Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

Oxidative stress in susceptibility to breast cancer: study in Spanish population

Authors: Patricia Rodrigues, Griselda de Marco, Jessica Furriol, Maria Luisa Mansego, Mónica Pineda-Alonso, Anna Gonzalez-Neira, Juan Carlos Martin-Escudero, Javier Benitez, Ana Lluch, Felipe J Chaves, Pilar Eroles

Published in: BMC Cancer | Issue 1/2014

Login to get access

Abstract

Background

Alterations in the redox balance are involved in the origin, promotion and progression of cancer. Inter-individual differences in the oxidative stress regulation can explain a part of the variability in cancer susceptibility.
The aim of this study was to evaluate if polymorphisms in genes codifying for the different systems involved in oxidative stress levels can have a role in susceptibility to breast cancer.

Methods

We have analyzed 76 single base polymorphisms located in 27 genes involved in oxidative stress regulation by SNPlex technology. First, we have tested all the selected SNPs in 493 breast cancer patients and 683 controls and we have replicated the significant results in a second independent set of samples (430 patients and 803 controls). Gene-gene interactions were performed by the multifactor dimensionality reduction approach.

Results

Six polymorphisms rs1052133 (OGG1), rs406113 and rs974334 (GPX6), rs2284659 (SOD3), rs4135225 (TXN) and rs207454 (XDH) were significant in the global analysis. The gene-gene interactions demonstrated a significant four-variant interaction among rs406113 (GPX6), rs974334 (GPX6), rs105213 (OGG1) and rs2284659 (SOD3) (p-value = 0.0008) with high-risk genotype combination showing increased risk for breast cancer (OR = 1.75 [95% CI; 1.26-2.44]).

Conclusions

The results of this study indicate that different genotypes in genes of the oxidant/antioxidant pathway could affect the susceptibility to breast cancer. Furthermore, our study highlighted the importance of the analysis of the epistatic interactions to define with more accuracy the influence of genetic variants in susceptibility to breast cancer.
Appendix
Available only for authorised users
Literature
1.
Dumitrescu RG, Cotarla I: Understanding breast cancer risk – where do we stand in 2005?. J Cell Mol Med. 2005, 9 (1): 208-221. 10.1111/j.1582-4934.2005.tb00350.x.CrossRefPubMed
2.
Stratton MR, Rahman N: The emerging landscape of breast cancer susceptibility. Nat Genet. 2008, 40 (1): 17-22. 10.1038/ng.2007.53.CrossRefPubMed
3.
Sun Y: Free radicals, antioxidant enzymes, and carcinogenesis. Free Radic Biol Med. 1990, 8 (6): 583-599. 10.1016/0891-5849(90)90156-D.CrossRefPubMed
4.
Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J: Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007, 39 (1): 44-84. 10.1016/j.biocel.2006.07.001.CrossRefPubMed
5.
Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M: Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact. 2006, 160 (1): 1-40. 10.1016/j.cbi.2005.12.009.CrossRefPubMed
6.
Parri M, Chiarugi P: Redox molecular machines involved in tumor progression. Antioxid Redox Signal. 2013, 19 (15): 1828-1845. 10.1089/ars.2012.5040.CrossRefPubMed
7.
Scott TL, Rangaswamy S, Wicker CA, Izumi T: Repair of oxidative DNA damage and cancer: recent progress in DNA base excision repair. Antioxid Redox Signal. 2014, 20 (4): 708-726. 10.1089/ars.2013.5529.CrossRefPubMedPubMedCentral
8.
Cerutti PA: Prooxidant states and tumor promotion. Science. 1985, 227 (4685): 375-381. 10.1126/science.2981433.CrossRefPubMed
9.
Trush MA, Kensler TW: An overview of the relationship between oxidative stress and chemical carcinogenesis. Free Radic Biol Med. 1991, 10 (3–4): 201-209.CrossRefPubMed
10.
Costa A, Scholer-Dahirel A, Mechta-Grigoriou F: The role of reactive oxygen species and metabolism on cancer cells and their microenvironment. Semin Cancer Biol. 2014, 25: 23-32.CrossRefPubMed
11.
Trachootham D, Lu W, Ogasawara MA, Nilsa RD, Huang P: Redox regulation of cell survival. Antioxid Redox Signal. 2008, 10 (8): 1343-1374. 10.1089/ars.2007.1957.CrossRefPubMedPubMedCentral
12.
Elchuri S, Oberley TD, Qi W, Eisenstein RS, Jackson Roberts L, Van Remmen H, Epstein CJ, Huang TT: CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life. Oncogene. 2005, 24 (3): 367-380. 10.1038/sj.onc.1208207.CrossRefPubMed
13.
Neumann CA, Krause DS, Carman CV, Das S, Dubey DP, Abraham JL, Bronson RT, Fujiwara Y, Orkin SH, Van Etten RA: Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression. Nature. 2003, 424 (6948): 561-565. 10.1038/nature01819.CrossRefPubMed
14.
Acharya A, Das I, Chandhok D, Saha T: Redox regulation in cancer: a double-edged sword with therapeutic potential. Oxid Med Cell Longev. 2010, 3 (1): 23-34. 10.4161/oxim.3.1.10095.CrossRefPubMedPubMedCentral
15.
Fang J, Seki T, Maeda H: Therapeutic strategies by modulating oxygen stress in cancer and inflammation. Adv Drug Deliv Rev. 2009, 61 (4): 290-302. 10.1016/j.addr.2009.02.005.CrossRefPubMed
16.
Ivanova D, Bakalova R, Lazarova D, Gadjeva V, Zhelev Z: The impact of reactive oxygen species on anticancer therapeutic strategies. Adv Clin Exp Med. 2013, 22 (6): 899-908.PubMed
17.
Milaeva ER: Metal-based antioxidants–potential therapeutic candidates for prevention the oxidative stress-related carcinogenesis: mini-review. Curr Top Med Chem. 2011, 11 (21): 2703-2713. 10.2174/156802611798040741.CrossRefPubMed
18.
Cebrian A, Pharoah PD, Ahmed S, Smith PL, Luccarini C, Luben R, Redman K, Munday H, Easton DF, Dunning AM, Ponder BA: Tagging single-nucleotide polymorphisms in antioxidant defense enzymes and susceptibility to breast cancer. Cancer Res. 2006, 66 (2): 1225-1233. 10.1158/0008-5472.CAN-05-1857.CrossRefPubMed
19.
Seibold P, Hein R, Schmezer P, Hall P, Liu J, Dahmen N, Flesch-Janys D, Popanda O, Chang-Claude J: Polymorphisms in oxidative stress-related genes and postmenopausal breast cancer risk. Int J Cancer. 2011, 129 (6): 1467-1476. 10.1002/ijc.25761.CrossRefPubMed
20.
Hirschhorn JN, Daly MJ: Genome-wide association studies for common diseases and complex traits. Nat Rev Genet. 2005, 6 (2): 95-108.CrossRefPubMed
21.
Tobler AR, Short S, Andersen MR, Paner TM, Briggs JC, Lambert SM, Wu PP, Wang Y, Spoonde AY, Koehler RT, Peyret N, Chen C, Broomer AJ, Ridzon DA, Zhou H, Hoo BS, Hayashibara KC, Leong LN, Ma CN, Rosenblum BB, Day JP, Ziegle JS, De La Vega FM, Rhodes MD, Hennessy KM, Wenz HM: The SNPlex genotyping system: a flexible and scalable platform for SNP genotyping. J Biomol Tech. 2005, 16 (4): 398-406.PubMedPubMedCentral
22.
Sole X, Guino E, Valls J, Iniesta R, Moreno V: SNPStats: a web tool for the analysis of association studies. Bioinformatics. 2006, 22 (15): 1928-1929. 10.1093/bioinformatics/btl268.CrossRefPubMed
23.
Moore JH, Gilbert JC, Tsai CT, Chiang FT, Holden T, Barney N, White BC: A flexible computational framework for detecting, characterizing, and interpreting statistical patterns of epistasis in genetic studies of human disease susceptibility. J Theor Biol. 2006, 241 (2): 252-261. 10.1016/j.jtbi.2005.11.036.CrossRefPubMed
24.
Ritchie MD, Hahn LW, Moore JH: Power of multifactor dimensionality reduction for detecting gene-gene interactions in the presence of genotyping error, missing data, phenocopy, and genetic heterogeneity. Genet Epidemiol. 2003, 24 (2): 150-157. 10.1002/gepi.10218.CrossRefPubMed
25.
Ritchie MD, Hahn LW, Roodi N, Bailey LR, Dupont WD, Parl FF, Moore JH: Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer. Am J Hum Genet. 2001, 69 (1): 138-147. 10.1086/321276.CrossRefPubMedPubMedCentral
26.
Banerjee M, Vats P: Reactive metabolites and antioxidant gene polymorphisms in type 2 diabetes mellitus. Indian J Hum Genet. 2014, 20 (1): 10-19. 10.4103/0971-6866.132747.CrossRefPubMedPubMedCentral
27.
dos Santos KG, Canani LH, Gross JL, Tschiedel B, Souto KE, Roisenberg I: The catalase -262C/T promoter polymorphism and diabetic complications in Caucasians with type 2 diabetes. Dis Markers. 2006, 22 (5–6): 355-359.CrossRefPubMed
28.
Tarnai I, Csordas M, Sukei E, Shemirani AH, Kaplar M, Goth L: Effect of C111T polymorphism in exon 9 of the catalase gene on blood catalase activity in different types of diabetes mellitus. Free Radic Res. 2007, 41 (7): 806-811. 10.1080/10715760701381778.CrossRefPubMed
29.
Ambrosone CB, Freudenheim JL, Thompson PA, Bowman E, Vena JE, Marshall JR, Graham S, Laughlin R, Nemoto T, Shields PG: Manganese superoxide dismutase (MnSOD) genetic polymorphisms, dietary antioxidants, and risk of breast cancer. Cancer Res. 1999, 59 (3): 602-606.PubMed
30.
Cox DG, Tamimi RM, Hunter DJ: Gene x Gene interaction between MnSOD and GPX-1 and breast cancer risk: a nested case–control study. BMC Cancer. 2006, 6: 217-10.1186/1471-2407-6-217.CrossRefPubMedPubMedCentral
31.
Ravn-Haren G, Olsen A, Tjonneland A, Dragsted LO, Nexo BA, Wallin H, Overvad K, Raaschou-Nielsen O, Vogel U: Associations between GPX1 Pro198Leu polymorphism, erythrocyte GPX activity, alcohol consumption and breast cancer risk in a prospective cohort study. Carcinogenesis. 2006, 27 (4): 820-825.CrossRefPubMed
32.
Tsai SM, Wu SH, Hou MF, Chen YL, Ma H, Tsai LY: Oxidative stress-related enzyme gene polymorphisms and susceptibility to breast cancer in non-smoking, non-alcohol-consuming Taiwanese women: a case–control study. Ann Clin Biochem. 2012, 49 (Pt 2): 152-158.CrossRefPubMed
33.
Cha MK, Suh KH, Kim IH: Overexpression of peroxiredoxin I and thioredoxin1 in human breast carcinoma. J Exp Clin Cancer Res. 2009, 28: 93-10.1186/1756-9966-28-93.CrossRefPubMedPubMedCentral
34.
Penney RB, Roy D: Thioredoxin-mediated redox regulation of resistance to endocrine therapy in breast cancer. Biochim Biophys Acta. 2013, 1836 (1): 60-79.PubMed
35.
Bostrom B, Erdmann G: Cellular pharmacology of 6-mercaptopurine in acute lymphoblastic leukemia. Am J Pediatr Hematol Oncol. 1993, 15 (1): 80-86. 10.1097/00043426-199302000-00010.CrossRefPubMed
36.
Van Ness B, Ramos C, Haznadar M, Hoering A, Haessler J, Crowley J, Jacobus S, Oken M, Rajkumar V, Greipp P, Barlogie B, Durie B, Katz M, Atluri G, Fang G, Gupta R, Steinbach M, Kumar V, Mushlin R, Johnson D, Morgan G: Genomic variation in myeloma: design, content, and initial application of the Bank On A Cure SNP Panel to detect associations with progression-free survival. BMC Med. 2008, 6: 26-10.1186/1741-7015-6-26.CrossRefPubMedPubMedCentral
37.
Hubackova M, Vaclavikova R, Ehrlichova M, Mrhalova M, Kodet R, Kubackova K, Vrana D, Gut I, Soucek P: Association of superoxide dismutases and NAD(P)H quinone oxidoreductases with prognosis of patients with breast carcinomas. Int J Cancer. 2012, 130 (2): 338-348. 10.1002/ijc.26006.CrossRefPubMed
38.
Rajaraman P, Hutchinson A, Rothman N, Black PM, Fine HA, Loeffler JS, Selker RG, Shapiro WR, Linet MS, Inskip PD: Oxidative response gene polymorphisms and risk of adult brain tumors. Neuro Oncol. 2008, 10 (5): 709-715. 10.1215/15228517-2008-037.CrossRefPubMedPubMedCentral
39.
Gu D, Wang M, Zhang Z, Chen J: Lack of association between the hOGG1 Ser326Cys polymorphism and breast cancer risk: evidence from 11 case–control studies. Breast Cancer Res Treat. 2010, 122 (2): 527-531. 10.1007/s10549-009-0723-4.CrossRefPubMed
40.
Romanowicz-Makowska H, Smolarz B, Makowski M, Polac I, Pertynski T: Ser326Cys polymorphism in DNA repair genes hOGG1 in breast cancer women. Pol J Pathol. 2008, 59 (4): 201-204.PubMed
41.
Yuan W, Xu L, Feng Y, Yang Y, Chen W, Wang J, Pang D, Li D: The hOGG1 Ser326Cys polymorphism and breast cancer risk: a meta-analysis. Breast Cancer Res Treat. 2010, 122 (3): 835-842. 10.1007/s10549-009-0722-5.CrossRefPubMed
42.
Sangrajrang S, Schmezer P, Burkholder I, Waas P, Boffetta P, Brennan P, Bartsch H, Wiangnon S, Popanda O: Polymorphisms in three base excision repair genes and breast cancer risk in Thai women. Breast Cancer Res Treat. 2008, 111 (2): 279-288. 10.1007/s10549-007-9773-7.CrossRefPubMed
43.
Synowiec E, Stefanska J, Morawiec Z, Blasiak J, Wozniak K: Association between DNA damage, DNA repair genes variability and clinical characteristics in breast cancer patients. Mutat Res. 2008, 648 (1–2): 65-72.CrossRefPubMed
44.
Cai Q, Shu XO, Wen W, Courtney R, Dai Q, Gao YT, Zheng W: Functional Ser326Cys polymorphism in the hOGG1 gene is not associated with breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2006, 15 (2): 403-404. 10.1158/1055-9965.EPI-05-0868.CrossRefPubMed
45.
Choi JY, Hamajima N, Tajima K, Yoo KY, Yoon KS, Park SK, Kim SU, Lee KM, Noh DY, Ahn SH, Choe KJ, Han W, Hirvonen A, Kang D: hOGG1 Ser326Cys polymorphism and breast cancer risk among Asian women. Breast Cancer Res Treat. 2003, 79 (1): 59-62. 10.1023/A:1023305826726.CrossRefPubMed
46.
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 (11): e27545-10.1371/journal.pone.0027545.CrossRefPubMedPubMedCentral
47.
Hirano T: Repair system of 7, 8-dihydro-8-oxoguanine as a defense line against carcinogenesis. J Radiat Res. 2008, 49 (4): 329-340. 10.1269/jrr.08049.CrossRefPubMed
48.
49.
50.
Osorio A, Milne R, Kuchenbaecker K, Vaclová T, Pita G, Alonso R, Peterlongo P, Blanco I: DNA glycosylases involved in Base Excision Repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers. Plos Genet. 2014, 10 (4): e1004256-10.1371/journal.pgen.1004256.CrossRefPubMedPubMedCentral
51.
Andrew AS, Karagas MR, Nelson HH, Guarrera S, Polidoro S, Gamberini S, Sacerdote C, Moore JH, Kelsey KT, Demidenko E, Vineis P, Matullo G: DNA repair polymorphisms modify bladder cancer risk: a multi-factor analytic strategy. Hum Hered. 2008, 65 (2): 105-118. 10.1159/000108942.CrossRefPubMed
52.
Gui J, Andrew AS, Andrews P, Nelson HM, Kelsey KT, Karagas MR, Moore JH: A robust multifactor dimensionality reduction method for detecting gene-gene interactions with application to the genetic analysis of bladder cancer susceptibility. Ann Hum Genet. 2011, 75 (1): 20-28. 10.1111/j.1469-1809.2010.00624.x.CrossRefPubMed
53.
Ihsan R, Chauhan PS, Mishra AK, Yadav DS, Kaushal M, Sharma JD, Zomawia E, Verma Y, Kapur S, Saxena S: Multiple analytical approaches reveal distinct gene-environment interactions in smokers and non smokers in lung cancer. PLoS One. 2011, 6 (12): e29431-10.1371/journal.pone.0029431.CrossRefPubMedPubMedCentral
54.
Su MW, Tung KY, Liang PH, Tsai CH, Kuo NW, Lee YL: Gene-gene and gene-environmental interactions of childhood asthma: a multifactor dimension reduction approach. PLoS One. 2012, 7 (2): e30694-10.1371/journal.pone.0030694.CrossRefPubMedPubMedCentral
55.
Chen X, Wang J, Guo W, Liu X, Sun C, Cai Z, Fan Y, Wang Y: Two functional variations in 5’-UTR of hoGG1 gene associated with the risk of breast cancer in Chinese. Breast Cancer Res Treat. 2011, 127 (3): 795-803. 10.1007/s10549-010-1284-2.CrossRefPubMed
56.
He C, Tamimi RM, Hankinson SE, Hunter DJ, Han J: A prospective study of genetic polymorphism in MPO, antioxidant status, and breast cancer risk. Breast Cancer Res Treat. 2009, 113 (3): 585-594. 10.1007/s10549-008-9962-z.CrossRefPubMed
57.
Oestergaard MZ, Tyrer J, Cebrian A, Shah M, Dunning AM, Ponder BA, Easton DF, Pharoah PD: Interactions between genes involved in the antioxidant defence system and breast cancer risk. Br J Cancer. 2006, 95 (4): 525-531. 10.1038/sj.bjc.6603272.CrossRefPubMedPubMedCentral
58.
McCullough LE, Santella RM, Cleveland RJ, Bradshaw PT, Millikan RC, North KE, Olshan AF, Eng SM, Ambrosone CB, Ahn J, Steck SE, Teitelbaum SL, Neugut AI, Gammon MD: Polymorphisms in oxidative stress genes, physical activity, and breast cancer risk. Cancer Causes Control. 2012, 23 (12): 1949-1958. 10.1007/s10552-012-0072-1.CrossRefPubMedPubMedCentral
59.
Rossner P, 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 (4): 811-815. 10.1158/1055-9965.EPI-05-0659.CrossRefPubMed
60.
Li Y, Ambrosone CB, McCullough MJ, Ahn J, Stevens VL, Thun MJ, Hong CC: Oxidative stress-related genotypes, fruit and vegetable consumption and breast cancer risk. Carcinogenesis. 2009, 30 (5): 777-784. 10.1093/carcin/bgp053.CrossRefPubMed
61.
Crawford A, Fassett RG, Geraghty DP, Kunde DA, Ball MJ, Robertson IK, Coombes JS: Relationships between single nucleotide polymorphisms of antioxidant enzymes and disease. Gene. 2012, 501 (2): 89-103. 10.1016/j.gene.2012.04.011.CrossRefPubMed
62.
Weiss JM, Goode EL, Ladiges WC, Ulrich CM: Polymorphic variation in hOGG1 and risk of cancer: a review of the functional and epidemiologic literature. Mol Carcinog. 2005, 42 (3): 127-141. 10.1002/mc.20067.CrossRefPubMed
Metadata
Title
Oxidative stress in susceptibility to breast cancer: study in Spanish population
Authors
Patricia Rodrigues
Griselda de Marco
Jessica Furriol
Maria Luisa Mansego
Mónica Pineda-Alonso
Anna Gonzalez-Neira
Juan Carlos Martin-Escudero
Javier Benitez
Ana Lluch
Felipe J Chaves
Pilar Eroles
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-861

Other articles of this Issue 1/2014

BMC Cancer 1/2014 Go to the issue

Research article

Increased incidence of head and neck cancer in liver transplant recipients: a meta-analysis

Research article

Predicting response to vascular endothelial growth factor inhibitor and chemotherapy in metastatic colorectal cancer

Research article

Evaluation of the walk-through inflatable colon as a colorectal cancer education tool: results from a pre and post research design

Research article

Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses vasculogenic mimicry and proliferation of highly aggressive pancreatic cancer PaTu8988 cells

Research article

High miR-449b expression in prostate cancer is associated with biochemical recurrence after radical prostatectomy

Research article

Peptide deformylase inhibitor actinonin reduces celastrol’s HSP70 induction while synergizing proliferation inhibition in tumor cells
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits