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. 2016 Feb 28;42(4):356–358. doi: 10.12865/CHSJ.42.04.04

Assessment of Oxidative Stress Genes SOD2 and SOD3 Polymorphisms Role in Human Colorectal Cancer

C MARGINEAN 1, I STREATA 1, M IOANA 1, OM MARGINEAN 1, V PADUREANU 1, A SAFTOIU 1, I PETRESCU 1, S TUDORACHE 1, OS TICA 1, F PETRESCU 1
PMCID: PMC6269622  PMID: 30581589

Abstract

Purpose: The aim of this study was to ascertain the oxidative stress genes SOD2 and SOD3 polymorphisms in patients with colorectal cancer and to assess the possible involvement of these polymorphisms that might increase the risk for patients to develop malignant intestinal tumors. Material and methods: A total number of 306 subjects were divided into two groups (109 colorectal cancer patients as the study group and 197 normal healthy individuals as the control group).We genotyped two polymorphisms, SOD2 – 201A>G (rs4880) and SOD3 – 896C>G (rs1799895), by allelic discrimination, with TaqMan RT-PCR specific probes. Results: No significant differences were found with either of the polymorphisms when comparing the association between them and an increased risk of developing colorectal tumors. Conclusion: In Romanian population, the risk of developing colorectal cancer is not increased by SOD2 and SOD3 polymorphisms.

Keywords: colorectal cancer, polymorphism, genotype, SOD2, SOD3

Introduction

Colorectal carcinogenesis induction is a multi-stage process based on several molecular and cellular events that transform a normal cell phenotype into a malignant one [1]. It was revealed that chemicals play an important role in initiation, promotion and progression of carcinogenesis process [2, 3]. One of the mechanisms they use to participate in this multi-step process is oxidative stress induction through occurrence of an imbalance between reactive oxidative species (ROS) production and cellular antioxidant defense systems [4, 5].Oxidative stress role in carcinogenesis is based on generation of DNA damages with mutagenic effects and modulation of cells redox potential that can modify gene expression pattern [1, 6, 7].

Chronic gastrointestinal disorders generates an excess of ROS shown by several studies attempted to find out how oxidative stress modulates molecular mechanisms involved in colorectal cancer [8, 9, 10].

It was demonstrated that an important role in the development of malignant colorectal tumors is played by the dysfunction of the enzymatic and non-enzymatic antioxidant defense systems [11, 12, 13].The enzymatic antioxidant defense system includes enzymes like SOD, CAT, GSH-Px, and GSH involved in maintenance of a normal metabolism and healthy state of the human body [14, 15, 16]. Furthermore, it was revealed that the activity of these enzymes is altered in cancer subjects [17, 18].

Superoxide dismutases (SODs) family is involved in detoxification of superoxide free radicals through conversion of oxidative phosphorylation products (superoxides) to hydrogen peroxide and diatomic oxygen [19, 20].SODs are expressed in many tissues and organs. In humans were identified three forms of superoxide dismutases: one located in cells cytoplasm – SOD1, another isoform in the mitochondria – SOD2 and an extracellular form – SOD3 [21, 22].

Single-nucleotide polymorphisms (SNPs) of the gene that encodes for SOD2 were identified to be related with an increased risk to develop colorectal malignant tumors [23]. It is the case of SOD2- 201 A>G polymorphism that causes an amino-acid substitution (Ala16Val). Thus, revealing that the A allele is linked with a high risk of colorectal cancer development [17, 24].

SOD3 polymorphisms were associated with an increased level of the enzyme in the serum but the studies conducted so far did not find any association with colorectal cancer risk [25, 26].

Material and methods

Patients and samples

A total number of 109 patients diagnosed with sporadic CRC and 197 healthy controls were included in this study, following a standard diagnostic procedure at the Emergency County Hospital of Craiova, Romania. Matched controls patients were recruited based on a negative history of tumor or chronic inflammatory diseases. Demographic data, age, gender, clinical information (family history of CRC and personal history of chronic disorders) were also collected for each patient. Biological samples (peripheral whole blood) were obtained from both groups after they signed a written informed consent. The Ethics Committee of University of Medicine and Pharmacy of Craiova, Romania approved this study.

DNA extraction and genotyping

Peripheral blood leukocytes were used to isolate and purify DNA with the Wizard® Genomic DNA Purification Kit (Promega, Madison, WI, USA), following the manufacturer’s protocol. Samples genotyping was performed using predesigned TaqMan assays from Applied Biosystems (Foster City, CA, USA): C_8709053_10 (SOD2, -201A>G, rs4880) and C_2307506_10 (SOD3, - 896C>G, rs1799895).

Genotyping was carried out in a 5-μL reaction volume using TaqMan probes fluorescently labeled with FAM or VIC and following the protocol recommended by the supplier (Applied Biosystems, Foster City, CA, USA).

Real Time PCR cycling conditions (Real Time ViiA7 - Applied Biosystem) for the denatured reactions were 950C for 10 minutes, followed by 45 cycles of 920C for 15 seconds and 600C for 90 seconds annealing temperature.

Interpretation of samples was done using ViiA™ 7 Software v1.0 with the Allelic Discrimination option.

Statistical analysis

The Hardy-Weinberg equilibrium was tested using Pearson's chi-squared test (χ2). Associations between genotypes and CRC were calculated as odds ratio (OR) with a 95% confidence interval (95%CI). In addition to the overall association analysis, the analysis was performed stratified by tumors histological grade (G1 – well-differentiated, G2 – moderate differentiated, G3 – poorly differentiated) to further assess the association between oxidative stress genotypes and CRC risk in each stratum. In all cases, the most common allele in Caucasian was used as reference. A value higher or equal to 0.05 was considered statistical insignificant.

Results

All 306 samples harvested from colorectal cancer patients during surgery and healthy controls were genotyped. Genotyping was performed in 109 CRC patients and 197 controls.

The average age of our subjects with colorectal cancer was 66 (± 11), while for the control group it was 60.3 (± 11.87). Out of the total 109 cases of colorectal cancer28% (30 cases) had well differentiated tumors, 54% (60 cases) had moderate differentiated tumors, while the other 18% (19 cases) had poorly differentiated tumors.

Both polymorphisms we studied were in Hardy-Weinberg equilibrium for both colorectal cancer and healthy control groups.

Genotype frequency for SOD2 – 201A>G polymorphism is shown in Table 1. Results reveal a p value of 0.397 with an OR value of 0.866 (95%CI: 0.622 – 1.207) that demonstrates no significant differences in the association between the presence of this polymorphism and increased risk for patients to develop colorectal cancer. Furthermore, on a stratified analyze by histological grade we have obtained no significant association for colorectal cancer (Table 1, 2, 3 and 4).SOD3 – 896 C>G polymorphism frequency is shown in Table 5. We did not find any statistical significant difference of this polymorphism and susceptibility to develop colorectal cancer.

Table 1.

Colorectal cancer risk associated with SOD2 – 201A>G genotype

SOD2 – 201A>G Colorectal Cancer Control OR(95%CI) p
GG 37(33.94%) 52 (26.40%) Reference  
AG 45 (41.28%) 97 (49.24%) 0.652 (0.376 – 1.130) 0.128
AA 27 (24.77%) 48 (24.37%) 0.791 (0.420 – 1.488) 0.466
A allele Carriers  99 (45.41%) 193 (48.98%) 0.866 (0.622 – 1.207) 0.397
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Table 2.

Colorectal cancer risk associated with SOD2, G1 tumor grade

SOD2 – 201A>G Well-differentiated tumors (G1) Control OR(95%CI) p
GG 9(30%) 52 (26.40%) Reference  
AG 13 (43.33%) 97 (49.24%) 0.774 (0.310 – 1.932) 0.586
AA 8 (26.67%) 48 (24.37%) 0.963 (0.344 – 2.697) 0.943
A allele Carriers  29 (48.33%) 193 (48.98%) 0.974(0.566 – 1.678) 0.925
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Table 3.

Colorectal cancer risk associated with SOD2, G2 tumor grade

SOD2 – 201A>G Moderate-differentiated tumors (G2) Control OR(95%CI) p
GG 20 (33.33%) 52 (26.40%) Reference  
AG 24 (40%) 97 (49.24%) 0.644(0.325– 1.273) 0.207
AA 16 (26.67%) 48 (24.37%) 0.867 (0.403 – 1.864) 0.714
A allele Carriers  56 (48.33%) 193 (48.98%) 0.911 (0.605 – 1.372) 0.656
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Table 4.

Colorectal cancer risk associated with SOD2, G3 tumor grade

SOD2 – 201A>G Poorly-differentiated tumors (G3) Control OR(95%CI) p
GG 8(42.11%) 52 (26.40%) Reference  
AG 8(42.11%) 97 (49.24%) 0.536 (0.190– 1.511) 0.241
AA 3 (15.79%) 48 (24.37%) 0.406 (0.102 – 1.621) 0.181
A allele Carriers  14 (36.84%) 193 (48.98%) 0.608 (0.305 – 1.209) 0.150
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Table 5.

Colorectal cancer risk associated with SOD3 – 896C>G genotype

SOD3-896C>G Ccolorectal Cancer Control OR(95%CI) p
CC 109(100%) 196 (99.49%) Reference  
CG 0 (0%) 1 (0.51%) 0 0
GG 0 (0%) 0 (0%) 0 0
G allele Carriers  0 (0%) 1 (0.25%) 0 0
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Discussion

SOD2 is a member of superoxide dismutase (SOD) family involved in converting oxidative phosphorylation products (superoxides) to hydrogen peroxide and diatomic oxygen [27]. SOD2 gene is found on chromosome 6q25.3 [28]. SOD2 – 201A>G polymorphism is located in exon-2 of SOD2, with an amino-acid substitution (Ala16Val) that was associated with several pathologies like Parkinson’s disease, Alzheimer’s disease, breast cancer, colorectal cancer, or dilated cardiomyopathy [24, 29, 30, 31, 32, 33].

Several studies carried out between 2001 – 2014 tried to identify an association of SOD2 gene polymorphisms with malignant tumors [34, 35, 36, 37, 38]. The published results were inconsistent and contradictory. Thus, a study conducted by Funke et al it showed that there is no association between SOD2 – 201A>G polymorphism and susceptibility to colorectal cancer [37]. Another study conducted in the Czech Republic by Meplan et al on colorectal cancer revealed an association between SOD2 polymorphism - 201A> G and sporadic colorectal cancer incidence. Their results suggested that this polymorphism may represent a potential biomarker for assessing susceptibility to colorectal cancer [39].

In our study, we found no statistical association between SOD2 polymorphism -201A> G presence or absence and risk in developing colorectal cancer. Furthermore we did a stratified analysis based on tumors histological grade (G1 – well-differentiated, G2 – moderate differentiated, G3 – poorly differentiated). Also the stratified analysis that we performed showed no statistically significant results that could be associated with the risk of developing colorectal cancer.

SOD3 is another member of the SOD family the main defense mechanism against reactive oxygen species (ROS) [40]. It acts by eliminating the strong superoxide radical and producing H2O2 that can then be degraded by enzymes like CAT or GPXs [41]. It is localized exclusively in extracellular spaces and has a tetrameric structure [42]. SOD3 gene is found on chromosome 4p15.2 [28]. Increased expression of SOD3 protein in the white and brown adipose tissue and in the plasma of obese mice was associated in a recent study with gene polymorphisms presence [42]. There are no recent studies conducted on identification of association between this polymorphism and a high susceptibility to cancer.

In our study, the results did not show a statistical association between SOD3 – 896C>G polymorphism and susceptibility to colorectal cancer. Moreover, even the stratified analysis based on tumor grade revealed no statistically relevant data.

Conclusions

In conclusion, our study shows that the genotype frequency for SOD2 – 201A>G and SOD3 – 896C>G were not associated with an increased risk for colorectal cancer. Further extensive studies are needed on different ethnic groups in order to clarify the role of oxidative stress enzymes polymorphisms in colorectal carcinogenesis.

Acknowledgments

All authors had equal contribution.

Conflict of interests

The authors declare that they have no conflict of interests.

References

  • 1.Kawanishi S, Hiraku Y. Oxidative and nitrative DNA damage as biomarker for carcinogenesis with special reference to inflammation. Antioxidants & redox signaling. 2006;8(5-6):1047–1058. doi: 10.1089/ars.2006.8.1047. [DOI] [PubMed] [Google Scholar]
  • 2.Klaunig JE, Kamendulis LM. The role of oxidative stress in carcinogenesis. Annual review of pharmacology and toxicology. 2004;44:239–267. doi: 10.1146/annurev.pharmtox.44.101802.121851. [DOI] [PubMed] [Google Scholar]
  • 3.Klaunig JE, Kamendulis LM, Hocevar BA. Oxidative stress and oxidative damage in carcinogenesis. Toxicologic pathology. 2010;38(1):96–109. doi: 10.1177/0192623309356453. [DOI] [PubMed] [Google Scholar]
  • 4.Kamendulis LM, Jiang J, Xu Y, Klaunig JE. Induction of oxidative stress and oxidative damage in rat glial cells by acrylonitrile. Carcinogenesis. 1999;20(8):1555–1560. doi: 10.1093/carcin/20.8.1555. [DOI] [PubMed] [Google Scholar]
  • 5.Klaunig JE, Xu Y, Isenberg JS, Bachowski S, Kolaja KL, Jiang J, et al. The role of oxidative stress in chemical carcinogenesis. Environmental health perspectives. 1998;106(Suppl 1):289–295. doi: 10.1289/ehp.98106s1289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Kasprzak KS. Oxidative DNA and protein damage in metal-induced toxicity and carcinogenesis. Free radical biology & medicine. 2002;32(10):958–967. doi: 10.1016/s0891-5849(02)00809-2. [DOI] [PubMed] [Google Scholar]
  • 7.Rajaraman P, Hutchinson A, Rothman N, Black PM, Fine HA, Loeffler JS, et al. Oxidative response gene polymorphisms and risk of adult brain tumors. Neuro-oncology. 2008;10(5):709–715. doi: 10.1215/15228517-2008-037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Keshavarzian A, Zapeda D, List T, Mobarhan S. High levels of reactive oxygen metabolites in colon cancer tissue: analysis by chemiluminescence probe. Nutrition and cancer. 1992;17(3):243–249. doi: 10.1080/01635589209514193. [DOI] [PubMed] [Google Scholar]
  • 9.Otamiri T, Sjodahl R. Increased lipid peroxidation in malignant tissues of patients with colorectal cancer. Cancer. 1989;64(2):422–425. doi: 10.1002/1097-0142(19890715)64:2<422::aid-cncr2820640214>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  • 10.Bartsch H, Nair J, Owen RW. Exocyclic DNA adducts as oxidative stress markers in colon carcinogenesis: potential role of lipid peroxidation, dietary fat and antioxidants. Biological chemistry. 2002;383(6):915–921. doi: 10.1515/BC.2002.098. [DOI] [PubMed] [Google Scholar]
  • 11.Ozdemirler Erata G, Kanbagli O, Durlanik O, Bulut T, Toker G, Uysal M. Induced oxidative stress and decreased expression of inducible heat shock protein 70 (ihsp 70) in patients with colorectal adenocarcinomas. Japanese journal of clinical oncology. 2005;35(2):74–78. doi: 10.1093/jjco/hyi022. [DOI] [PubMed] [Google Scholar]
  • 12.Skrzydlewska E, Sulkowski S, Koda M, Zalewski B, Kanczuga-Koda L, Sulkowska M. Lipid peroxidation and antioxidant status in colorectal cancer. World journal of gastroenterology: WJG. 2005;11(3):403–406. doi: 10.3748/wjg.v11.i3.403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Rainis T, Maor I, Lanir A, Shnizer S, Lavy A. Enhanced oxidative stress and leucocyte activation in neoplastic tissues of the colon. Digestive diseases and sciences. 2007;52(2):526–530. doi: 10.1007/s10620-006-9177-2. [DOI] [PubMed] [Google Scholar]
  • 14.Zhou JF, Xu GB, Fang WJ. Relationship between acute organophosphorus pesticide poisoning and damages induced by free radicals. Biomedical and environmental sciences: BES. 2002;15(2):177–186. [PubMed] [Google Scholar]
  • 15.Devasena T, Venugopal Menon P. Fenugreek seeds modulate 1. 2-dimethylhydrazine-induced hepatic oxidative stress during colon carcinogenesis. The Italian journal of biochemistry. 2007;56(1):28–34. [PubMed] [Google Scholar]
  • 16.Muse KE, Oberley TD, Sempf JM, Oberley LW. Immunolocalization of antioxidant enzymes in adult hamster kidney. The Histochemical journal. 1994;26(9):734–753. doi: 10.1007/BF00158205. [DOI] [PubMed] [Google Scholar]
  • 17.Kang D, Lee KM, Park SK, Berndt SI, Peters U, Reding D, et al. Functional variant of manganese superoxide dismutase (SOD2 V16A) polymorphism is associated with prostate cancer risk in the prostate, lung, colorectal, and ovarian cancer study. Cancer epidemiology biomarkers & prevention: a publication of the American Association for Cancer Research cosponsored by the American Society of Preventive Oncology. 2007;16(8):1581–1586. doi: 10.1158/1055-9965.EPI-07-0160. [DOI] [PubMed] [Google Scholar]
  • 18.Forsberg L, de Faire U, Morgenstern R. Oxidative stress, human genetic variation, and disease. Archives of biochemistry and biophysics. 2001;389(1):84–93. doi: 10.1006/abbi.2001.2295. [DOI] [PubMed] [Google Scholar]
  • 19.Li N, Oberley TD, Oberley LW, Zhong W. Overexpression of manganese superoxide dismutase in DU145 human prostate carcinoma cells has multiple effects on cell phenotype. The Prostate. 1998;35(3):221–233. doi: 10.1002/(sici)1097-0045(19980515)35:3<221::aid-pros8>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
  • 20.Bostwick DG, Alexander EE, Singh R, Shan A, Qian J, Santella RM, et al. Antioxidant enzyme expression and reactive oxygen species damage in prostatic intraepithelial neoplasia and cancer. Cancer. 2000;89(1):123–134. [PubMed] [Google Scholar]
  • 21.Huseynova IM, Aliyeva DR, Aliyev JA. Subcellular localization and responses of superoxide dismutase isoforms in local wheat varieties subjected to continuous soil drought. Plant physiology and biochemistry: PPB / Societe francaise de physiologie vegetale. 2014;81:54–60. doi: 10.1016/j.plaphy.2014.01.018. [DOI] [PubMed] [Google Scholar]
  • 22.Niyomploy P, Srisomsap C, Chokchaichamnankit D, Vinayavekhin N, Karnchanatat A, Sangvanich P. Superoxide dismutase isozyme detection using two-dimensional gel electrophoresis zymograms. Journal of pharmaceutical and biomedical analysis. 2014;90:72–77. doi: 10.1016/j.jpba.2013.10.035. [DOI] [PubMed] [Google Scholar]
  • 23.Gohagan JK, Prorok PC, Hayes RB, Kramer BS. The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial of the National Cancer Institute: history, organization, and status. Controlled clinical trials. 2000;21(6 Suppl):251s–272s. doi: 10.1016/s0197-2456(00)00097-0. [DOI] [PubMed] [Google Scholar]
  • 24.Stoehlmacher J, Ingles SA, Park DJ, Zhang W, Lenz HJ. The -9Ala/-9Val polymorphism in the mitochondrial targeting sequence of the manganese superoxide dismutase gene (MnSOD) is associated with age among Hispanics with colorectal carcinoma. Oncology reports. 2002;9(2):235–238. [PubMed] [Google Scholar]
  • 25.Folz RJ, Peno-Green L, Crapo JD. Identification of a homozygous missense mutation (Arg to Gly) in the critical binding region of the human EC-SOD gene (SOD3) and its association with dramatically increased serum enzyme levels. Human molecular genetics. 1994;3(12):2251–2254. doi: 10.1093/hmg/3.12.2251. [DOI] [PubMed] [Google Scholar]
  • 26.Sandstrom J, Nilsson P, Karlsson K, Marklund SL. 10-fold increase in human plasma extracellular superoxide dismutase content caused by a mutation in heparin-binding domain. The Journal of biological chemistry. 1994;269(29):19163–19166. [PubMed] [Google Scholar]
  • 27.Mates JM, Segura JA, Alonso FJ, Marquez J. Oxidative stress in apoptosis and cancer: an update. Archives of toxicology. 2012;86(11):1649–1665. doi: 10.1007/s00204-012-0906-3. [DOI] [PubMed] [Google Scholar]
  • 28.Miao L, St Clair DK. Regulation of superoxide dismutase genes: implications in disease. Free radical biology & medicine. 2009;47(4):344–356. doi: 10.1016/j.freeradbiomed.2009.05.018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Shimoda-Matsubayashi S, Matsumine H, Kobayashi T, Nakagawa-Hattori Y, Shimizu Y, Mizuno Y. Structural dimorphism in the mitochondrial targeting sequence in the human manganese superoxide dismutase gene. A predictive evidence for conformational change to influence mitochondrial transport and a study of allelic association in Parkinson's disease. Biochemical and biophysical research communications. 1996;226(2):561–565. doi: 10.1006/bbrc.1996.1394. [DOI] [PubMed] [Google Scholar]
  • 30.Wiener HW, Perry RT, Chen Z, Harrell LE, Go RC. A polymorphism in SOD2 is associated with development of Alzheimer's disease. Genes, brain and behavior. 2007;6(8):770–775. doi: 10.1111/j.1601-183X.2007.00308.x. [DOI] [PubMed] [Google Scholar]
  • 31.Ambrosone CB, Freudenheim JL, Thompson PA, Bowman E, Vena JE, Marshall JR, et al. Manganese superoxide dismutase (MnSOD) genetic polymorphisms, dietary antioxidants, and risk of breast cancer. Cancer research. 1999;59(3):602–606. [PubMed] [Google Scholar]
  • 32.Mitrunen K, Sillanpaa P, Kataja V, Eskelinen M, Kosma VM, Benhamou S, et al. Association between manganese superoxide dismutase (MnSOD) gene polymorphism and breast cancer risk. Carcinogenesis. 2001;22(5):827–829. doi: 10.1093/carcin/22.5.827. [DOI] [PubMed] [Google Scholar]
  • 33.Hiroi S, Harada H, Nishi H, Satoh M, Nagai R, Kimura A. Polymorphisms in the SOD2 and HLA-DRB1 genes are associated with nonfamilial idiopathic dilated cardiomyopathy in Japanese. Biochemical and biophysical research communications. 1999;261(2):332–339. doi: 10.1006/bbrc.1999.1036. [DOI] [PubMed] [Google Scholar]
  • 34.Zienolddiny S, Campa D, Lind H, Ryberg D, Skaug V, Stangeland LB, et al. A comprehensive analysis of phase I and phase II metabolism gene polymorphisms and risk of non-small cell lung cancer in smokers. Carcinogenesis. 2008;29(6):1164–1169. doi: 10.1093/carcin/bgn020. [DOI] [PubMed] [Google Scholar]
  • 35.Antunes F, Cadenas E. Cellular titration of apoptosis with steady state concentrations of H(2)O(2): submicromolar levels of H(2)O(2) induce apoptosis through Fenton chemistry independent of the cellular thiol state. Free radical biology & medicine. 2001;30(9):1008–1018. doi: 10.1016/s0891-5849(01)00493-2. [DOI] [PubMed] [Google Scholar]
  • 36.Blein S, Berndt S, Joshi AD, Campa D, Ziegler RG, Riboli E, et al. Factors associated with oxidative stress and cancer risk in the Breast and Prostate Cancer Cohort Consortium. Free radical research. 2014;48(3):380–386. doi: 10.3109/10715762.2013.875168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Funke S, Hoffmeister M, Brenner H, Chang-Claude J. Effect modification by smoking on the association between genetic polymorphisms in oxidative stress genes and colorectal cancer risk. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research. cosponsored by the American Society of Preventive Oncology. 2009;18(8):2336–2338. doi: 10.1158/1055-9965.EPI-09-0507. [DOI] [PubMed] [Google Scholar]
  • 38.Bag A, Bag N. Target sequence polymorphism of human manganese superoxide dismutase gene and its association with cancer risk: a review. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2008;17(12):3298–3305. doi: 10.1158/1055-9965.EPI-08-0235. [DOI] [PubMed] [Google Scholar]
  • 39.Meplan C, Hesketh J. The influence of selenium and selenoprotein gene variants on colorectal cancer risk. Mutagenesis. 2012;27(2):177–186. doi: 10.1093/mutage/ger058. [DOI] [PubMed] [Google Scholar]
  • 40.Zelko IN, Mariani TJ, Folz RJ. Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free radical biology & medicine. 2002;33(3):337–349. doi: 10.1016/s0891-5849(02)00905-x. [DOI] [PubMed] [Google Scholar]
  • 41.Nakao C, Ookawara T, Sato Y, Kizaki T, Imazeki N, Matsubara O, et al. Extracellular superoxide dismutase in tissues from obese (ob/ob) mice. Free radical research. 2000;33(3):229–241. doi: 10.1080/10715760000301401. [DOI] [PubMed] [Google Scholar]
  • 42.Adachi T, Inoue M, Hara H, Maehata E, Suzuki S. Relationship of plasma extracellular-superoxide dismutase level with insulin resistance in type 2 diabetic patients. The Journal of endocrinology. 2004;181(3):413–417. doi: 10.1677/joe.0.1810413. [DOI] [PubMed] [Google Scholar]

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