Caucasian HB PCR-RFLP 532 532 0.437
Curtin USA Caucasian PB TaqMan 1582 1951 0.563
Sliwinski Poland Caucasian HB PCR-RFLP 100 100 0.607
Hansen Denmark Caucasian PB TaqMan 373 776 0.253
Engin Turkey Asian HB PCR-RFLP 110 116 0.203
Obtulowicz Poland Caucasian PB PCR-RFLP 74 97 0.139
Brevik USA Caucasian PB TaqMan 308 362 0.916
Canbay Turkey Asian PB PCR-RFLP 79 247 0.990
Gil Polish Caucasian HB PCR-RFLP 132 100 0.048
Sameer India Asian HB PCR-RFLP 114 200 0.121
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PCR-RFLP: polymerase chain reaction-restriction fragment length polymorphism; PB: population-based; HB: hospital-based; HWE: Hardy-Weinberg equilibrium.

Meta-analysis results

The genotyping data of hOGG1 C8069G polymorphism were obtained from 16 publications. There was no between-study heterogeneity across the eligible comparisons in the meta-analysis, so the fixed-effects model was selected to calculate the pooled ORs. As showed in Table 2, pooling all eligible studies into the meta-analysis, we observed that there was no evidence for significant association between hOGG1 C8069G polymorphism and overall CRC risk (ORCC vs. GG = 0.97, 95% CI = 0.91-1.05; P = 0.995; ORCC + CG vs. GG = 0.98, 95% CI = 0.93-1.04; P = 0.993; ORCC vs. CG + GG = 0.96, 95% CI = 0.90-1.02; P = 0.339; ORallele C vs. allele G = 0.98, 95% CI = 0.94-1.02; P = 0.912; ORCG vs. GG = 0.95, 95% CI = 0.88-1.03; P = 0.526). In addition, neither significant association was observed in the stratified analysis based on ethnicity, nor in the subgroup analysis by source of control (Figure 1).

Table 2.

Meta-analysis results for hOGG1 C8069G polymorphism and CRC risk

CC vs. GG CC + CG vs. GG CC vs. CG + GG Allele C vs. Allele G CG vs. GG
OR (95% CI) Ph OR (95% CI) Ph OR (95% CI) Ph OR (95% CI) Ph OR (95% CI) Ph
Ethnicity
    Asian 0.98 (0.82, 1.16) 0.807 0.98 (0.88, 1.09) 0.723 0.90 (0.77, 1.05) 0.049 0.98 (0.90, 1.07) 0.487 1.02 (0.90, 1.15) 0.999
    Caucasian 0.97 (0.90, 1.05) 0.990 0.98 (0.92, 1.05) 0.997 0.97 (0.90, 1.04) 0.902 0.98 (0.93, 1.03) 0.945 0.91 (0.82, 1.01) 0.159
Control source
    Population 0.97 (0.89, 1.06) 0.873 0.98 (0.92, 1.05) 0.854 0.95 (0.88, 1.02) 0.112 0.98 (0.93, 1.02) 0.577 0.95 (0.87, 1.04) 0.133
    Hospital 0.98 (0.85, 1.12) 1.000 0.98 (0.88, 1.10) 1.000 0.99 (0.88, 1.12) 0.843 0.99 (0.91, 1.07) 0.985 0.95 (0.80, 1.14) 0.998
    Total 0.97 (0.91, 1.05) 0.995 0.98 (0.93, 1.04) 0.993 0.96 (0.90, 1.02) 0.339 0.98 (0.94, 1.02) 0.912 0.95 (0.88, 1.03) 0.526
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Ph: P-value of heterogeneity test. CI, confidence interval; OR, odds ratio.

Figure 1.

Figure 1

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The fixed-effects model.

Heterogeneity and sensitivity analyses

No between-study heterogeneity was observed among overall studies of hOGG1 C8069G polymorphism in all genetic models (P > 0.1). In the sensitivity analyses, we examined the effects of each study on the pooled OR by repeatedly omitting one study at a time and recalculating the ORs, which confirmed the stability of our results. Two of the 16 studies, whose genotype distributions deviated from HWE, did not apparently affect the overall result of the meta-analysis.

Publication bias

Begg’s funnel plot and Egger’s test were carried out to evaluate the publication bias of all included studies. The symmetrical shape of the funnel plot suggested that there was no obvious publication bias (Figure 2). Meanwhile, the Egger’s test further indicated that there existed no significant publication bias in this meta-analysis (the Egger’s test: CC vs. GG: P = 0.284, Begg’s test: P = 0.344).

Figure 2.

Figure 2

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The funnel plot.

Discussion

In this meta-analysis, all available single studies were summarized to examine the combined association of the well-characterized polymorphism of hOGG1 C8069G and overall CRC risk. A large number of studies have been devoted to investigating whether hOGG1 C8069G polymorphism was associated with the susceptibility to CRC. Some authors, such as Curtin et al. suggested that hOGG1 C8069G polymorphism was not significantly associated with CRC susceptibility [20-26,36-39]. In contrast, different findings were reported in several other publications [15-18]. Meanwhile, conflicts were also indicated in four meta-analysis. Three of them held the same view with Curtin et al. [41-43], yet one study supported that the hOGG1 C8069G polymorphism was associated with an increased CRC susceptibility in different genetic models [40]. The inconsistent results may attribute to the various study designs and the relatively smaller sample of each individual studies and meta-analysis.

Compared with the four previous meta-analyses, the current study has two advantages: (1) we included newly published data; (2) the sample size increased by 246 in CRC cases and 388 in control subjects because of the new data. The strengths provided more convincing evidence for the association between hOGG1 C8069G polymorphism and CRC risk. Our meta-analysis indicated that hOGG1 C8069G polymorphism was not a risk factor for the susceptibility to CRC. This is supported by Kim et al. [20-26,36-43], and simultaneously opposed by other studies [15-19]. The carcinogenesis of cancer including CRC is complicated and multifactorial. The possible explanation for the etiology of CRC is continual exposure to risk factors such as polluted environment and chemical carcinogens, which could lead to gene mutation and carcinogenesis. Therefore, the role of hOGG1 C8069G polymorphism in CRC risk is expected to be further examined in future gene-to-environment association studies.

To further confirm our finding, we conducted subgroup analyses by ethnicity and the source of control. In the stratified analysis of ethnicity, no association was observed in both Asians and Caucasians under all genetic models. However, Wei et al. found that the hOGG1 C8069G polymorphism was associated with overall cancer risk in Asians (ORGG vs. CC = 1.21, 95% CI = 1.10-1.33, P heterogeneity = 0.001) [42]. In addition, Guo et al. indicated that significantly increased risks were found among European plus American subjects, who are mostly Caucasian (ORGG vs. CG + CC = 1.444; 95% CI = 1.017-2.05, P = 0.04) [41]. The frequencies of allele G differs substantially in Asians and Caucasians (49.3% vs. 77.8%), indicating that the distribution of the allele was obviously different in the ethnic groups. Such a difference might alter the association of hOGG1 C8069G and the cancer risk, which might provide evidence for the disagreements.

In the subgroup analysis by source of control, neither did we find significant evidence that hOGG1 C8069G polymorphism was correlated with CRC risk in both hospital-based studies and population-based ones. The selection criteria of control subjects are not the same in the single studies included in our meta-analysis, thus masking the potential association. So it is of great importance to select studies with representative control subjects in the genotype association studies.

There were some limitations in our meta-analysis. Firstly, lack of the original data of the included studies limited our further estimation of the potential interactions like gene-environmental interaction that may contribute to cancer risk, which has been identified in several single studies [22,37]. Secondly, we included only published studies in the meta-analysis, thus leading to publication bias, even if it was not indicated in the statistical test. Thirdly, in the subgroup analysis, the relatively small sample possibly underpowered the association between hOGG1 C8069G polymorphism and CRC risk.

In conclusion, our meta-analysis provided no evidence that hOGG1 C8069G polymorphism was significantly associated with the susceptibility to CRC, neither in the stratification analysis by ethnicity and source of control. Our study focused only on the effects of a single gene, so further multi-gene and gene-environment association studies should be carried out to yield a more comprehensive understanding of the association between the hOGG1 C8069G polymorphism and cancer susceptibility.

Disclosure of conflict of interest

None.

References

  • 1.Martinez SR, Young SE, Hoedema RE, Foshag LJ, Bilchik AJ. Colorectal cancer screening and surveillance: current standards and future trends. Ann Surg Oncol. 2006;13:768–775. doi: 10.1245/ASO.2006.03.087. [DOI] [PubMed] [Google Scholar]
  • 2.Levi F, Pasche C, La Vecchia C, Lucchini F, Franceschi S. Food groups and colorectal cancer risk. Br J Cancer. 1999;79:1283–1287. doi: 10.1038/sj.bjc.6690206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Mohrenweiser HW, Jones IM. Variation in DNA repair is a factor in cancer susceptibility: a paradigm for the promises and perils of individual and population risk estimation? Mutat Res. 1998;400:15–24. doi: 10.1016/s0027-5107(98)00059-1. [DOI] [PubMed] [Google Scholar]
  • 4.Labianca R, Beretta G, Gatta G, de Braud F, Wils J. Colon cancer. Crit Rev Oncol Hematol. 2004;51:145–170. doi: 10.1016/j.critrevonc.2004.03.003. [DOI] [PubMed] [Google Scholar]
  • 5.Fearon ER. Human cancer syndromes: clues to the origin and nature of cancer. Science. 1997;278:1043–1050. doi: 10.1126/science.278.5340.1043. [DOI] [PubMed] [Google Scholar]
  • 6.Marnett LJ. Oxyradicals and DNA damage. Carcinogenesis. 2000;21:361–370. doi: 10.1093/carcin/21.3.361. [DOI] [PubMed] [Google Scholar]
  • 7.Janssen K, Schlink K, Gotte W, Hippler B, Kaina B, Oesch F. DNA repair activity of 8-oxoguanine DNA glycosylase 1 (OGG1) in human lymphocytes is not dependent on genetic polymorphism Ser326/Cys326. Mutat Res. 2001;486:207–216. doi: 10.1016/s0921-8777(01)00096-9. [DOI] [PubMed] [Google Scholar]
  • 8.Dianov GL, Souza-Pinto N, Nyaga SG, Thybo T, Stevnsner T, Bohr VA. Base excision repair in nuclear and mitochondrial DNA. Prog Nucleic Acid Res Mol Biol. 2001;68:285–297. doi: 10.1016/s0079-6603(01)68107-8. [DOI] [PubMed] [Google Scholar]
  • 9.Karahalil B, Hogue BA, de Souza-Pinto NC, Bohr VA. Base excision repair capacity in mitochondria and nuclei: tissue-specific variations. FASEB J. 2002;16:1895–1902. doi: 10.1096/fj.02-0463com. [DOI] [PubMed] [Google Scholar]
  • 10.Chevillard S, Radicella JP, Levalois C, Lebeau J, Poupon MF, Oudard S, Dutrillaux B, Boiteux S. Mutations in OGG1, a gene involved in the repair of oxidative DNA damage, are found in human lung and kidney tumours. Oncogene. 1998;16:3083–3086. doi: 10.1038/sj.onc.1202096. [DOI] [PubMed] [Google Scholar]
  • 11.Nohmi T, Kim SR, Yamada M. Modulation of oxidative mutagenesis and carcinogenesis by polymorphic forms of human DNA repair enzymes. Mutat Res. 2005;591:60–73. doi: 10.1016/j.mrfmmm.2005.03.033. [DOI] [PubMed] [Google Scholar]
  • 12.Hill JW, Evans MK. A novel R229Q OGG1 polymorphism results in a thermolabile enzyme that sensitizes KG-1 leukemia cells to DNA damaging agents. Cancer Detect Prev. 2007;31:237–243. doi: 10.1016/j.cdp.2007.05.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Xu J, Zheng SL, Turner A, Isaacs SD, Wiley KE, Hawkins GA, Chang BL, Bleecker ER, Walsh PC, Meyers DA, Isaacs WB. Associations between hOGG1 sequence variants and prostate cancer susceptibility. Cancer Res. 2002;62:2253–2257. [PubMed] [Google Scholar]
  • 14.Rossner P Jr, Terry MB, Gammon MD, Zhang FF, Teitelbaum SL, Eng SM, Sagiv SK, Gaudet MM, Neugut AI, Santella RM. OGG1 polymorphisms and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2006;15:811–815. doi: 10.1158/1055-9965.EPI-05-0659. [DOI] [PubMed] [Google Scholar]
  • 15.Obtulowicz T, Swoboda M, Speina E, Gackowski D, Rozalski R, Siomek A, Janik J, Janowska B, Ciesla JM, Jawien A, Banaszkiewicz Z, Guz J, Dziaman T, Szpila A, Olinski R, Tudek B. Oxidative stress and 8-oxoguanine repair are enhanced in colon adenoma and carcinoma patients. Mutagenesis. 2010;25:463–471. doi: 10.1093/mutage/geq028. [DOI] [PubMed] [Google Scholar]
  • 16.Pardini B, Naccarati A, Novotny J, Smerhovsky Z, Vodickova L, Polakova V, Hanova M, Slyskova J, Tulupova E, Kumar R, Bortlik M, Barale R, Hemminki K, Vodicka P. DNA repair genetic polymorphisms and risk of colorectal cancer in the Czech Republic. Mutat Res. 2008;638:146–153. doi: 10.1016/j.mrfmmm.2007.09.008. [DOI] [PubMed] [Google Scholar]
  • 17.Moreno V, Gemignani F, Landi S, Gioia-Patricola L, Chabrier A, Blanco I, Gonzalez S, Guino E, Capella G, Canzian F. Polymorphisms in genes of nucleotide and base excision repair: risk and prognosis of colorectal cancer. Clin Cancer Res. 2006;12:2101–2108. doi: 10.1158/1078-0432.CCR-05-1363. [DOI] [PubMed] [Google Scholar]
  • 18.Canbay E, Cakmakoglu B, Zeybek U, Sozen S, Cacina C, Gulluoglu M, Balik E, Bulut T, Yamaner S, Bugra D. Association of APE1 and hOGG1 polymorphisms with colorectal cancer risk in a Turkish population. Curr Med Res Opin. 2011;27:1295–1302. doi: 10.1185/03007995.2011.573544. [DOI] [PubMed] [Google Scholar]
  • 19.Wang W, Wang M, Chen Y, Zhang Z, Wang S, Xu M, Wang B, Zhao Q. The hOGG1 Ser326Cys polymorphism contributes to cancer susceptibility: evidence from 83 case-control studies. Mutagenesis. 2012;27:329–336. doi: 10.1093/mutage/ger083. [DOI] [PubMed] [Google Scholar]
  • 20.Brevik A, Joshi AD, Corral R, Onland-Moret NC, Siegmund KD, Le Marchand L, Baron JA, Martinez ME, Haile RW, Ahnen DJ, Sandler RS, Lance P, Stern MC. Polymorphisms in base excision repair genes as colorectal cancer risk factors and modifiers of the effect of diets high in red meat. Cancer Epidemiol Biomarkers Prev. 2010;19:3167–3173. doi: 10.1158/1055-9965.EPI-10-0606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Engin AB, Karahalil B, Engin A, Karakaya AE. Oxidative stress, Helicobacter pylori, and OGG1 Ser326Cys, XPC Lys939Gln, and XPD Lys751Gln polymorphisms in a Turkish population with colorectal carcinoma. Genet Test Mol Biomarkers. 2010;14:559–564. doi: 10.1089/gtmb.2009.0195. [DOI] [PubMed] [Google Scholar]
  • 22.Curtin K, Samowitz WS, Wolff RK, Ulrich CM, Caan BJ, Potter JD, Slattery ML. Assessing tumor mutations to gain insight into base excision repair sequence polymorphisms and smoking in colon cancer. Cancer Epidemiol Biomarkers Prev. 2009;18:3384–3388. doi: 10.1158/1055-9965.EPI-09-0955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Sliwinski T, Krupa R, Wisniewska-Jarosinska M, Pawlowska E, Lech J, Chojnacki J, Blasiak J. Common polymorphisms in the XPD and hOGG1 genes are not associated with the risk of colorectal cancer in a Polish population. Tohoku J Exp Med. 2009;218:185–191. doi: 10.1620/tjem.218.185. [DOI] [PubMed] [Google Scholar]
  • 24.Hansen RD, Krath BN, Frederiksen K, Tjonneland A, Overvad K, Roswall N, Loft S, Dragsted LO, Vogel U, Raaschou-Nielsen O. GPX1 Pro(198)Leu polymorphism, erythrocyte GPX activity, interaction with alcohol consumption and smoking, and risk of colorectal cancer. Mutat Res. 2009;664:13–19. doi: 10.1016/j.mrfmmm.2009.01.009. [DOI] [PubMed] [Google Scholar]
  • 25.Kasahara M, Osawa K, Yoshida K, Miyaishi A, Osawa Y, Inoue N, Tsutou A, Tabuchi Y, Tanaka K, Yamamoto M, Shimada E, Takahashi J. Association of MUTYH Gln324His and APEX1 Asp148Glu with colorectal cancer and smoking in a Japanese population. J Exp Clin Cancer Res. 2008;27:49. doi: 10.1186/1756-9966-27-49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Stern MC, Conti DV, Siegmund KD, Corral R, Yuan JM, Koh WP, Yu MC. DNA repair single-nucleotide polymorphisms in colorectal cancer and their role as modifiers of the effect of cigarette smoking and alcohol in the Singapore Chinese Health Study. Cancer Epidemiol Biomarkers Prev. 2007;16:2363–2372. doi: 10.1158/1055-9965.EPI-07-0268. [DOI] [PubMed] [Google Scholar]
  • 27.Lau J, Ioannidis JP, Schmid CH. Quantitative synthesis in systematic reviews. Ann Intern Med. 1997;127:820–826. doi: 10.7326/0003-4819-127-9-199711010-00008. [DOI] [PubMed] [Google Scholar]
  • 28.Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–748. [PubMed] [Google Scholar]
  • 29.DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–188. doi: 10.1016/0197-2456(86)90046-2. [DOI] [PubMed] [Google Scholar]
  • 30.Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–634. doi: 10.1136/bmj.315.7109.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Halford SE, Rowan AJ, Lipton L, Sieber OM, Pack K, Thomas HJ, Hodgson SV, Bodmer WF, Tomlinson IP. Germline mutations but not somatic changes at the MYH locus contribute to the pathogenesis of unselected colorectal cancers. Am J Pathol. 2003;162:1545–1548. doi: 10.1016/S0002-9440(10)64288-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Liu X, Xiao N, Guo W, Wu Y, Cai Z, He Q, Zhang L, Chen X, Sun C, Wang J, Zhu C, Jin H, Wang Y. The hOGG1 gene 5’-UTR variant c. -53G > C contributes to the risk of gastric cancer but not colorectal cancer in the Chinese population: the functional variation of hOGG1 for gastric cancer risk. J Cancer Res Clin Oncol. 2011;137:1477–1485. doi: 10.1007/s00432-011-1022-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Stern MC, Butler LM, Corral R, Joshi AD, Yuan JM, Koh WP, Yu MC. Polyunsaturated fatty acids, DNA repair single nucleotide polymorphisms and colorectal cancer in the Singapore Chinese Health Study. J Nutrigenet Nutrigenomics. 2009;2:273–279. doi: 10.1159/000308467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Karahalil B, Bohr VA, Wilson DM 3rd. Impact of DNA polymorphisms in key DNA base excision repair proteins on cancer risk. Hum Exp Toxicol. 2012;31:981–1005. doi: 10.1177/0960327112444476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Loft S, Moller P. Oxidative DNA damage and human cancer: need for cohort studies. Antioxid Redox Signal. 2006;8:1021–1031. doi: 10.1089/ars.2006.8.1021. [DOI] [PubMed] [Google Scholar]
  • 36.Park HW, Kim IJ, Kang HC, Jang SG, Ahn SA, Lee JS, Shin HR, Park JG. The hOGG1 Ser326Cys polymorphism is not associated with colorectal cancer risk. J Epidemiol. 2007;17:156–160. doi: 10.2188/jea.17.156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Kim JI, Park YJ, Kim KH, Song BJ, Lee MS, Kim CN, Chang SH. hOGG1 Ser326Cys polymorphism modifies the significance of the environmental risk factor for colon cancer. World J Gastroenterol. 2003;9:956–960. doi: 10.3748/wjg.v9.i5.956. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Hansen R, Saebo M, Skjelbred CF, Nexo BA, Hagen PC, Bock G, Bowitz Lothe IM, Johnson E, Aase S, Hansteen IL, Vogel U, Kure EH. GPX Pro198Leu and OGG1 Ser326Cys polymorphisms and risk of development of colorectal adenomas and colorectal cancer. Cancer Lett. 2005;229:85–91. doi: 10.1016/j.canlet.2005.04.019. [DOI] [PubMed] [Google Scholar]
  • 39.Gil J, Ramsey D, Stembalska A, Karpinski P, Pesz KA, Laczmanska I, Leszczynski P, Grzebieniak Z, Sasiadek MM. The C/A polymorphism in intron 11 of the XPC gene plays a crucial role in the modulation of an individual’s susceptibility to sporadic colorectal cancer. Mol Biol Rep. 2012;39:527–534. doi: 10.1007/s11033-011-0767-5. [DOI] [PubMed] [Google Scholar]
  • 40.Sameer AS, Nissar S, Abdullah S, Chowdri NA, Siddiqi MA. DNA repair gene 8-oxoguanine DNA glycosylase Ser326Cys polymorphism and colorectal cancer risk in a Kashmiri population. DNA Cell Biol. 2012;31:541–546. doi: 10.1089/dna.2011.1349. [DOI] [PubMed] [Google Scholar]
  • 41.Guo CL, Han FF, Wang HY, Wang L. Metaanalysis of the association between hOGG1 Ser326Cys polymorphism and risk of colorectal cancer based on case--control studies. J Cancer Res Clin Oncol. 2012;138:1443–1448. doi: 10.1007/s00432-012-1197-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Wei B, Zhou Y, Xu Z, Xi B, Cheng H, Ruan J, Zhu M, Hu Q, Wang Q, Wang Z, Yan Z, Jin K, Zhou D, Xuan F, Huang X, Shao J, Lu P. The effect of hOGG1 Ser326Cys polymorphism on cancer risk: evidence from a meta-analysis. PLoS One. 2011;6:e27545. doi: 10.1371/journal.pone.0027545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Zhang Y, He BS, Pan YQ, Xu YQ, Wang SK. Association of OGG1 Ser326Cys polymorphism with colorectal cancer risk: a meta-analysis. Int J Colorectal Dis. 2011;26:1525–1530. doi: 10.1007/s00384-011-1258-9. [DOI] [PubMed] [Google Scholar]

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