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Journal of Cancer Research and Clinical Oncology

Published in:

01-10-2011 | Original Paper

GPx-1 polymorphism (rs1050450) contributes to tumor susceptibility: evidence from meta-analysis

Authors: Jiawei Chen, Qiang Cao, Chao Qin, Pengfei Shao, Yilong Wu, Meilin Wang, Zhengdong Zhang, Changjun Yin

Published in: Journal of Cancer Research and Clinical Oncology | Issue 10/2011

Abstract

Purpose

Accumulating evidences implicate the selenium-containing cytosolic glutathione peroxidase, GPx-1, as a determinant of cancer risk and a mediator of the chemopreventive properties of selenium. Since the identification of a well-characterized functional polymorphism named Pro198Leu (rs1050450 C>T) in GPx-1, abundant studies have evaluated the association between Pro198Leu polymorphism and tumor risk in diverse population. But, the available results are conflicting.

Methods

To derive a more precise estimation, we performed a meta-analysis based on 14,372 cases with different tumor types and 18,081 controls from 31 published case–control studies. Published literature from PubMed was retrieved. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of the association.

Results

Overall, the results indicated that individuals who carried variant Leu allele (Pro/Leu and Leu/Leu) were associated with an increased cancer risk [odds ratio (OR) = 1.12, 95% confidence interval (CI) = 1.02–1.23] in a dominant genetic model. In further subgroup analyses, the increased risk of cancer was observed in subgroup of Asians and sample size more than 500 subjects.

Conclusion

These results suggest that the GPx-1 Pro198Leo polymorphism contributes to cancer susceptibility through a disturbed antioxidant balance.

Abiaka C, Al-Awadi F, Al-Sayer H, Gulshan S, Behbehani A, Farghally M (2002) Activities of erythrocyte antioxidant enzymes in cancer patients. J Clin Lab Anal 16(4):167–171. doi:10.1002/jcla.10037 PubMedCrossRef

Ahn J, Gammon MD, Santella RM, Gaudet MM, Britton JA, Teitelbaum SL, Terry MB, Neugut AI, Ambrosone CB (2005) No association between glutathione peroxidase Pro198Leu polymorphism and breast cancer risk. Cancer Epidemiol Biomarkers Prev 14(10):2459–2461. doi:10.1158/1055-9965.EPI-05-0459 PubMedCrossRef

Arsova-Sarafinovska Z, Matevska N, Eken A, Petrovski D, Banev S, Dzikova S, Georgiev V, Sikole A, Erdem O, Sayal A, Aydin A, Dimovski AJ (2009) Glutathione peroxidase 1 (GPX1) genetic polymorphism, erythrocyte GPX activity, and prostate cancer risk. Int Urol Nephrol 41(1):63–70. doi:10.1007/s11255-008-9407-y PubMedCrossRef

Beevi SS, Rasheed MH, Geetha A (2007) Evidence of oxidative and nitrosative stress in patients with cervical squamous cell carcinoma. Clin Chim Acta 375(1–2):119–123. doi:10.1016/j.cca.2006.06.028 PubMedCrossRef

Bhatti P, Stewart PA, Hutchinson A, Rothman N, Linet MS, Inskip PD, Rajaraman P (2009) Lead exposure, polymorphisms in genes related to oxidative stress, and risk of adult brain tumors. Cancer Epidemiol Biomarkers Prev 18(6):1841–1848. doi:10.1158/1055-9965.EPI-09-0197 PubMedCrossRef

Brigelius-Flohe R (1999) Tissue-specific functions of individual glutathione peroxidases. Free Radic Biol Med 27(9–10):951–965PubMedCrossRef

Brigelius-Flohe R, Kipp A (2009) Glutathione peroxidases in different stages of carcinogenesis. Biochim Biophys Acta 1790(11):1555–1568. doi:10.1016/j.bbagen.2009.03.006 PubMed

Cebrian A, Pharoah PD, Ahmed S, Smith PL, Luccarini C, Luben R, Redman K, Munday H, Easton DF, Dunning AM, Ponder BA (2006) Tagging single-nucleotide polymorphisms in antioxidant defense enzymes and susceptibility to breast cancer. Cancer Res 66(2):1225–1233. doi:10.1158/0008-5472.CAN-05-1857 PubMedCrossRef

Choi JY, Neuhouser ML, Barnett M, Hudson M, Kristal AR, Thornquist M, King IB, Goodman GE, Ambrosone CB (2007) Polymorphisms in oxidative stress-related genes are not associated with prostate cancer risk in heavy smokers. Cancer Epidemiol Biomarkers Prev 16(6):1115–1120. doi:10.1158/1055-9965.EPI-07-0040 PubMedCrossRef

Cooke MS, Evans MD, Dizdaroglu M, Lunec J (2003) Oxidative DNA damage: mechanisms, mutation, and disease. FASEB J 17(10):1195–1214. doi:10.1096/fj.02-0752rev PubMedCrossRef

Cox DG, Hankinson SE, Kraft P, Hunter DJ (2004) No association between GPX1 Pro198Leu and breast cancer risk. Cancer Epidemiol Biomarkers Prev 13 (11 Pt 1):1821–1822

de Haan JB, Bladier C, Griffiths P, Kelner M, O’Shea RD, Cheung NS, Bronson RT, Silvestro MJ, Wild S, Zheng SS, Beart PM, Hertzog PJ, Kola I (1998) Mice with a homozygous null mutation for the most abundant glutathione peroxidase, Gpx1, show increased susceptibility to the oxidative stress-inducing agents paraquat and hydrogen peroxide. J Biol Chem 273(35):22528–22536PubMedCrossRef

Durak I, Beduk Y, Kavutcu M, Ozturk S, Canbolat O, Ulutepe S (1997) Activities of superoxide dismutase and glutathione peroxidase enzymes in cancerous and non-cancerous human kidney tissues. Int Urol Nephrol 29(1):5–11PubMedCrossRef

Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634PubMed

Emerit I (1994) Reactive oxygen species, chromosome mutation, and cancer: possible role of clastogenic factors in carcinogenesis. Free Radic Biol Med 16(1):99–109PubMedCrossRef

Esworthy RS, Baker MA, Chu FF (1995) Expression of selenium-dependent glutathione peroxidase in human breast tumor cell lines. Cancer Res 55(4):957–962PubMed

Ezzikouri S, El Feydi AE, Afifi R, Benazzouz M, Hassar M, Pineau P, Benjelloun S (2010) Polymorphisms in antioxidant defence genes and susceptibility to hepatocellular carcinoma in a Moroccan population. Free Radic Res 44(2):208–216. doi:10.3109/10715760903402906 PubMedCrossRef

Feig DI, Reid TM, Loeb LA (1994) Reactive oxygen species in tumorigenesis. Cancer Res 54(7 Suppl):1890s–1894sPubMed

Forsberg L, de Faire U, Morgenstern R (2001) Oxidative stress, human genetic variation, and disease. Arch Biochem Biophys 389(1):84–93. doi:10.1006/abbi.2001.2295 PubMedCrossRef

Foster CB, Aswath K, Chanock SJ, McKay HF, Peters U (2006) Polymorphism analysis of six selenoprotein genes: support for a selective sweep at the glutathione peroxidase 1 locus (3p21) in Asian populations. BMC Genet 7:56. doi:10.1186/1471-2156-7-56 PubMedCrossRef

Goerlitz DS, El Daly M, Abdel-Hamid M, Saleh D, Golman L, El-Kafrawy S, Hifnawy T, Ezzat S, Abdel-Aziz MA, Zaghloul MS, Ali Saber R, Khaled H, Amr S, Zheng YL, Mikhail NN, Loffredo C (2011) GSTM1, GSTT1 null variants and GPX1 single nucleotide polymorphism are not associated with bladder cancer risk in Egypt. Cancer Epidemiol Biomarkers Prev. doi:10.1158/1055-9965.EPI-10-1306

Hansen R, Saebo M, Skjelbred CF, Nexo BA, Hagen PC, Bock G, Bowitz Lothe IM, Johnson E, Aase S, Hansteen IL, Vogel U, Kure EH (2005) GPX Pro198Leu and OGG1 Ser326Cys polymorphisms and risk of development of colorectal adenomas and colorectal cancer. Cancer Lett 229(1):85–91. doi:10.1016/j.canlet.2005.04.019 PubMedCrossRef

Hansen RD, Krath BN, Frederiksen K, Tjonneland A, Overvad K, Roswall N, Loft S, Dragsted LO, Vogel U, Raaschou-Nielsen O (2009) GPX1 Pro(198)Leu polymorphism, erythrocyte GPX activity, interaction with alcohol consumption and smoking, and risk of colorectal cancer. Mutat Res 664(1–2):13–19. doi:10.1016/j.mrfmmm.2009.01.009 PubMed

He C, Qureshi AA, Han J (2011) Polymorphisms in genes involved in oxidative stress and their interactions with lifestyle factors on skin cancer risk. J Dermatol Sci 60(1):54–56. doi:10.1016/j.jdermsci.2010.07.003 CrossRef

Hesketh J (2008) Nutrigenomics and selenium: gene expression patterns, physiological targets, and genetics. Annu Rev Nutr 28:157–177. doi:10.1146/annurev.nutr.28.061807.155446 PubMedCrossRef

Hu YJ, Diamond AM (2003) Role of glutathione peroxidase 1 in breast cancer: loss of heterozygosity and allelic differences in the response to selenium. Cancer Res 63(12):3347–3351PubMed

Hu YJ, Dolan ME, Bae R, Yee H, Roy M, Glickman R, Kiremidjian-Schumacher L, Diamond AM (2004) Allelic loss at the GPx-1 locus in cancer of the head and neck. Biol Trace Elem Res 101(2):97–106. doi:10.1385/BTER:101:2:097 PubMedCrossRef

Ichimura Y, Habuchi T, Tsuchiya N, Wang L, Oyama C, Sato K, Nishiyama H, Ogawa O, Kato T (2004) Increased risk of bladder cancer associated with a glutathione peroxidase 1 codon 198 variant. J Urol 172(2):728–732. doi:10.1097/01.ju.0000130942.40597.9d PubMedCrossRef

Ishida K, Morino T, Takagi K, Sukenaga Y (1987) Nucleotide sequence of a human gene for glutathione peroxidase. Nucleic Acids Res 15(23):10051PubMedCrossRef

Klaunig JE, Kamendulis LM, Hocevar BA (2010) Oxidative stress and oxidative damage in carcinogenesis. Toxicol Pathol 38(1):96–109. doi:10.1177/0192623309356453 PubMedCrossRef

Knight JA, Onay UV, Wells S, Li H, Shi EJ, Andrulis IL, Ozcelik H (2004) Genetic variants of GPX1 and SOD2 and breast cancer risk at the Ontario site of the Breast Cancer Family Registry. Cancer Epidemiol Biomarkers Prev 13(1):146–149PubMedCrossRef

Lau J, Ioannidis JP, Schmid CH (1997) Quantitative synthesis in systematic reviews. Ann Intern Med 127(9):820–826PubMed

Lee CH, Lee KY, Choe KH, Hong YC, Noh SI, Eom SY, Ko YJ, Zhang YW, Yim DH, Kang JW, Kim H, Kim YD (2006) Effects of oxidative DNA damage and genetic polymorphism of the glutathione peroxidase 1 (GPX1) and 8-oxoguanine glycosylase 1 (hOGG1) on lung cancer. J Prev Med Public Health 39(2):130–134PubMed

Lightfoot TJ, Skibola CF, Smith AG, Forrest MS, Adamson PJ, Morgan GJ, Bracci PM, Roman E, Smith MT, Holly EA (2006) Polymorphisms in the oxidative stress genes, superoxide dismutase, glutathione peroxidase and catalase and risk of non-Hodgkin’s lymphoma. Haematologica 91(9):1222–1227PubMed

Liu F, Liu L, Li B, Wei YG, Yan LN, Wen TF, Xu MQ, Wang WT, Yang JY (2011) p73 G4C14-A4T14 polymorphism and cancer risk: a meta-analysis based on 27 case–control studies. Mutagenesis. doi:10.1093/mutage/ger018

Loft S, Poulsen HE (1996) Cancer risk and oxidative DNA damage in man. J Mol Med 74(6):297–312PubMedCrossRef

Meplan C, Hughes DJ, Pardini B, Naccarati A, Soucek P, Vodickova L, Hlavata I, Vrana D, Vodicka P, Hesketh JE (2010) Genetic variants in selenoprotein genes increase risk of colorectal cancer. Carcinogenesis 31(6):1074–1079. doi:10.1093/carcin/bgq076 PubMedCrossRef

Midgette AS, Wong JB, Beshansky JR, Porath A, Fleming C, Pauker SG (1994) Cost-effectiveness of streptokinase for acute myocardial infarction: a combined meta-analysis and decision analysis of the effects of infarct location and of likelihood of infarction. Med Decis Making 14(2):108–117PubMedCrossRef

Oberley TD, Oberley LW (1997) Antioxidant enzyme levels in cancer. Histol Histopathol 12(2):525–535PubMed

Paz-y-Mino C, Munoz MJ, Lopez-Cortes A, Cabrera A, Palacios A, Castro B, Paz-y-Mino N, Sanchez ME (2010) Frequency of polymorphisms pro198leu in GPX-1 gene and ile58thr in MnSOD gene in the altitude Ecuadorian population with bladder cancer. Oncol Res 18(8):395–400PubMedCrossRef

Pharoah PD, Dunning AM, Ponder BA, Easton DF (2004) Association studies for finding cancer-susceptibility genetic variants. Nat Rev Cancer 4(11):850–860. doi:10.1038/nrc1476 PubMedCrossRef

Raaschou-Nielsen O, Sorensen M, Hansen RD, Frederiksen K, Tjonneland A, Overvad K, Vogel U (2007) GPX1 Pro198Leu polymorphism, interactions with smoking and alcohol consumption, and risk for lung cancer. Cancer Lett 247(2):293–300. doi:10.1016/j.canlet.2006.05.006 PubMedCrossRef

Rajaraman P, Hutchinson A, Rothman N, Black PM, Fine HA, Loeffler JS, Selker RG, Shapiro WR, Linet MS, Inskip PD (2008) Oxidative response gene polymorphisms and risk of adult brain tumors. Neuro Oncol 10(5):709–715. doi:10.1215/15228517-2008-037 PubMedCrossRef

Ratnasinghe D, Tangrea JA, Andersen MR, Barrett MJ, Virtamo J, Taylor PR, Albanes D (2000) Glutathione peroxidase codon 198 polymorphism variant increases lung cancer risk. Cancer Res 60(22):6381–6383PubMed

Ravn-Haren G, Olsen A, Tjonneland A, Dragsted LO, Nexo BA, Wallin H, Overvad K, Raaschou-Nielsen O, Vogel U (2006) Associations between GPX1 Pro198Leu polymorphism, erythrocyte GPX activity, alcohol consumption and breast cancer risk in a prospective cohort study. Carcinogenesis 27(4):820–825. doi:10.1093/carcin/bgi267 PubMedCrossRef

Reszka E, Gromadzinska J, Jablonska E, Wasowicz W, Jablonowski Z, Sosnowski M (2009) Level of selenoprotein transcripts in peripheral leukocytes of patients with bladder cancer and healthy individuals. Clin Chem Lab Med 47(9):1125–1132. doi:10.1515/CCLM.2009.261 PubMedCrossRef

Rosenberger A, Illig T, Korb K, Klopp N, Zietemann V, Wolke G, Meese E, Sybrecht G, Kronenberg F, Cebulla M, Degen M, Drings P, Groschel A, Konietzko N, Kreymborg KG, Haussinger K, Hoffken G, Jilge B, Ko YD, Morr H, Schmidt C, Schmidt EW, Tauscher D, Bickeboller H, Wichmann HE (2008) Do genetic factors protect for early onset lung cancer? A case control study before the age of 50 years. BMC Cancer 8:60. doi:10.1186/1471-2407-8-60 PubMedCrossRef

Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science 179(73):588–590PubMedCrossRef

Skrzydlewska E, Sulkowski S, Koda M, Zalewski B, Kanczuga-Koda L, Sulkowska M (2005) Lipid peroxidation and antioxidant status in colorectal cancer. World J Gastroenterol 11(3):403–406PubMed

Skuladottir H, Autrup H, Autrup J, Tjoenneland A, Overvad K, Ryberg D, Haugen A, Olsen JH (2005) Polymorphisms in genes involved in xenobiotic metabolism and lung cancer risk under the age of 60 years. A pooled study of lung cancer patients in Denmark and Norway. Lung Cancer 48(2):187–199. doi:10.1016/j.lungcan.2004.10.013

Steinbrecher A, Meplan C, Hesketh J, Schomburg L, Endermann T, Jansen E, Akesson B, Rohrmann S, Linseisen J (2010) Effects of selenium status and polymorphisms in selenoprotein genes on prostate cancer risk in a prospective study of European men. Cancer Epidemiol Biomarkers Prev 19(11):2958–2968. doi:10.1158/1055-9965.EPI-10-0364 PubMedCrossRef

Tang H, Dong X, Day RS, Hassan MM, Li D (2010) Antioxidant genes, diabetes and dietary antioxidants in association with risk of pancreatic cancer. Carcinogenesis 31(4):607–613. doi:10.1093/carcin/bgp310 PubMedCrossRef

Tas F, Hansel H, Belce A, Ilvan S, Argon A, Camlica H, Topuz E (2005) Oxidative stress in breast cancer. Med Oncol 22(1):11–15. doi:10.1385/MO:22:1:011 PubMedCrossRef

Vogel U, Olsen A, Wallin H, Overvad K, Tjonneland A, Nexo BA (2004) No association between GPX Pro198Leu and risk of basal cell carcinoma. Cancer Epidemiol Biomarkers Prev 13(8):1412–1413PubMed

Wang J, Sun T, Yang M, Lin DX, Tan W, Li KJ, Xiao Y (2008) Association of genetic polymorphisms in selenoprotein GPX1 and TXNRD2 with genetic susceptibility of gastric cancer. Zhonghua Yu Fang Yi Xue Za Zhi 42(7):511–514PubMed

Wu SH, Lee KW, Chen CH, Lin CC, Tseng YM, Ma H, Tsai SM, Tsai LY (2010) Epistasis of oxidative stress-related enzyme genes on modulating the risks in oral cavity cancer. Clin Chim Acta 411(21–22):1705–1710. doi:10.1016/j.cca.2010.07.007 PubMedCrossRef

Yang P, Bamlet WR, Ebbert JO, Taylor WR, de Andrade M (2004) Glutathione pathway genes and lung cancer risk in young and old populations. Carcinogenesis 25(10):1935–1944. doi:10.1093/carcin/bgh203 PubMedCrossRef

Zachara BA, Szewczyk-Golec K, Tyloch J, Wolski Z, Szylberg T, Stepien S, Kwiatkowski S, Bloch-Boguslawska E, Wasowicz W (2005) Blood and tissue selenium concentrations and glutathione peroxidase activities in patients with prostate cancer and benign prostate hyperplasia. Neoplasma 52(3):248–254PubMed

Zhuo P, Diamond AM (2009) Molecular mechanisms by which selenoproteins affect cancer risk and progression. Biochim Biophys Acta 1790(11):1546–1554. doi:10.1016/j.bbagen.2009.03.004 PubMed

Title: GPx-1 polymorphism (rs1050450) contributes to tumor susceptibility: evidence from meta-analysis
Authors: Jiawei Chen
Qiang Cao
Chao Qin
Pengfei Shao
Yilong Wu
Meilin Wang
Zhengdong Zhang
Changjun Yin
Publication date: 01-10-2011
Publisher: Springer-Verlag
Published in: Journal of Cancer Research and Clinical Oncology / Issue 10/2011
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-011-1033-x

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