Table of Contents Author Guidelines Submit a Manuscript
Disease Markers
Volume 2018, Article ID 3061974, 16 pages
https://doi.org/10.1155/2018/3061974
Review Article

Association between MnSOD Val16Ala Polymorphism and Cancer Risk: Evidence from 33,098 Cases and 37,831 Controls

1Department of Biochemistry and Molecular Biology, Medical College, Henan University of Science and Technology, Luoyang, Henan 471023, China
2School of Materials Science and Engineering, Henan University of Science and Technology, Luoyang, Henan 471023, China

Correspondence should be addressed to Ping Wang; moc.361@gnipgnawyrolg and Sanqiang Li; moc.361@1002ilgnaiqnas

Received 14 March 2018; Accepted 25 July 2018; Published 2 September 2018

Academic Editor: Roberta Rizzo

Copyright © 2018 Ping Wang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Manganese superoxide dismutase (MnSOD) plays a critical role in the defense against reactive oxygen species. The association between MnSOD Val16Ala polymorphism and cancer risk has been widely studied, but the results are contradictory. To obtain more precision on the association, we performed the current meta-analysis with 33,098 cases and 37,831 controls from 88 studies retrieved from PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of association. We found that the polymorphism was associated with an increased overall cancer risk (homozygous: , 95% CI = 1.00–1.19; heterozygous: , 95% CI = 1.02–1.12; dominant: , 95% CI = 1.02–1.14; and allele comparison: , 95% CI = 1.02–1.11). Stratification analysis further showed an increased risk for prostate cancer, Asians, Caucasians, population-based studies, hospital-based studies, low quality and high quality studies. However, the increased risk for MnSOD Val16Ala polymorphism among Asians needs further validation based on the false-positive report probability (FPRP) test. To summarize, this meta-analysis suggests that the MnSOD Val16Ala polymorphism is associated with significantly increased cancer risk, which needs further validation in single large studies.

1. Introduction

Cancer is one of the leading causes of death across the world, with an estimate of over 20 million new cancer cases that will occur per year as early as 2025 [1]. Although great efforts have been devoted to cancer treatment, cancer still poses a huge threat to human health. Carcinogenesis is rather complex, and mounting evidence suggests that reactive oxygen species- (ROS-) related oxidative damage is involved in this process [24].

Among the endogenous antioxidants, manganese superoxide dismutase (MnSOD) is one of the critical enzymes which defends against ROS in the mitochondria. The MnSOD gene, located on chromosome 6q25.3, is composed of four introns and five extrons. Currently, several single-nucleotide polymorphisms (SNPs) in the MnSOD gene have been reported, of which the most extensively studied one is Val16Ala. Since this residue is 9 amino acids upstream of the cleavage site, it has also been called Val9Ala (rs4880) polymorphism [5]. A previous study has shown that Ala-MnSOD allowed more efficient MnSOD localized to the mitochondria than the Val-variant form [6]. In view of this, it is speculated that the Val form of MnSOD may be associated with higher levels of ROS and increased susceptibility to cancer.

Several studies have found the associations between the Val form of the MnSOD gene and increased cancer risk [79], but a majority of studies showed the Ala form to be associated with higher cancer risk, such as breast cancer [10, 11], esophageal cancer [12], colorectal cancer [13], and cervical cancer [14], and some other studies find no significant association between this polymorphism and cancer risk [1518]. To draw a more comprehensive estimation of this possible association, we conducted the present meta-analysis to evaluate the relevance of this variant with susceptibility of cancer.

2. Materials and Methods

2.1. Search Strategy

We systematically searched the PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases for all related publications using the following keywords: “MnSOD or manganese superoxide dismutase,” “polymorphism or variant or variation,” and “cancer or carcinoma or tumor or neoplasm” (the last search was updated on February 22, 2018). Additional relevant studies were searched manually from the references or review articles about this topic. If studies had overlapped data, only the one with the most participants was included in this analysis.

2.2. Inclusion and Exclusion Criteria

The inclusion criteria were as follows: (1) case-control studies, (2) studies assessing the association between MnSOD Val16Ala polymorphism and cancer risk, (3) and provision of detailed data about genotype and allele distribution of the studied polymorphism. Studies were excluded if any of the following aspects existed: (1) duplicate publications, (2) review articles or meta-analyses, (3) not a case-control study, and (4) genotype frequencies in the control departure from Hardy-Weinberg equilibrium (HWE).

2.3. Data Extraction

Two authors (Ping Wang and Yanfeng Zhu) independently extracted the data from included studies according to the criteria mentioned above. Disagreement was resolved by discussion until a consensus was reached. The following information was collected from each study: first author’s surname, year of publication, country of origin, ethnicity, cancer type, control source (hospital-based or population-based), genotyping methods, and numbers of cases and controls with the Val/Val, Val/Ala, and Ala/Ala genotypes.

2.4. Quality Assessment

The quality of each included study was assessed independently by two authors using the criteria from a previous study [19]. Quality scores were rated from 0 to 15, and the studies were classified as high-quality studies () and low-quality studies ().

2.5. Statistical Analysis

The strength of association between the MnSOD Val16Ala polymorphism and cancer risk was assessed by calculating the odd ratios (ORs) with the corresponding 95% confidence intervals (CIs). The pooled ORs of five comparison models were calculated: homozygous model (Ala/Ala versus Val/Val), heterozygous model (Val/Ala versus Val/Val), recessive model [Ala/Ala versus (Val/Val + Val/Ala)], dominant model [(Ala/Ala + Val/Ala) versus Val/Val], and an allele comparison (Ala versus Val). We used the chi-square-based test to check the between-study heterogeneity, and the fixed-effects model (the Mantel-Haenszel method) [20] was used when no significant heterogeneity was found (). Otherwise, the random-effects model (the Dersimonian and Laird method) [21] was applied. The stratification analysis was performed by cancer type (cancer types with less than three studies would be merged into the “others” group), ethnicity (Asians, Caucasians, Africans, or mixed which contained more than one ethnic group), control source (hospital-based studies and population-based studies), and quality scores (≤9 and >9). Publication bias was examined using Begg’s funnel plot [22] and Egger’s linear regression test [23]. Sensitivity analysis was carried out to assess the results stability by excluding one study each time and revaluating the pooled ORs and 95% CIs.

The false-positive report probability (FPRP) was calculated for all the significant findings in the present study. We set 0.2 as a FPRP threshold and assign a prior probability of 0.1 to detect an OR of 0.67/1.50 (protective/risk effects) for an association with the genotypes under investigation [24, 25]. FPRP values less than 0.2 were considered as noteworthy associations. All the statistical tests were performed with STATA software (version 12.0; Stata Corporation, College Station, TX). Two-sided values <0.05 were considered statistically significant.

3. Results

3.1. Study Characteristics

As shown in Figure 1, a total of 348 articles were identified from PubMed, Embase, CNKI, and Wanfang databases, and 34 more articles were identified by reading the references of retrieved publications. After reading the titles and abstracts, 266 articles were excluded, leaving 116 articles for further assessment. Among them, six were excluded as case-only studies [2631], five [3236] were covered by other included publications [7, 37, 38], three were without detailed data for further analysis [3941], and 18 deviated from HWE [4259]. Finally, a total of 84 case-control publications [718, 37, 38, 60129] were included in this meta-analysis. Of the 84 publications, three publications [37, 69, 82] with two ethnic groups were considered as two independent studies and one publication [119] with two cancer types were also considered as two independent studies.

Figure 1: Flowchart of included studies for the association between MnSOD Val16Ala polymorphism and cancer susceptibility.

For the two studies in the publication [119] with the same control group, the number of control was only calculated once in the total number. Overall, 88 studies with 33,098 cases and 37,831 controls were included in this meta-analysis. Of the 88 studies, 24 studies focused on breast cancer [911, 16, 38, 60, 61, 68, 69, 71, 72, 77, 88, 93, 96, 97, 100, 105, 109, 114, 119, 122, 127]; 17 on prostate cancer [37, 66, 74, 79, 82, 85, 86, 89, 95, 106, 111, 113, 120, 125, 128]; six for each of the following cancer types, such as lung cancer [7, 17, 18, 65, 92, 118], bladder cancer [8, 15, 67, 75, 112, 117], and pancreatic cancer [64, 91, 102, 107, 108, 121]; five on colorectal cancer [13, 63, 73, 94, 101]; three for each of the following cancer types, such as ovarian cancer [70, 81, 87], hepatocellular carcinoma [98, 99, 129], and non-Hodgkin’s lymphoma [76, 78, 110]; and the other with fewer than three studies for each cancer type. Of all the studies, 56 studies were performed on Caucasians, 18 studies on Asians, and seven studies on Africans and mixed ethnicity, respectively. When classified by source of control, 48 were population-based and 40 were hospital-based. In addition, according to the quality score, 49 studies were considered as high-quality and 39 studies were considered as low-quality. The characteristics of the included studies are shown in Table 1.

Table 1: Characteristics of studies included in the meta-analysis.
3.2. Meta-Analysis Results

The overall results suggested there was a significant association between MnSOD Val16Ala polymorphism and cancer risk (homozygous: , 95% CI = 1.00–1.19, ; heterozygous: , 95% CI = 1.02–1.12, ; dominant: , 95% CI = 1.02–1.14, ; and allele comparison: , 95% CI = 1.02–1.11, ) (Table 2, Figure 2). In the subgroup analysis, a statistically significant association was found for prostate cancer (heterozygous: , 95% CI = 1.05–1.24, ; dominant: , 95% CI = 1.05–1.23, ; and allele comparison: , 95% CI = 1.00–1.15, ), Asians (homozygous: , 95% CI = 1.15–2.88, , and recessive: , 95% CI = 1.16–2.68, ), Caucasians (heterozygous: , 95% CI = 1.03–1.13, ; dominant: , 95% CI = 1.02–1.14, ; and allele comparison: , 95% CI = 1.00–1.09, ), population-based studies (homozygous: , 95% CI = 1.01–1.19, ; heterozygous: , 95% CI = 1.02–1.12, ; dominant: , 95% CI = 1.02–1.13, ; and allele comparison: , 95% CI = 1.00–1.08, ), hospital-based studies (recessive: , 95% CI = 1.01–1.34, , and allele comparison: , 95% CI = 1.03–1.24, ), low-quality studies (allele comparison: , 95% CI = 1.02–1.23, ) and high-quality studies (homozygous: , 95% CI = 1.00–1.17, ; heterozygous: , 95% CI = 1.02–1.13, ; dominant: , 95% CI = 1.02–1.14, ; and allele comparison: , 95% CI = 1.00–1.09, ).

Table 2: Meta-analysis of the association between MnSOD Val16Ala polymorphism and cancer risk.
Figure 2: Forest plot of overall cancer risk associated with MnSOD Val16Ala polymorphism by dominant model. For each study, the estimated of OR and its 95% CI are plotted with a box and a horizontal line. ◇, pooled ORs and its 95% CIs.
3.3. Heterogeneity and Sensitivity Analysis

As shown in Table 2, substantial heterogeneities were found among all studies for the MnSOD Val16Ala polymorphism and overall cancer risk (homozygous: ; heterozygous: ; recessive: ; dominant: ; and allele comparison: ). Therefore, the random-effects model was used to generate wider CIs. The leave-one-out sensitivity analysis indicated that no single study could change the pooled ORs obviously (data not shown).

3.4. Publication Bias

Begg’s funnel plot and Egger’s test were performed to evaluate the publication bias of 88 studies, and we found significant publication bias for the homozygous model (), recessive model (), dominant model (), and allele comparison (), but not for the heterozygous model (). Therefore, the Duval and Tweedie nonparametric “trim and fill” method was used to adjust for publication bias. The “trim and fill” method did not draw different conclusions (data not shown), indicating that our findings were statistically robust.

3.5. False-Positive Report Probability (FPRP) Analysis

The FPRP values were calculated for all the significant findings (Table 3). With the assumption of a prior probability of 0.1, the FPRP results revealed that three genetic models [Val/Ala versus Val/Val, (Ala/Ala + Val/Ala) versus Val/Val, and Ala versus Val] of the MnSOD Val16Ala polymorphism were truly associated with increased cancer risk (, 0.045, and 0.106, resp.). In addition, according to the FPRP results, we confirmed that the MnSOD Val16Ala polymorphism was associated with cancer risk for prostate cancer (heterozygous: FPRP = 0.020 and dominant: FPRP = 0.006), Caucasians (heterozygous: FPRP = 0.008 and dominant: FPRP = 0.045), population-based studies (homozygous: FPRP = 0.136, heterozygous: FPRP = 0.032 and dominant: FPRP = 0.119), hospital-based studies (allele comparison: FPRP = 0.082), low-quality studies (allele comparison: FPRP = 0.138), and high-quality studies (heterozygous: FPRP = 0.119).

Table 3: False-positive report probability values for associations between cancer risk and MnSOD Val16Ala polymorphism.

4. Discussion

In this meta-analysis, we comprehensively assessed the association between MnSOD Val16Ala polymorphism and cancer risk through 88 studies, and we found that this gene polymorphism was significantly associated with overall cancer risk. Further, stratification analysis revealed that the association was more obvious for risk of prostate cancer, Asians, Caucasians, population-based studies, hospital-based studies, low-quality studies, and high-quality studies. To avoid the false-positive results of the meta-analysis, we performed the FPRP analysis for the significant findings by setting as the prior probability of 0.1, and the results suggested that the association between MnSOD Val16Ala polymorphism and cancer risk for Asians was false positive, which may due to limited sample size.

MnSOD is a mitochondrial enzyme that converts superoxide radical O2 into H2O2, and it plays a critical role in human cells. Studies have revealed that the aberrant expression of MnSOD is involved in many types of cancers. Our current study indicated that the MnSOD Val16Ala polymorphism was significantly associated with an increased overall cancer risk. Previous meta-analyses have also assessed the association of MnSOD Val16Ala polymorphism with cancer susceptibility. The study carried out by Kang [130] analyzed MnSOD Val16Ala polymorphism and cancer risk, consisting 52 studies with 26,865 cases and 32,464 controls, in which no significant association was found between this polymorphism and overall cancer risk. In the subgroup analysis, statistically significant associations were found between this polymorphism and non-Hodgkin lymphoma, lung cancer, and colorectal cancer. Another meta-analysis [131] including 7366 cases and 9102 controls found no overall association of MnSOD Val16Ala polymorphism for cancer risk. Some of the significant associations detected in the previous meta-analyses were not found in the present study; for example, MnSOD Val16Ala polymorphism was associated with the risk of hepatocellular carcinoma [132, 133], esophageal cancer [134], and lung cancer [134]. The discrepancy that occurred may be because our current study was based on a much larger sample size, allowing the more precise detection of the association. In the subgroup analysis by cancer type, we found a significant association between MnSOD Val16Ala polymorphism and elevated prostate cancer risk, and no significant association between this polymorphism and breast cancer, which were consistent with previous meta-analyses [131, 134137].

In spite of genetic importance, environment factors such as dietary pattern and exercise play important roles in the development of cancer. Recently, several studies have investigated the association between dietary intake of antioxidant-rich foods and MnSOD Val16Ala polymorphism in breast cancer [60], prostate cancer [89], and cervical cancer [14]. Despite the lack of consistent data, the results suggested that the MnSOD Val16Ala polymorphism and cancer risk could be modulated by dietary factors. Besides, a previous study had shown that moderate exercise training is beneficial for prostate cancer [138], and evidence showed that exercise training may result in positive MnSOD modulation through redox sensitive pathways [139].

The current meta-analysis has several advantages. First, we included the latest publications in the present study and also the publications written in Chinese. Second, the quality of included studies was assessed by the quality score criteria. Third, the FPRP test was performed to make the results more trustworthy and robust. Although the study is the largest and most comprehensive one regarding the association between MnSOD Val16Ala polymorphism and all cancer types, there were still some limitations that should be addressed. First, the number of cases in each study was small (<1000) in all but seven studies [11, 38, 69, 78, 82, 86, 119], which may have an effect on the investigation of the real association. Second, the results were based on unadjusted estimates, which might make the results imprecise. Third, only publications in English and Chinese were included, which could lead to selection bias. Fourth, in the subgroup analysis by cancer type, less than three studies were included for some types of cancer, which may affect the detection of the real association. Finally, the potential gene-gene, and gene-environment interactions were not investigated due to the lack of original information.

Despite of these limitations, this meta-analysis indicated there was a significant association between MnSOD Val16Ala polymorphism and cancer risk, which should be further validated by single large studies.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Acknowledgments

This work was supported by the Key Research Programs for Institutions of Higher Education in Henan Province (Grant no. 18A180012).

References

  1. J. Ferlay, I. Soerjomataram, R. Dikshit et al., “Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012,” International Journal of Cancer, vol. 136, no. 5, pp. E359–E386, 2015. View at Publisher · View at Google Scholar · View at Scopus
  2. D. Ziech, R. Franco, A. Pappa, and M. I. Panayiotidis, “Reactive oxygen species (ROS)––induced genetic and epigenetic alterations in human carcinogenesis,” Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, vol. 711, no. 1-2, pp. 167–173, 2011. View at Publisher · View at Google Scholar · View at Scopus
  3. G. Waris and H. Ahsan, “Reactive oxygen species: role in the development of cancer and various chronic conditions,” Journal of Carcinogenesis, vol. 5, no. 1, p. 14, 2006. View at Publisher · View at Google Scholar · View at Scopus
  4. J. M. Matés and F. M. Sánchez-Jiménez, “Role of reactive oxygen species in apoptosis: implications for cancer therapy,” The International Journal of Biochemistry & Cell Biology, vol. 32, no. 2, pp. 157–170, 2000. View at Publisher · View at Google Scholar · View at Scopus
  5. J. S. Rosenblum, N. B. Gilula, and R. A. Lerner, “On signal sequence polymorphisms and diseases of distribution,” Proceedings of the National Academy of Sciences, vol. 93, no. 9, pp. 4471–4473, 1996. View at Publisher · View at Google Scholar · View at Scopus
  6. A. Sutton, H. Khoury, C. Prip-Buus, C. Cepanec, D. Pessayre, and F. Degoul, “The Ala16Val genetic dimorphism modulates the import of human manganese superoxide dismutase into rat liver mitochondria,” Pharmacogenetics, vol. 13, no. 3, pp. 145–157, 2003. View at Publisher · View at Google Scholar · View at Scopus
  7. L. I. Wang, D. P. Miller, Y. Sai et al., “Manganese superoxide dismutase alanine-to-valine polymorphism at codon 16 and lung cancer risk,” Journal of the National Cancer Institute, vol. 93, no. 23, pp. 1818–1821, 2001. View at Publisher · View at Google Scholar · View at Scopus
  8. R. J. Hung, P. Boffetta, P. Brennan et al., “Genetic polymorphisms of MPO, COMT, MnSOD, NQO1, interactions with environmental exposures and bladder cancer risk,” Carcinogenesis, vol. 25, no. 6, pp. 973–978, 2004. View at Publisher · View at Google Scholar · View at Scopus
  9. M. Bergman, M. Ahnstrom, P. Palmeback Wegman, and S. Wingren, “Polymorphism in the manganese superoxide dismutase (MnSOD) gene and risk of breast cancer in young women,” Journal of Cancer Research and Clinical Oncology, vol. 131, no. 7, pp. 439–444, 2005. View at Publisher · View at Google Scholar · View at Scopus
  10. K. Mitrunen, P. Sillanpää, V. Kataja et al., “Association between manganese superoxide dismutase (MnSOD) gene polymorphism and breast cancer risk,” Carcinogenesis, vol. 22, no. 5, pp. 827–829, 2001. View at Publisher · View at Google Scholar
  11. Q. Cai, X. O. Shu, W. Wen et al., “Genetic polymorphism in the manganese superoxide dismutase gene, antioxidant intake, and breast cancer risk: results from the Shanghai Breast Cancer Study,” Breast Cancer Research, vol. 6, no. 6, pp. R647–R655, 2004. View at Publisher · View at Google Scholar · View at Scopus
  12. S. J. Murphy, A. E. Hughes, C. C. Patterson et al., “A population-based association study of SNPs of GSTP1, MnSOD, GPX2 and Barrett’s esophagus and esophageal adenocarcinoma,” Carcinogenesis, vol. 28, no. 6, pp. 1323–1328, 2007. View at Publisher · View at Google Scholar · View at Scopus
  13. J. Stoehlmacher, S. A. Ingles, D. J. Park, W. Zhang, and H. J. Lenz, “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, vol. 9, no. 2, pp. 235–238, 2002. View at Publisher · View at Google Scholar
  14. S. Y. Tong, J. M. Lee, E. S. Song et al., “Functional polymorphism in manganese superoxide dismutase and antioxidant status: their interactions on the risk of cervical intraepithelial neoplasia and cervical cancer,” Gynecologic Oncology, vol. 115, no. 2, pp. 272–276, 2009. View at Publisher · View at Google Scholar · View at Scopus
  15. M. Cengiz, A. Ozaydin, A. C. Ozkilic, and G. Dedekarginoglu, “The investıgatıon of GSTT1, GSTM1 and SOD polymorphism in bladder cancer patıents,” International Urology and Nephrology, vol. 39, no. 4, pp. 1043–1048, 2007. View at Publisher · View at Google Scholar · View at Scopus
  16. K. M. Egan, P. A. Thompson, L. Titus-Ernstoff, J. H. Moore, and C. B. Ambrosone, “MnSOD polymorphism and breast cancer in a population-based case–control study,” Cancer Letters, vol. 199, no. 1, pp. 27–33, 2003. View at Publisher · View at Google Scholar · View at Scopus
  17. Q. Lan, J. L. Mumford, M. Shen et al., “Oxidative damage-related genes AKR1C3 and OGG1 modulate risks for lung cancer due to exposure to PAH-rich coal combustion emissions,” Carcinogenesis, vol. 25, no. 11, pp. 2177–2181, 2004. View at Publisher · View at Google Scholar · View at Scopus
  18. J. C. Ho, J. C. Mak, S. P. Ho et al., “Manganese superoxide dismutase and catalase genetic polymorphisms, activity levels, and lung cancer risk in Chinese in Hong Kong,” Journal of Thoracic Oncology, vol. 1, no. 7, pp. 648–653, 2006. View at Publisher · View at Google Scholar
  19. J. He, X. Y. Liao, J. H. Zhu et al., “Association of MTHFR C677T and A1298C polymorphisms with non-Hodgkin lymphoma susceptibility: evidence from a meta-analysis,” Scientific Reports, vol. 4, no. 1, p. 6159, 2014. View at Publisher · View at Google Scholar · View at Scopus
  20. N. Mantel and W. Haenszel, “Statistical aspects of the analysis of data from retrospective studies of disease,” Journal of the National Cancer Institute, vol. 22, no. 4, pp. 719–748, 1959. View at Publisher · View at Google Scholar · View at Scopus
  21. R. Dersimonian and N. Laird, “Meta-analysis in clinical trials,” Controlled Clinical Trials, vol. 7, no. 3, pp. 177–188, 1986. View at Publisher · View at Google Scholar · View at Scopus
  22. C. B. Begg and M. Mazumdar, “Operating characteristics of a rank correlation test for publication bias,” Biometrics, vol. 50, no. 4, pp. 1088–1101, 1994. View at Publisher · View at Google Scholar · View at Scopus
  23. M. Egger, G. D. Smith, M. Schneider, and C. Minder, “Bias in meta-analysis detected by a simple, graphical test,” British Medical Journal, vol. 315, no. 7109, pp. 629–634, 1997. View at Publisher · View at Google Scholar
  24. S. Wacholder, S. Chanock, M. Garcia-Closas, L. el ghormli, and N. Rothman, “Assessing the probability that a positive report is false: an approach for molecular epidemiology studies,” Journal of the National Cancer Institute, vol. 96, no. 6, pp. 434–442, 2004. View at Publisher · View at Google Scholar · View at Scopus
  25. J. He, M. Y. Wang, L. X. Qiu et al., “Genetic variations of mTORC1 genes and risk of gastric cancer in an eastern chinese population,” Molecular Carcinogenesis, vol. 52, no. S1, pp. 70–79, 2013. View at Publisher · View at Google Scholar · View at Scopus
  26. J. Ahn, C. B. Ambrosone, P. A. Kanetsky et al., “Polymorphisms in genes related to oxidative stress (CAT, MnSOD, MPO, and eNOS) and acute toxicities from radiation therapy following lumpectomy for breast cancer,” Clinical Cancer Research, vol. 12, no. 23, pp. 7063–7070, 2006. View at Publisher · View at Google Scholar · View at Scopus
  27. T. Iguchi, C. Y. Wang, N. B. Delongchamps et al., “Association of prostate cancer and manganese superoxide dismutase AA genotype influenced by presence of occult cancer in control group,” Urology, vol. 72, no. 2, pp. 238–241, 2008. View at Publisher · View at Google Scholar · View at Scopus
  28. Y. J. Cheng, Y. D. Wang, Q. Liu, J. Zhang, and X. Wan, “Influence of MnSOD gene polymorphism on the curative effect of radiotherapy in esophageal squamous cell carcinoma,” Carcinogenesis, Teratogenesis & Mutagenesis, vol. 23, pp. 9–12, 2011. View at Google Scholar
  29. P. J. Dluzniewski, M. H. Wang, S. L. Zheng et al., “Variation in IL10 and other genes involved in the immune response and in oxidation and prostate cancer recurrence,” Cancer Epidemiology Biomarkers & Prevention, vol. 21, no. 10, pp. 1774–1782, 2012. View at Publisher · View at Google Scholar · View at Scopus
  30. J. E. Megías, P. Montesinos, M. J. Herrero et al., “Prognostic impact of anthracycline metabolism gene polymorphisms in newly diagnosed acute myeloid leukemia adults,” Blood, vol. 124, no. 21, p. 2237, 2014. View at Google Scholar
  31. T. Iguchi, C. Y. Wang, N. B. Delongchamps et al., “Association of MnSOD AA genotype with the progression of prostate cancer,” PLoS One, vol. 10, no. 7, article e0131325, 2015. View at Publisher · View at Google Scholar · View at Scopus
  32. L. I. Wang, D. Neuberg, and D. C. Christiani, “Asbestos exposure, manganese superoxide dismutase (MnSOD) genotype, and lung cancer risk,” Journal of Occupational and Environmental Medicine, vol. 46, no. 6, pp. 556–564, 2004. View at Publisher · View at Google Scholar · View at Scopus
  33. G. Liu, W. Zhou, S. Park et al., “The SOD2 Val/Val genotype enhances the risk of nonsmall cell lung carcinoma by p53 and XRCC1 polymorphisms,” Cancer, vol. 101, no. 12, pp. 2802–2808, 2004. View at Publisher · View at Google Scholar · View at Scopus
  34. G. Liu, W. Zhou, L. I. Wang et al., “MPO and SOD2 polymorphisms, gender, and the risk of non-small cell lung carcinoma,” Cancer Letters, vol. 214, no. 1, pp. 69–79, 2004. View at Publisher · View at Google Scholar · View at Scopus
  35. J. Y. Choi, M. L. Neuhouser, M. J. Barnett et al., “Iron intake, oxidative stress-related genes (MnSOD and MPO) and prostate cancer risk in CARET cohort,” Carcinogenesis, vol. 29, no. 5, pp. 964–970, 2008. View at Publisher · View at Google Scholar · View at Scopus
  36. L. E. McCullough, M. D. Gammon, R. J. Cleveland et al., “Abstract 2601: polymorphisms in oxidative stress genes, physical activity and breast cancer risk,” Cancer Research, vol. 72, Supplement, no. 8, p. 2601, 2012. View at Publisher · View at Google Scholar
  37. J. Y. Choi, M. L. Neuhouser, M. Barnett et al., “Polymorphisms in oxidative stress–related genes are not associated with prostate cancer risk in heavy smokers,” Cancer Epidemiology Biomarkers & Prevention, vol. 16, no. 6, pp. 1115–1120, 2007. View at Publisher · View at Google Scholar · View at Scopus
  38. M. M. Gaudet, M. D. Gammon, R. M. Santella et al., “MnSOD Val-9Ala genotype, pro- and anti-oxidant environmental modifiers, and breast cancer among women on Long Island, New York,” Cancer Causes & Control, vol. 16, no. 10, pp. 1225–1234, 2005. View at Publisher · View at Google Scholar · View at Scopus
  39. D. G. Cox, R. M. Tamimi, and D. J. Hunter, “Gene × gene interaction between MnSOD and GPX-1 and breast cancer risk: a nested case-control study,” BMC Cancer, vol. 6, no. 1, p. 217, 2006. View at Publisher · View at Google Scholar · View at Scopus
  40. M. Manuguerra, G. Matullo, F. Veglia et al., “Multi-factor dimensionality reduction applied to a large prospective investigation on gene–gene and gene–environment interactions,” Carcinogenesis, vol. 28, no. 2, pp. 414–422, 2007. View at Publisher · View at Google Scholar · View at Scopus
  41. P. Vineis, F. Veglia, S. Garte et al., “Genetic susceptibility according to three metabolic pathways in cancers of the lung and bladder and in myeloid leukemias in nonsmokers,” Annals of Oncology, vol. 18, no. 7, pp. 1230–1242, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. B. Yu, C. L. Yan, and K. H. Liao, “Study on the relationship between skin cancer and the genetic polymorphism in the signal sequence of the manganese superoxide dismutase (MnSOD),” Journal of Clinical Dermatology, vol. 30, pp. 227–229, 2001. View at Google Scholar
  43. N. A. Kocabaş, S. Şardaş, S. Cholerton, A. K. Daly, A. H. Elhan, and A. E. Karakaya, “Genetic polymorphism of manganese superoxide dismutase (MnSOD) and breast cancer susceptibility,” Cell Biochemistry & Function, vol. 23, no. 1, pp. 73–76, 2005. View at Publisher · View at Google Scholar · View at Scopus
  44. R. C. G. Martin, Q. Lan, K. Hughes et al., “No apparent association between genetic polymorphisms (−102 C>T) and (−9 T>C) in the human manganese superoxide dismutase gene and gastric cancer,” Journal of Surgical Research, vol. 124, no. 1, pp. 92–97, 2005. View at Publisher · View at Google Scholar · View at Scopus
  45. M. Taufer, A. Peres, V. M. de Andrade et al., “Is the Val16Ala manganese superoxide dismutase polymorphism associated with the aging process?” The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, vol. 60, no. 4, pp. 432–438, 2005. View at Publisher · View at Google Scholar
  46. S. N. Silva, M. N. Cabral, G. Bezerra de Castro et al., “Breast cancer risk and polymorphisms in genes involved in metabolism of estrogens (CYP17, HSD17β1, COMT and MnSOD): possible protective role of MnSOD gene polymorphism Val/Ala and Ala/Ala in women that never breast fed,” Oncology Reports, vol. 16, no. 4, pp. 781–788, 2006. View at Publisher · View at Google Scholar
  47. C. G. Bica, I. B. M. da Cruz, L. L. de Moura da Silva, N. V. Toscani, C. G. Zettler, and M. S. Graudenz, “Association of manganese superoxide dismutase gene polymorphism (Ala-9Val) and breast cancer in males and females,” Jornal Brasileiro de Patologia e Medicina Laboratorial, vol. 43, no. 3, pp. 219–225, 2007. View at Publisher · View at Google Scholar · View at Scopus
  48. C. G. Bica, L. L. de Moura da Silva, N. V. Toscani et al., “MnSOD gene polymorphism association with steroid-dependent cancer,” Pathology & Oncology Research, vol. 15, no. 1, pp. 19–24, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. Y. J. Cheng, Y. D. Wang, Q. Liu et al., “Association of single nucleotide polymorphism of MnSOD gene with carcinogenesis and development of esophageal squamous cell carcinoma,” Chinese Journal of Oncology, vol. 31, no. 11, pp. 831–835, 2009. View at Publisher · View at Google Scholar
  50. L. Sun, I. R. Konig, and N. Homann, “Manganese superoxide dismutase (MnSOD) polymorphism, alcohol, cigarette smoking and risk of oesophageal cancer,” Alcohol and Alcoholism, vol. 44, no. 4, pp. 353–357, 2009. View at Publisher · View at Google Scholar · View at Scopus
  51. J. Zejnilovic, N. Akev, H. Yilmaz, and T. Isbir, “Association between manganese superoxide dismutase polymorphism and risk of lung cancer,” Cancer Genetics and Cytogenetics, vol. 189, no. 1, pp. 1–4, 2009. View at Publisher · View at Google Scholar · View at Scopus
  52. C. G. Bica, L. L. de Moura da Silva, N. V. Toscani et al., “Polymorphism (ALA16VAL) correlates with regional lymph node status in breast cancer,” Cancer Genetics and Cytogenetics, vol. 196, no. 2, pp. 153–158, 2010. View at Publisher · View at Google Scholar · View at Scopus
  53. G. Aynali, M. Doğan, R. Sütcü et al., “Polymorphic variants of MnSOD Val16Ala, CAT-262 C < T and GPx1 Pro198Leu genotypes and the risk of laryngeal cancer in a smoking population,” The Journal of Laryngology & Otology, vol. 127, no. 10, pp. 997–1000, 2013. View at Publisher · View at Google Scholar · View at Scopus
  54. C. Bănescu, A. P. Trifa, S. Voidăzan et al., “CAT, GPX1, MnSOD, GSTM1, GSTT1, and GSTP1 genetic polymorphisms in chronic myeloid leukemia: a case-control study,” Oxidative Medicine and Cellular Longevity, vol. 2014, Article ID 875861, 6 pages, 2014. View at Publisher · View at Google Scholar · View at Scopus
  55. D. Goerlitz, S. Amr, C. Dash et al., “Genetic polymorphisms in NQO1 and SOD2: interactions with smoking, schistosoma infection, and bladder cancer risk in Egypt,” Urologic Oncology: Seminars and Original Investigations, vol. 32, no. 1, pp. 47.e15–47.e20, 2014. View at Publisher · View at Google Scholar · View at Scopus
  56. E. Reszka, Z. Jablonowski, E. Wieczorek et al., “Polymorphisms of NRF2 and NRF2 target genes in urinary bladder cancer patients,” Journal of Cancer Research and Clinical Oncology, vol. 140, no. 10, pp. 1723–1731, 2014. View at Publisher · View at Google Scholar · View at Scopus
  57. M. T. Moradi, K. Yari, Z. Rahimi, E. Kazemi, and M. Shahbazi, “Manganese superoxide dismutase (MnSOD Val-9Ala) gene polymorphism and susceptibility to gastric cancer,” Asian Pacific Journal of Cancer Prevention, vol. 16, no. 2, pp. 485–488, 2015. View at Publisher · View at Google Scholar · View at Scopus
  58. C. Zhang, L. Guo, Y. Qin, and L. Qin, “Interaction between single nucleotide polymorphism of manganese superoxide dismutase gene C1183T, resistin gene promoter-420C/G and cigarette smoking in esophageal squamous cell carcinoma,” Shanghai Medical Journal, vol. 38, no. 11, pp. 828–834, 2015. View at Google Scholar
  59. C. Bănescu, M. Iancu, A. P. Trifa et al., “From six gene polymorphisms of the antioxidant system, only GPX Pro198Leu and GSTP1 Ile105Val modulate the risk of acute myeloid leukemia,” Oxidative Medicine and Cellular Longevity, vol. 2016, Article ID 2536705, 10 pages, 2016. View at Publisher · View at Google Scholar · View at Scopus
  60. C. B. Ambrosone, J. L. Freudenheim, P. A. Thompson et al., “Manganese superoxide dismutase (MnSOD) genetic polymorphisms, dietary antioxidants, and risk of breast cancer,” Cancer Research, vol. 59, no. 3, pp. 602–606, 1999. View at Google Scholar
  61. H. Green, G. Ross, J. Peacock, R. Owen, J. Yarnold, and R. Houlston, “Variation in the manganese superoxide dismutase gene (SOD2) is not a major cause of radiotherapy complications in breast cancer patients,” Radiotherapy and Oncology, vol. 63, no. 2, pp. 213–216, 2002. View at Publisher · View at Google Scholar · View at Scopus
  62. A. Hirvonen, J. Tuimala, T. Ollikainen, K. Linnainmaa, and V. Kinnula, “Manganese superoxide dismutase genotypes and asbestos-associated pulmonary disorders,” Cancer Letters, vol. 178, no. 1, pp. 71–74, 2002. View at Publisher · View at Google Scholar · View at Scopus
  63. A. J. Levine, E. Elkhouly, A. T. Diep, E. R. Lee, H. Frankl, and R. W. Haile, “The MnSOD A16V mitochondrial targeting sequence polymorphism is not associated with increased risk of distal colorectal adenomas: data from a sigmoidoscopy-based case control study,” Cancer Epidemiology Biomarkers & Prevention, vol. 11, pp. 1140-1141, 2002. View at Google Scholar
  64. D. Li, P. F. Firozi, W. Zhang et al., “DNA adducts, genetic polymorphisms, and K-ras mutation in human pancreatic cancer,” Mutation Research/Genetic Toxicology and Environmental Mutagenesis, vol. 513, no. 1-2, pp. 37–48, 2002. View at Publisher · View at Google Scholar · View at Scopus
  65. P. Lin, Y. M. Hsueh, J. L. Ko, Y. F. Liang, K. J. Tsai, and C. Y. Chen, “Analysis of NQO1, GSTP1, and MnSOD genetic polymorphisms on lung cancer risk in Taiwan,” Lung Cancer, vol. 40, no. 2, pp. 123–129, 2003. View at Publisher · View at Google Scholar · View at Scopus
  66. K. Woodson, J. A. Tangrea, T. A. Lehman et al., “Manganese superoxide dismutase (MnSOD) polymorphism, α-tocopherol supplementation and prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (Finland),” Cancer Causes & Control, vol. 14, no. 6, pp. 513–518, 2003. View at Publisher · View at Google Scholar · View at Scopus
  67. Y. Ichimura, T. Habuchi, N. Tsuchiya et al., “Increased risk of bladder cancer associated with a glutathione peroxidase 1 codon 198 variant,” The Journal of Urology, vol. 172, no. 2, pp. 728–732, 2004. View at Publisher · View at Google Scholar · View at Scopus
  68. J. A. Knight, U. V. Onay, S. Wells et al., “Genetic variants of GPX1 and SOD2 and breast cancer risk at the Ontario site of the Breast Cancer Family Registry,” Cancer Epidemiology Biomarkers & Prevention, vol. 13, no. 1, pp. 146–149, 2004. View at Publisher · View at Google Scholar · View at Scopus
  69. R. C. Millikan, J. Player, A. R. de Cotret et al., “Manganese superoxide dismutase Ala-9Val polymorphism and risk of breast cancer in a population-based case–control study of African Americans and whites,” Breast Cancer Research, vol. 6, no. 4, pp. R264–R274, 2004. View at Publisher · View at Google Scholar
  70. S. Olson, M. Carlson, H. Ostrer et al., “Genetic variants in SOD2, MPO, and NQO1, and risk of ovarian cancer,” Gynecologic Oncology, vol. 93, no. 3, pp. 615–620, 2004. View at Publisher · View at Google Scholar · View at Scopus
  71. R. M. Tamimi, S. E. Hankinson, D. Spiegelman, G. A. Colditz, and D. J. Hunter, “Manganese superoxide dismutase polymorphism, plasma antioxidants, cigarette smoking, and risk of breast cancer,” Cancer Epidemiology Biomarkers & Prevention, vol. 13, pp. 989–996, 2004. View at Google Scholar
  72. T. C. Cheng, S. T. Chen, C. S. Huang et al., “Breast cancer risk associated with genotype polymorphism of the catechol estrogen-metabolizing genes: a multigenic study on cancer susceptibility,” International Journal of Cancer, vol. 113, no. 3, pp. 345–353, 2005. View at Publisher · View at Google Scholar · View at Scopus
  73. S. Landi, F. Gemignani, V. Moreno et al., “A comprehensive analysis of phase I and phase II metabolism gene polymorphisms and risk of colorectal cancer,” Pharmacogenetics and Genomics, vol. 15, no. 8, pp. 535–546, 2005. View at Publisher · View at Google Scholar · View at Scopus
  74. H. Li, P. W. Kantoff, E. Giovannucci et al., “Manganese superoxide dismutase polymorphism, prediagnostic antioxidant status, and risk of clinical significant prostate cancer,” Cancer Research, vol. 65, no. 6, pp. 2498–2504, 2005. View at Publisher · View at Google Scholar · View at Scopus
  75. P. D. Terry, D. M. Umbach, and J. A. Taylor, “No association between SOD2 or NQO1 genotypes and risk of bladder cancer,” Cancer Epidemiology Biomarkers & Prevention, vol. 14, no. 3, pp. 753-754, 2005. View at Publisher · View at Google Scholar · View at Scopus
  76. T. J. Lightfoot, C. F. Skibola, A. G. Smith et al., “Polymorphisms in the oxidative stress genes, superoxide dismutase, glutathione peroxidase and catalase and risk of non-Hodgkin’s lymphoma,” Haematologica, vol. 91, no. 9, pp. 1222–1227, 2006. View at Google Scholar
  77. T. E. Slanger, J. Chang-Claude, and S. Wang-Gohrke, “Manganese superoxide dismutase Ala-9Val polymorphism, environmental modifiers, and risk of breast cancer in a German population,” Cancer Causes & Control, vol. 17, no. 8, pp. 1025–1031, 2006. View at Publisher · View at Google Scholar · View at Scopus
  78. S. S. Wang, S. Davis, J. R. Cerhan et al., “Polymorphisms in oxidative stress genes and risk for non-Hodgkin lymphoma,” Carcinogenesis, vol. 27, no. 9, pp. 1828–1834, 2006. View at Publisher · View at Google Scholar · View at Scopus
  79. H. Ergen, F. Narter, Ö. Timirci, and T. Isbir, “Effects of manganase superoxide dismutase Ala-9Val polymorphism on prostate cancer: a case-control study,” Anticancer Research, vol. 27, no. 2, pp. 1227–1230, 2007. View at Google Scholar
  80. J. Han, G. A. Colditz, and D. J. Hunter, “Manganese superoxide dismutase polymorphism and risk of skin cancer (United States),” Cancer Causes & Control, vol. 18, no. 1, pp. 79–89, 2007. View at Publisher · View at Google Scholar · View at Scopus
  81. S. E. Johnatty, C. M. Nagle, A. B. Spurdle et al., “The MnSOD Val9Ala polymorphism, dietary antioxidant intake, risk and survival in ovarian cancer (Australia),” Gynecologic Oncology, vol. 107, no. 3, pp. 388–391, 2007. View at Publisher · View at Google Scholar · View at Scopus
  82. D. Kang, K. M. Lee, S. K. Park 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, vol. 16, no. 8, pp. 1581–1586, 2007. View at Publisher · View at Google Scholar · View at Scopus
  83. S. Landi, F. Gemignani, M. Neri et al., “Polymorphisms of glutathione-S-transferase M1 and manganese superoxide dismutase are associated with the risk of malignant pleural mesothelioma,” International Journal of Cancer, vol. 120, no. 12, pp. 2739–2743, 2007. View at Publisher · View at Google Scholar · View at Scopus
  84. E. di Martino, L. J. Hardie, C. P. Wild et al., “The NAD(P)H:quinone oxidoreductase I C609T polymorphism modifies the risk of Barrett esophagus and esophageal adenocarcinoma,” Genetics in Medicine, vol. 9, no. 6, pp. 341–347, 2007. View at Publisher · View at Google Scholar · View at Scopus
  85. Z. Arsova-Sarafinovska, N. Matevska, D. Petrovski et al., “Manganese superoxide dismutase (MnSOD) genetic polymorphism is associated with risk of early-onset prostate cancer,” Cell Biochemistry & Function, vol. 26, no. 7, pp. 771–777, 2008. View at Publisher · View at Google Scholar
  86. M. L. Cooper, H. O. Adami, H. Grönberg, F. Wiklund, F. R. Green, and M. P. Rayman, “Interaction between single nucleotide polymorphisms in selenoprotein P and mitochondrial superoxide dismutase determines prostate cancer risk,” Cancer Research, vol. 68, no. 24, pp. 10171–10177, 2008. View at Publisher · View at Google Scholar · View at Scopus
  87. A. B. Dalan, A. Ergen, H. Yılmaz, A. Karateke, and T. İsbir, “Manganese superoxide dismutase gene polymorphism, MnSOD plasma levels and risk of epithelial ovarian cancer,” Journal of Obstetrics and Gynaecology Research, vol. 34, no. 5, pp. 878–884, 2008. View at Publisher · View at Google Scholar · View at Scopus
  88. C. Justenhoven, U. Hamann, F. Schubert et al., “Breast cancer: a candidate gene approach across the estrogen metabolic pathway,” Breast Cancer Research and Treatment, vol. 108, no. 1, pp. 137–149, 2008. View at Publisher · View at Google Scholar · View at Scopus
  89. B. Mikhak, D. J. Hunter, D. Spiegelman et al., “Manganese superoxide dismutase (MnSOD) gene polymorphism, interactions with carotenoid levels and prostate cancer risk,” Carcinogenesis, vol. 29, no. 12, pp. 2335–2340, 2008. View at Publisher · View at Google Scholar · View at Scopus
  90. P. Rajaraman, A. Hutchinson, N. Rothman et al., “Oxidative response gene polymorphisms and risk of adult brain tumors,” Neuro-Oncology, vol. 10, no. 5, pp. 709–715, 2008. View at Publisher · View at Google Scholar · View at Scopus
  91. P. Wheatley-Price, K. Asomaning, A. Reid et al., “Myeloperoxidase and superoxide dismutase polymorphisms are associated with an increased risk of developing pancreatic adenocarcinoma,” Cancer, vol. 112, no. 5, pp. 1037–1042, 2008. View at Publisher · View at Google Scholar · View at Scopus
  92. S. Zienolddiny, D. Campa, H. Lind 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, vol. 29, no. 6, pp. 1164–1169, 2008. View at Publisher · View at Google Scholar · View at Scopus
  93. N. Eras-Erdogan, E. Akbas, H. Senli, S. Kul, and T. Colak, “Relationship between polymorphism in the manganese superoxide dismutase gene and breast cancer,” Mutation Research/Genetic Toxicology and Environmental Mutagenesis, vol. 680, no. 1-2, pp. 7–11, 2009. View at Publisher · View at Google Scholar · View at Scopus
  94. S. Funke, M. Hoffmeister, H. Brenner, and J. Chang-Claude, “Effect modification by smoking on the association between genetic polymorphisms in oxidative stress genes and colorectal cancer risk,” Cancer Epidemiology Biomarkers & Prevention, vol. 18, no. 8, pp. 2336–2338, 2009. View at Publisher · View at Google Scholar · View at Scopus
  95. T. Iguchi, S. Sugita, C. Y. Wang, N. B. Newman, T. Nakatani, and G. P. Haas, “MnSOD genotype and prostate cancer risk as a function of NAT genotype and smoking status,” In Vivo, vol. 23, no. 1, pp. 7–12, 2009. View at Google Scholar
  96. N. A. Kostrykina, E. A. Pechkovskiy, U. A. Boyarskikh et al., “Associations of polymorphic variant of MnSOD gene with breast cancer in residents of the Altai region,” Bulletin of Experimental Biology and Medicine, vol. 147, no. 1, pp. 84–87, 2009. View at Publisher · View at Google Scholar · View at Scopus
  97. N. A. Ermolenko, U. A. Boyarskikh, A. G. Sushko et al., “Effect of point substitutions in the MnSOD, GPX1, and GSTP1 genes on the risk of familial and sporadic breast cancers in residents of Altai Krai,” Russian Journal of Genetics, vol. 46, no. 12, pp. 1486–1491, 2010. View at Publisher · View at Google Scholar · View at Scopus
  98. S. Ezzikouri, A. E. El Feydi, R. Afifi et al., “Polymorphisms in antioxidant defence genes and susceptibility to hepatocellular carcinoma in a Moroccan population,” Free Radical Research, vol. 44, no. 2, pp. 208–216, 2010. View at Publisher · View at Google Scholar · View at Scopus
  99. A. Ibrahim, S. A. El-Azim, and M. A. El-Azim, “Association of MnSOD Ala16Val genotype and activity with hepatocellular carcinoma risk in HCV-infected Egyptian patients,” Arab Journal of Gastroenterology, vol. 11, no. 1, pp. 19–23, 2010. View at Publisher · View at Google Scholar · View at Scopus
  100. M. K. Kim, S. H. Ahn, B. H. Son, and M. K. Sung, “Plasma antioxidant concentration, not superoxide dismutase polymorphism, is associated with breast cancer risk in Korean women,” Nutrition Research, vol. 30, no. 10, pp. 705–713, 2010. View at Publisher · View at Google Scholar · View at Scopus
  101. C. Méplan, D. J. Hughes, B. Pardini et al., “Genetic variants in selenoprotein genes increase risk of colorectal cancer,” Carcinogenesis, vol. 31, no. 6, pp. 1074–1079, 2010. View at Publisher · View at Google Scholar · View at Scopus
  102. H. Tang, X. Dong, R. S. Day, M. M. Hassan, and D. Li, “Antioxidant genes, diabetes and dietary antioxidants in association with risk of pancreatic cancer,” Carcinogenesis, vol. 31, no. 4, pp. 607–613, 2010. View at Publisher · View at Google Scholar · View at Scopus
  103. S. H. Wu, K. W. Lee, C. H. Chen et al., “Epistasis of oxidative stress-related enzyme genes on modulating the risks in oral cavity cancer,” Clinica Chimica Acta, vol. 411, no. 21-22, pp. 1705–1710, 2010. View at Publisher · View at Google Scholar · View at Scopus
  104. J. F. Yi, Y. M. Li, T. Liu et al., “Mn-SOD and CuZn-SOD polymorphisms and interactions with risk factors in gastric cancer,” World Journal of Gastroenterology, vol. 16, no. 37, pp. 4738–4746, 2010. View at Publisher · View at Google Scholar · View at Scopus
  105. J. Z. Cerne, M. Pohar-Perme, S. Novakovic, S. Frkovic-Grazio, V. Stegel, and K. Gersak, “Combined effect of CYP1B1, COMT, GSTP1, and MnSOD genotypes and risk of postmenopausal breast cancer,” Journal of Gynecologic Oncology, vol. 22, no. 2, pp. 110–119, 2011. View at Publisher · View at Google Scholar · View at Scopus
  106. T. Y. D. Cheng, M. J. Barnett, A. R. Kristal et al., “Genetic variation in myeloperoxidase modifies the association of serum α-tocopherol with aggressive prostate cancer among current smokers,” The Journal of Nutrition, vol. 141, no. 9, pp. 1731–1737, 2011. View at Publisher · View at Google Scholar · View at Scopus
  107. B. Mohelnikova-Duchonova, L. Marsakova, D. Vrana et al., “Superoxide dismutase and nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase polymorphisms and pancreatic cancer risk,” Pancreas, vol. 40, no. 1, pp. 72–78, 2011. View at Publisher · View at Google Scholar · View at Scopus
  108. J. Zhang, X. Zhang, I. B. Dhakal, M. D. Gross, F. F. Kadlubar, and K. E. Anderson, “Sequence variants in antioxidant defense and DNA repair genes, dietary antioxidants, and pancreatic cancer risk,” International Journal of Molecular Epidemiology and Genetics, vol. 2, no. 3, pp. 236–244, 2011. View at Google Scholar
  109. M. Atoum, M. Abdel-Fattah, N. Nimer, S. Abdel-Rahman, and S. A. Abdeldayem, “Association of alanine-valine manganese superoxide dismutase gene polymorphism and microheterogeneity manganese superoxide dismutase activity in breast cancer and benign breast tissue,” Journal of Breast Cancer, vol. 15, no. 2, pp. 157–161, 2012. View at Publisher · View at Google Scholar · View at Scopus
  110. H. Farawela, M. Khorshied, I. Shaheen et al., “The association between hepatitis C virus infection, genetic polymorphisms of oxidative stress genes and B-cell non-Hodgkin’s lymphoma risk in Egypt,” Infection, Genetics and Evolution, vol. 12, no. 6, pp. 1189–1194, 2012. View at Publisher · View at Google Scholar · View at Scopus
  111. M. V. Hemelrijck, S. Rohrmann, A. Steinbrecher, R. Kaaks, B. Teucher, and J. Linseisen, “Heterocyclic aromatic amine [HCA] intake and prostate cancer risk: effect modification by genetic variants,” Nutrition and Cancer, vol. 64, no. 5, pp. 704–713, 2012. View at Publisher · View at Google Scholar · View at Scopus
  112. C. Kucukgergin, O. Sanli, A. S. Amasyali, T. Tefik, and S. Seckin, “Genetic variants of MnSOD and GPX1 and susceptibility to bladder cancer in a Turkish population,” Medical Oncology, vol. 29, no. 3, pp. 1928–1934, 2012. View at Publisher · View at Google Scholar · View at Scopus
  113. C. Kucukgergin, O. Sanli, T. Tefik, M. Aydin, F. Ozcan, and S. Seckin, “Increased risk of advanced prostate cancer associated with MnSOD Ala-9-Val gene polymorphism,” Molecular Biology Reports, vol. 39, no. 1, pp. 193–198, 2012. View at Publisher · View at Google Scholar · View at Scopus
  114. S. M. Tsai, S. H. Wu, M. F. Hou, Y. L. Chen, H. Ma, and L. Y. Tsai, “Oxidative stress-related enzyme gene polymorphisms and susceptibility to breast cancer in non-smoking, non-alcohol-consuming Taiwanese women: a case-control study,” Annals of Clinical Biochemistry: International Journal of Laboratory Medicine, vol. 49, no. 2, pp. 152–158, 2012. View at Publisher · View at Google Scholar · View at Scopus
  115. E. Ye, Y. Zhang, H. Wang, Y. Shi, and L. Chen, “Association of MnSOD single nucleotide polymorphism with the occurrence and clinical outcome of nasopharyngeal carcinoma in Cantonese,” Journal of Southern Medical University, vol. 32, no. 6, pp. 798–801, 2012. View at Google Scholar
  116. P. Zhao, L. Zhao, P. Zou et al., “Genetic oxidative stress variants and glioma risk in a Chinese population: a hospital-based case–control study,” BMC Cancer, vol. 12, no. 1, p. 617, 2012. View at Publisher · View at Google Scholar · View at Scopus
  117. S. Amr, R. Dawson, D.’. A. Saleh et al., “Pesticides, gene polymorphisms, and bladder cancer among Egyptian agricultural workers,” Archives of Environmental & Occupational Health, vol. 70, no. 1, pp. 19–26, 2013. View at Publisher · View at Google Scholar · View at Scopus
  118. W. Ashour, M. Fathy, M. Hamed, O. Youssif, and N. Fawzy, “Association between environmental tobacco smoke exposure and lung cancer susceptibility: modification by antioxidant enzymes genetic polymorphisms,” Egyptian Journal of Chest Diseases and Tuberculosis, vol. 62, no. 4, pp. 781–788, 2013. View at Publisher · View at Google Scholar
  119. W. Attatippaholkun and K. Wikainapakul, “Predominant genotypes and alleles of two functional polymorphisms in the manganese superoxide dismutase gene are not associated with Thai cervical or breast cancer,” Asian Pacific Journal of Cancer Prevention, vol. 14, no. 6, pp. 3955–3961, 2013. View at Publisher · View at Google Scholar · View at Scopus
  120. A. Eken, O. Erdem, Z. Arsova-Sarafinovska et al., “Association between gene polymorphism of manganese superoxide dismutase and prostate cancer risk,” Journal of Biochemical and Molecular Toxicology, vol. 27, no. 3, pp. 213–218, 2013. View at Publisher · View at Google Scholar · View at Scopus
  121. L. Han, S. W. Lee, J. H. Yoon et al., “Association of SOD1 and SOD2 single nucleotide polymorphisms with susceptibility to gastric cancer in a Korean population,” APMIS, vol. 121, no. 3, pp. 246–256, 2013. View at Publisher · View at Google Scholar · View at Scopus
  122. C. Méplan, L. O. Dragsted, G. Ravn-Haren, A. Tjønneland, U. Vogel, and J. Hesketh, “Association between polymorphisms in glutathione peroxidase and selenoprotein P genes, glutathione peroxidase activity, HRT use and breast cancer risk,” PLoS One, vol. 8, no. 9, article e73316, 2013. View at Publisher · View at Google Scholar · View at Scopus
  123. D. Atilgan, B. S. Parlaktas, N. Uluocak et al., “The relationship between ALA16VAL single gene polymorphism and renal cell carcinoma,” Advances in Urology, vol. 2014, Article ID 932481, 5 pages, 2014. View at Publisher · View at Google Scholar · View at Scopus
  124. Y. Liu, L. Zha, B. Li, L. Zhang, T. Yu, and L. Li, “Correlation between superoxide dismutase 1 and 2 polymorphisms and susceptibility to oral squamous cell carcinoma,” Experimental and Therapeutic Medicine, vol. 7, no. 1, pp. 171–178, 2014. View at Publisher · View at Google Scholar · View at Scopus
  125. N. А. Oskina, N. А. Еrmolenko, U. А. Boyarskih et al., “Associations between SNPs within antioxidant genes and the risk of prostate cancer in the Siberian region of Russia,” Pathology & Oncology Research, vol. 20, no. 3, pp. 635–640, 2014. View at Publisher · View at Google Scholar · View at Scopus
  126. A. L. Brown, P. J. Lupo, M. F. Okcu, C. C. Lau, S. Rednam, and M. E. Scheurer, “SOD2 genetic variant associated with treatment-related ototoxicity in cisplatin-treated pediatric medulloblastoma,” Cancer Medicine, vol. 4, no. 11, pp. 1679–1686, 2015. View at Publisher · View at Google Scholar · View at Scopus
  127. E. Jablonska, J. Gromadzinska, B. Peplonska et al., “Lipid peroxidation and glutathione peroxidase activity relationship in breast cancer depends on functional polymorphism of GPX1,” BMC Cancer, vol. 15, no. 1, p. 657, 2015. View at Publisher · View at Google Scholar · View at Scopus
  128. B. S. Parlaktas, D. Atilgan, Y. Gencten et al., “A pilot study of the association of manganese superoxide dismutase and glutathione peroxidase 1 single gene polymorphisms with prostate cancer and serum prostate specific antigen levels,” Archives of Medical Science, vol. 11, no. 5, pp. 994–1000, 2015. View at Publisher · View at Google Scholar · View at Scopus
  129. S. Su, K. He, J. Li et al., “Genetic polymorphisms in antioxidant enzyme genes and susceptibility to hepatocellular carcinoma in Chinese population: a case-control study,” Tumour Biology, vol. 36, no. 6, pp. 4627–4632, 2015. View at Publisher · View at Google Scholar · View at Scopus
  130. S. W. Kang, “Superoxide dismutase 2 gene and cancer risk: evidence from an updated meta-analysis,” International Journal of Clinical and Experimental Medicine, vol. 8, no. 9, pp. 14647–14655, 2015. View at Google Scholar
  131. A. Bag and N. Bag, “Target sequence polymorphism of human manganese superoxide dismutase gene and its association with cancer risk: a review,” Cancer Epidemiology Biomarkers & Prevention, vol. 17, no. 12, pp. 3298–3305, 2008. View at Publisher · View at Google Scholar · View at Scopus
  132. Z. Meng and H. Shi, “Association between genetic polymorphisms of antioxidant enzyme genes and susceptibility to hepatocellular carcinoma: a meta-analysis,” International Journal of Clinical and Experimental Medicine, vol. 9, pp. 15645–15655, 2016. View at Google Scholar
  133. F. Jin, W. J. Xiong, J. C. Jing, Z. Feng, L. S. Qu, and X. Z. Shen, “Evaluation of the association studies of single nucleotide polymorphisms and hepatocellular carcinoma: a systematic review,” Journal of Cancer Research and Clinical Oncology, vol. 137, no. 7, pp. 1095–1104, 2011. View at Publisher · View at Google Scholar · View at Scopus
  134. G. G. Sun, Y. D. Wang, Y. F. Lu, and W. N. Hu, “Different association of manganese superoxide dismutase gene polymorphisms with risk of prostate, esophageal, and lung cancers: evidence from a meta-analysis of 20,025 subjects,” Asian Pacific Journal of Cancer Prevention, vol. 14, no. 3, pp. 1937–1943, 2013. View at Publisher · View at Google Scholar · View at Scopus
  135. C. Mao, L. X. Qiu, P. Zhan et al., “MnSOD Val16Ala polymorphism and prostate cancer susceptibility: a meta-analysis involving 8,962 Subjects,” Journal of Cancer Research and Clinical Oncology, vol. 136, no. 7, pp. 975–979, 2010. View at Publisher · View at Google Scholar · View at Scopus
  136. G. Liu, G. Sun, Y. Wang, D. Wang, W. Hu, and J. Zhang, “Association between manganese superoxide dismutase gene polymorphism and breast cancer risk: a meta-analysis of 17,842 subjects,” Molecular Medicine Reports, vol. 6, no. 4, pp. 797–804, 2012. View at Publisher · View at Google Scholar · View at Scopus
  137. L. X. Qiu, L. Yao, C. Mao et al., “Lack of association between MnSOD Val16Ala polymorphism and breast cancer risk: a meta-analysis involving 58,448 subjects,” Breast Cancer Research and Treatment, vol. 123, no. 2, pp. 543–547, 2010. View at Publisher · View at Google Scholar · View at Scopus
  138. S. Young-McCaughan, “Potential for prostate cancer prevention through physical activity,” World Journal of Urology, vol. 30, no. 2, pp. 167–179, 2012. View at Publisher · View at Google Scholar · View at Scopus
  139. G. Bresciani, I. B. M. Cruz, J. A. de Paz, M. J. Cuevas, and J. González-Gallego, “The MnSOD Ala16Val SNP: relevance to human diseases and interaction with environmental factors,” Free Radical Research, vol. 47, no. 10, pp. 781–792, 2013. View at Publisher · View at Google Scholar · View at Scopus