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Lung cancer risk associated with selenium status is modified in smoking individuals by Sep15 polymorphism

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Abstract

Background

Selenium (Se) is a trace element suggested to act chemopreventive in lung cancer. The mechanism by which Se suppresses tumour development may be associated with some of the functions of selenoproteins, including 15 kDa selenoprotein (Sep15). This protein exhibits antioxidant properties and thus may be involved in the process of carcinogenesis. Recently, it has been shown that the genetic polymorphism of Sep15, resulting in different response of the protein to Se, is associated with the risk of breast and head and neck cancers.

Aim of the study

The aim of the study was to investigate the possible association between lung cancer risk and Sep15 polymorphism in combination with Se status in the Polish population.

Methods

The study concerned 325 cases and 287 controls. All the participants were smokers. Plasma Se concentration was determined using graphite furnace atomic absorption spectrometry, and Sep15 polymorphism (1125 G/A transition within 3′-untranslated region) was detected with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.

Results

The adjusted odds ratios (ORs) for lung cancer cases, compared to individuals with Sep15 wild type variant (GG), were: 0.91 (95% CI: 0.64–1.32) for the heterozygous variant (GA) and 0.80 (95% CI: 0.39–1.65) for the homozygous variant (AA). Although plasma Se concentration was statistically lower in lung cancer cases (49.4 ± 17.4 ng/ml) compared to controls (53.3 ± 14.0 ng/ml, p < 0.002), the analysis of the joint effect of Sep15 polymorphism and Se status for lung cancer development revealed that lung cancer risk differed between the Se15 genotype groups. An increasing Se concentration was associated with a decreased risk in all individuals; however, at Se concentration above 80 ng/ml, the risk started to increase in individuals possessing the Sep15 1125 GG or GA genotype.

Conclusions

It appears that among smoking individuals, those with the Sep15 1125 AA genotype may benefit most from a higher Se intake, whereas in those with the GG or GA genotype, a higher Se status may increase the risk for lung cancer.

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References

  1. Abidoye O, Ferguson MK, Salgia R (2007) Lung carcinoma in African Americans. Nat Clin Pract Oncol 4:118–129

    Article  Google Scholar 

  2. Apostolou S, Klein JO, Mitsuuchi Y, Shetler JN, Poulikakos PI, Jhanwar SC, Kruger WD, Testa JR (2004) Growth inhibition and induction of apoptosis in mesothelioma cells by selenium and dependence on selenoprotein SEP15 genotype. Oncogene 23:5032–5040

    Article  CAS  Google Scholar 

  3. Bockmühl U, Schwendel A, Dietel M, Petersen I (1996) Distinct patterns of chromosomal alterations in high- and low-grade head and neck squamous cell carcinoma. Cancer Res 56:5325–5329

    Google Scholar 

  4. Bukalis K, Alber D, Bukalis G, Behne D, Kyriakopoulos A (2007) Effects of selenium diet on expression of selenoproteins in the lung of the rat. Ann N Y Acad Sci 1095:467–472

    Article  CAS  Google Scholar 

  5. Bukalis K, Wolf C, Behne D, Kyriakopoulos A (2007) Studies on the selenoproteome in the cultured cells of lung and trachea by gel electrophoretic techniques. J Chromatogr A 1155:180–186

    Article  CAS  Google Scholar 

  6. Clark LC, Combs GF Jr, Turnbull BW, Slate EH, Chalker DK, Chow J, Davis LS, Glover RA, Graham GF, Gross EG, Krongrad A, Lesher JL Jr, Park HK, Sanders BB Jr, Smith CL, Taylor JR (1996) Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. JAMA 276:1957–1963

    Article  CAS  Google Scholar 

  7. Ferguson AD, Labunskyy VM, Fomenko DE, Araç D, Chelliah Y, Amezcua CA, Rizo J, Gladyshev VN, Deisenhofer J (2006) NMR structures of the selenoproteins Sep15 and SelM reveal redox activity of a new thioredoxin-like family. J Biol Chem 281:3536–3543

    Article  CAS  Google Scholar 

  8. Garland M, Morris JS, Stampfer MJ, Colditz GA, Spate VL, Baskett CK, Rosner B, Speizer FE, Willett WC, Hunter DJ (1995) Prospective study of toenail selenium levels and cancer among women. J Natl Cancer Inst 87:497–505

    Article  CAS  Google Scholar 

  9. Girard L, Zochbauer-Muller S, Virmani AK, Gazdar AF, Minna JD (2000) Genome-wide allelotyping of lung cancer identifies new regions of allelic loss, differences between small cell lung cancer and non-small cell lung cancer, and loci clustering. Cancer Res 60:4894–4906

    CAS  Google Scholar 

  10. Gladyshev VN, Jeang KT, Wootton JC, Hatfield DL (1998) A new human selenium-containing protein. Purification, characterization, and cDNA sequence. J Biol Chem 273:8910–8915

    Article  CAS  Google Scholar 

  11. Gromadzinska J, Wasowicz W, Rydzynski K, Szeszenia-Dabrowska N (2003) Oxidative-stress markers in blood of lung cancer patients occupationally exposed to carcinogens. Biol Trace Elem Res 91:203–215

    Article  CAS  Google Scholar 

  12. Haiman CA, Stram DO, Wilkens LR, Pike MC, Kolonel LN, Henderson BE, Le Marchand L (2006) Ethnic and racial differences in the smoking-related risk of lung cancer. N Engl J Med 354:333–342

    Article  CAS  Google Scholar 

  13. Hatfield DL, Gladyshev VN (2002) How selenium has altered our understanding of the genetic code. Mol Cell Biol 22:3565–3576

    Article  CAS  Google Scholar 

  14. Hu YJ, Korotkov KV, Mehta R, Hatfield DL, Rotimi CN, Luke A, Prewitt TE, Cooper RS, Stock W, Vokes EE, Dolan ME, Gladyshev VN, Diamond AM (2001) Distribution and functional consequences of nucleotide polymorphisms in the 3′-untranslated region of the human Sep15 gene. Cancer Res 61:2307–2310

    CAS  Google Scholar 

  15. Kalcklosch M, Kyriakopoulos A, Hammel C, Behne D (1995) A new selenoprotein found in the glandular epithelial cells of the rat prostate. Biochem Biophys Res Commun 217:162–170

    Article  CAS  Google Scholar 

  16. Knekt P, Marniemi J, Teppo L, Heliovaara M, Aromaa A (1998) Is low selenium status a risk factor for lung cancer? Am J Epidemiol 148:975–982

    CAS  Google Scholar 

  17. Kohno T, Yokota J (1999) How many tumor suppressor genes are involved in human lung carcinogenesis? Carcinogenesis 20:1403–1410

    Article  CAS  Google Scholar 

  18. Korotkov KV, Kumaraswamy E, Zhou Y, Hatfield DL, Gladyshev VN (2001) Association between the 15-kDa selenoprotein and UDP-glucose:glycoprotein glucosyltransferase in the endoplasmic reticulum of mammalian cells. J Biol Chem 276:15330–15336

    Article  CAS  Google Scholar 

  19. Kryukov GV, Castellano S, Novoselov SV, Lobanov AV, Zehtab O, Guigo R, Gladyshev VN (2003) Characterization of mammalian selenoproteomes. Science 300:1439–1443

    Article  CAS  Google Scholar 

  20. Kumaraswamy E, Malykh A, Korotkov KV, Kozyavkin S, Hu Y, Kwon SY, Moustafa ME, Carlson BA, Berry MJ, Lee BJ, Hatfield DL, Diamond AM, Gladyshev VN (2000) Structure–expression relationships of the 15-kDa selenoprotein gene. Possible role of the protein in cancer etiology. J Biol Chem 275:35540–35547

    Article  CAS  Google Scholar 

  21. Kyriakopoulos A, Bukalis K, Roethlein D, Hoppe B, Graebert A, Behne D (2004) Prevention against oxidative stress of eukaryotic cell membranes by selenium compounds of the rat. Ann N Y Acad Sci 1030:458–461

    Article  CAS  Google Scholar 

  22. Labunskyy VM, Ferguson AD, Fomenko DE, Chelliah Y, Hatfield DL, Gladyshev VN (2005) A novel cysteine-rich domain of Sep15 mediates the interaction with UDP-glucose:glycoprotein glucosyltransferase. J Biol Chem 280:37839–37845

    Article  CAS  Google Scholar 

  23. Letavayová L, Vlcková V, Brozmanová J (2006) Selenium: from cancer prevention to DNA damage. Toxicology 227:1–14

    Article  Google Scholar 

  24. Michelland S, Gazzeri S, Brambilla E, Robert-Nicoud M (1999) Comparison of chromosomal imbalances in neuroendocrine and non-small-cell lung carcinomas. Cancer Genet Cytogenet 114:22–30

    Article  CAS  Google Scholar 

  25. Nasr MA, Hu YJ, Diamond AM (2004) Allelic loss at the Sep15 locus in breast cancer. Cancer Ther 1:293–298

    Google Scholar 

  26. Neve J, Chamart S, Molle L (1987) Optimization of a direct procedure for the determination of selenium in plasma and erythrocytes using Zeeman effect atomic absorption spectroscopy. In: Brätter P, Schramel P (eds) Trace Elem-Anal Chem Med Biol., vol 2. Walter de Gruyter, Berlin, pp 349–358

    Google Scholar 

  27. Novoselov SV, Calvisi DF, Labunskyy VM, Factor VM, Carlson BA, Fomenko DE, Moustafa ME, Hatfield DL, Gladyshev VN (2005) Selenoprotein deficiency and high levels of selenium compounds can effectively inhibit hepatocarcinogenesis in transgenic mice. Oncogene 24:8003–8011

    Article  CAS  Google Scholar 

  28. Patterson EL, Milstrey R, Stokstad ELR (1957) Effect of selenium in preventing exudative diathesis in chicks. Proc Soc Exp Biol Med 95:617

    CAS  Google Scholar 

  29. Petersen I, Bujard M, Petersen S, Wolf G, Goeze A, Schwendel A, Langreck H, Gellert K, Reichel M, Just K, du Manoir S, Cremer T, Dietel M, Ried T (1997) Patterns of chromosomal imbalances in adenocarcinoma and squamous cell carcinoma of the lung. Cancer Res 57:2331–2335

    CAS  Google Scholar 

  30. Ragnarsson G, Eiriksdottir G, Johannsdottir JT, Jonasson JG, Egilsson V, Ingvarsson S (1999) Loss of heterozygosity at chromosome 1p in different solid human tumours: association with survival. Br J Cancer 79:1468–1474

    Article  CAS  Google Scholar 

  31. Rayman MP (2005) Selenium in cancer prevention: a review of the evidence and mechanism of action. Proc Nutr Soc 64:527–542

    Article  CAS  Google Scholar 

  32. Reid ME, Duffield-Lillico AJ, Garland L, Turnbull BW, Clark LC, Marshall JR (2002) Selenium supplementation and lung cancer incidence: an update of the nutritional prevention of cancer trial. Cancer Epidemiol Biomarkers Prev 11:1285–1291

    CAS  Google Scholar 

  33. Reszka E, Wasowicz W, Gromadzinska J, Winnicka R, Szymczak W (2005) Evaluation of selenium, zinc and copper levels related to GST genetic polymorphism in lung cancer patients. Biol Trace Elem Res 22:33–36

    Google Scholar 

  34. Schwarz K, Foltz CM (1957) Selenium as an integral part of factor 3 against dietary liver degeneration. J Am Chem Soc 79:3292

    Article  CAS  Google Scholar 

  35. van den Brandt PA, Goldbohm RA, van ‘t Veer P, Bode P, Dorant E, Hermus RJ, Sturmans F (1993) A prospective cohort study on selenium status and the risk of lung cancer. Cancer Res 53:4860–4865

    Google Scholar 

  36. Vogt TM, Ziegler RG, Patterson BH, Graubard BI (2007) Racial differences in serum selenium concentration: analysis of US population data from the Third National Health and Nutrition Examination Survey. Am J Epidemiol 166:280–288

    Article  Google Scholar 

  37. Whanger PD (2004) Selenium and its relationship to cancer: an update. Br J Nutr 91:11–28

    Article  CAS  Google Scholar 

  38. Wu HJ, Lin C, Zha YY, Yang JG, Zhang MC, Zhang XY, Liang X, Fu M, Wu M (2003) Redox reactions of Sep15 and its relationship with tumor development. Ai Zheng 22:119–122

    CAS  Google Scholar 

  39. Yu SY, Zhu YJ, Li WG (1997) Protective role of selenium against hepatitis B virus and primary liver cancer in Qidong. Biol Trace Elem Res 56:117–124

    Article  CAS  Google Scholar 

  40. Zhuo H, Smith AH, Steinmaus C (2004) Selenium and lung cancer: a quantitative analysis of heterogeneity in the current epidemiological literature. Cancer Epidemiol Biomarkers Prev 13:771–778

    CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by an internal grant (IMP 1.3/2006) and by the ECNIS Network of Excellence (Contract No. 513943/UE).

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Authors and Affiliations

  1. Dept. of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, 8 Teresy St., 91-348, Lodz, Poland

    Ewa Jablonska, Jolanta Gromadzinska, Edyta Reszka & Wojciech Wasowicz

  2. Dept. of Epidemiology, Nofer Institute of Occupational Medicine, Lodz, Poland

    Wojciech Sobala

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  1. Ewa Jablonska
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  2. Jolanta Gromadzinska
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  3. Wojciech Sobala
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  4. Edyta Reszka
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Correspondence to Ewa Jablonska.

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Jablonska, E., Gromadzinska, J., Sobala, W. et al. Lung cancer risk associated with selenium status is modified in smoking individuals by Sep15 polymorphism. Eur J Nutr 47, 47–54 (2008). https://doi.org/10.1007/s00394-008-0696-9

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  • DOI: https://doi.org/10.1007/s00394-008-0696-9

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