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Microsomal glutathione S-transferase gene polymorphisms and colorectal cancer risk in a Han Chinese population

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Abstract

Background and aims

Glutathione S-transferases (GSTs) are phase II detoxification enzymes. Human GSTs have been classified into cytosolic, mitochondrial, and microsomal families. Several studies reported the association of colorectal cancer (CRC) risk with the genetic polymorphisms of cytosolic GSTs. The microsomal GSTs are structurally distinct but functionally similar to cytosolic GSTs; their association with CRC has not been reported. In this report, we summarized the result of a case-control study aimed at investigating the association of MGST1 gene locus polymorphisms with CRC risk among Han Chinese.

Patient/methods

Three hundred and seventy-two healthy controls and 238 sporadic CRC patients participated in this study. DNA resequencing was conducted for the 3.4 kb genomic DNA region containing the promoter, exons, exon–intron junctions, and the 5′ and 3′ untranslated regions.

Results

We detected 13 single nucleotide polymorphisms (SNPs) including four novel SNPs not reported in database/literature. The gene shows a much higher nucleotide diversity than most human genes. The linkage and recombination analysis revealed 24 common haplotypes (13% ≥ freq ≥ 1%) and identified extensive intragenic recombination throughout the MGST1 locus (R = 81.8). Significant CRC association (P < = 0.005) was not detected for each individual SNP. However, SNPs 102G>A and 16416G>A reached a marginal level of statistical significance with P values of 0.016 and 0.078, respectively. A combined genotype analysis detected a statistically significant CRC association for individuals carrying 102G>A/16416G>A (GG/GG) genotype (adjusted OR, 1.682; 95% confidence interval (CI), 1.177–2.404; P = 0.004). Consistent with the results of genotype analysis, the GG haplotype (102G>A/16416G>A) with two risk alleles was associated with a significantly higher CRC risk comparing with the haplotypes with one or no risk allele (adjusted OR 1.744; 95% CI 1.309–2.322; P = 0.0001).

Conclusion

The results suggest that MGST1 polymorphisms may contribute to CRC risk among Han Chinese.

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References

  1. Stewart BW, Kleihues P (2003) Colorectal cancer. World cancer report. IARC, Lyon, pp 163–166

    Google Scholar 

  2. Parkin DM, Whelan SL, Ferlay J, Raymond L, Young J (1997) Cancer incidence in five continents vol VII. IARC Scientific Publications, Lyon

    Google Scholar 

  3. Marchand LL (1999) Combined influence of genetic and dietary factors on colorectal cancer incidence in Japanese Americans. J Natl Cancer Inst Monogr 26:101–105

    PubMed  Google Scholar 

  4. Lafuente MJ, Casterad X, Trias M, Ascaso C, Molina R, Ballesta A, Zheng S, Wiencke JK, Lafuente A (2000) NAD(P)H: quinone oxidoreductase-dependent risk for colorectal cancer and its association with the presence K-ras mutations in tumors. Carcinogenesis 21:1813–1819

    Article  PubMed  CAS  Google Scholar 

  5. Sugimura T (2000) Nutrition and dietary carcinogens. Carcinogenesis 21:387–395

    Article  PubMed  CAS  Google Scholar 

  6. Sachse C, Smith G, Wilkie MJV, Barrett JH, Waxman R, Sullivan F, Forman D, Bishop DT, Wolf CR, and the Colorectal Cancer Study Group (2002) A pharmacogenetic study to investigate the role of dietary carcinogens in the etiology of colorectal cancer. Carcinogenesis 23:1839–1849

    Article  PubMed  CAS  Google Scholar 

  7. Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767

    Article  PubMed  CAS  Google Scholar 

  8. Roberts-Thomson IC, Ryan P, Khoo KK, Hart WJ, McMichael AJ, Butler RN (1996) Diet, acetylator phenotype and risk of colorectal neoplasia. Lancet 347:1372–1374

    Article  PubMed  CAS  Google Scholar 

  9. de Jong MM, Nolte IM, te Meerman GJ, van der Graaf WT, de Vries EGE, Sijmons RH, Hofstra RM, Kleibeuker JH (2002) Low-penetrance genes and their involvement in colorectal cancer susceptibility. Cancer Epidemiol Biomarkers Prev 11:1332–1352

    PubMed  Google Scholar 

  10. Grady WM, Markowitz SD (2002) Genetic and epigenetic alterations in colon cancer. Annu Rev Genomics Hum Genet 3:101–128

    Article  PubMed  CAS  Google Scholar 

  11. Roediger WE, Babidge W (1997) Human colonocyte detoxification. Gut 41:731–734

    Article  PubMed  CAS  Google Scholar 

  12. Kiss I, Sandor J, Pajkos G, Bogner B, Hegedus G, Ember I, (2000) Colorectal cancer risk in relation to genetic polymorphism of cytochrome P450 1a1, 2E1, and glutathione-S-transferase M1 enzymes. Anticancer Res 20:519–522

    PubMed  CAS  Google Scholar 

  13. Zhong S, Wyllie AH, Barnes D, Wolf CR, Spurr NK (1993) Relationship between the GSTM1 genetic polymorphism and susceptibility to bladder, breast, and colon cancer. Carcinogenesis 14:1821–1824

    Article  PubMed  CAS  Google Scholar 

  14. Gawronska-Szklarz B, Lubinski J, Kladny J, Kurzawski G, Bielicki D, Wojcicki M, Sych Z, Musial HD (1999) Polymorphism of GSTM1 gene in patients with colorectal cancer and colonic polyps. Exp Toxicol Pathol 51:321–325

    PubMed  CAS  Google Scholar 

  15. Andersson C, Mosialou E, Weinander R, Morgenstern R (1994) Enzymology of microsomal glutathione S-transferase. Adv Pharmacol 27:19–35

    Article  PubMed  CAS  Google Scholar 

  16. Kelner MJ, Bagnell RD, Montoya MA, Estes LA, Forsberg L, Morgenstern R (2000) Structural organization of the microsomal glutathione S-transferase gene (MGST1) on chromosome 12p13.1–13.2. J Biol Chem 275:13000–13006

    Article  PubMed  CAS  Google Scholar 

  17. Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21(2):263–265

    Article  PubMed  CAS  Google Scholar 

  18. Stephens M, Donnelly P (2003) A comparison of Bayesian methods for haplotype reconstruction. Am J Hum Genet 73:1162–1169

    Article  PubMed  CAS  Google Scholar 

  19. Rozas J, Sanchez-DelBarrio JC, Messeguer X, Rozas R (2003) DnaSP, DNA polymorphism analyses by the coalescent and other methods. Bioinformatics 19:2496–2497

    Article  PubMed  CAS  Google Scholar 

  20. de Jong JL, Mohandas T, Tu CP (1990) The gene for the microsomal glutathione S-transferase is on human chromosome 12. Genomics 6:379–382

    Article  Google Scholar 

  21. Iida A, Saito S, Sekine A, Kitamura Y, Mishima C, Osawa S, Kondo K, Harigae S, Nakamura Y (2001) Catalog of 434 single-nucleotide polymorphisms (SNPs) in genes of the alcohol dehydrogenase, glutathione S-transferase genes, and nicotineamide adenine dinucleotide, reduced (NADH) ubiquinone oxidoreductase families. J Hum Genet 46:385–407

    Article  PubMed  CAS  Google Scholar 

  22. Nei M (1987) Molecular evolutionary genetics. Columbia Univ. Press, New York

    Google Scholar 

  23. Li WH (1997) Molecular evolution. Sinauer Associates, Sunderland, MA

    Google Scholar 

  24. Watterson GA (1975) On the number of segregating sites in genetical models without recombination. Theor Popul Biol 7:256–276

    Article  PubMed  CAS  Google Scholar 

  25. Tajima F (1989) Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123:585–595

    PubMed  CAS  Google Scholar 

  26. Bader JS (2001) The relative power of SNPs and haplotype as genetic markers for association tests. Pharmacogenomics 2:11–24

    Article  PubMed  CAS  Google Scholar 

  27. Lohmueller KE, Wong LJ, Mauney MM, Jiang L, Felder RA, Jose PA, Williams SM (2005) Patterns of genetic variation in the hypertension candidate gene GRK4: ethnic variation and haplotype structure. Ann Hum Genet 70:27–41

    Article  CAS  Google Scholar 

  28. Stephens JC, Schneider JA, Tanguay DA, Choi J, Acharya T, Stanley SE, Jiang R, Messer CJ, Chew A, Han JH, Duan J, Carr JL, Lee MS, Koshy B, Kumar AM, Zhang G, Newell WR, Windemuth A, Xu C, Kalbfleisch TS, Shaner SL, Arnold K, Schulz V, Drysdale CM, Nandabalan K, Judson RS, Ruano G, Vovis GF (2001) Haplotype variation and linkage disequilibrium in 313 human genes. Science 293(5529):489–493

    Article  PubMed  CAS  Google Scholar 

  29. Li WH, Sadler LA (1991) Low nucleotide diversity in man. Genetics 129:513–523

    PubMed  CAS  Google Scholar 

  30. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES (1999) Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet 22:231–238

    Article  PubMed  CAS  Google Scholar 

  31. Halushka MK, Fan JB, Bentley K, Hsie L, Shen N, Weder A, Cooper R, Lipshutz R, Chakravarti A (1999) Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis. Nat Genet 22(3):239–247

    Article  PubMed  CAS  Google Scholar 

  32. Houlston RS, Tomlinson IP (2001) Polymorphisms and colorectal tumor risk. Gastroenterology 121:282–301

    Article  PubMed  CAS  Google Scholar 

  33. Abdel-Rahman SZ, Soliman AS, Bondy ML, Wu X, El-Badawy SA, Mahgoub KG, Ismail S, Seifeldin IA, Levin B (1999) Polymorphism of glutathione S-transferase loci GSTM1 and GSTT1 and susceptibility to colorectal cancer in Egypt. Cancer Lett 142:97–104

    Article  PubMed  CAS  Google Scholar 

  34. Hubbard AL, Harrison DJ, Moyes C, Wyllie AH, Cunningham C, Mannion E, Smith CA (1997) N-acetyltransferase 2 genotype in colorectal cancer and selective gene retention in cancers with chromosome 8p deletions. Gut 41:229–234

    Article  PubMed  CAS  Google Scholar 

  35. Cavalieri EL, Stack DE, Devanesan PD, Todorovic R, Dwivedy I, Higginbotham S, Johansson, SL, Patil KD, Gross ML, Gooden JK, Ramanathan R, Cerny RL, Rogan EG (1997) Molecular origin of cancer: catechol estrogen-3,4 quinones as endogenous tumor initiators. Proc Natl Acad Sci USA 94:10937–10942

    Article  PubMed  CAS  Google Scholar 

  36. Stack DE, Byun J, Gross ML, Rogan EG, Cavalieri EL (1996) Molecular characteristics of catechol estrogen quinines in reaction with deoxyribonucleosides. Chem Res Toxicol 9:851–859

    Article  PubMed  CAS  Google Scholar 

  37. Mendel DB, Hansen LP, Graves MK, Conley PB, Crabtree GR (1991) HNF-1 alpha and HNF-1 beta (vHNF-1) share dimerization and homeo domains, but not activation domains, and form heterodimers in vitro. Genes Dev 5:1042–1056

    Article  PubMed  CAS  Google Scholar 

  38. Rushmore TH, King RG, Paulson KE, Pickett CB (1990) Regulation of glutathione S-transferase Ya subunit gene expression: identification of a unique xenobiotic-responsive element controlling inducible expression by planar aromatic compounds. Proc Natl Acad Sci USA 87:3826–3830

    Article  PubMed  CAS  Google Scholar 

  39. Iida A, Saito S, Sekine A, Harigae S, Osawa S, Mishima C, Kondo K, Kitamura Y, Nakamura Y (2001) Catalog of 46 single-nucleotide polymorphisms (SNPs) in the microsomal glutathione S-transferase 1 (MGST1) gene. J Hum Genet 46:590–594

    Article  PubMed  CAS  Google Scholar 

  40. Luo Z, Hines RN (1996) Identification of multiple rabbit flavin-containing monooxygenase form 1 (FMO1) gene promoters and observation of tissue-specific DNase I hypersensitive sites. Arch Biochem Biophys 336:251–260

    Article  PubMed  CAS  Google Scholar 

  41. Hirokawa T, Seah BC, Mitaku S (1998) SOSUI: classification and secondary structure prediction system for membrane proteins. Bioinformatics 14:378–379

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We acknowledge the financial support of Grant HKUST6117/01M from RGC, Grant CMI03/04.SC03 from HKUST and Grant UPHMSGF 06/07.SC01 from Mochtar Riady Institute for nanotechnology.

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Authors and Affiliations

  1. Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, People’s Republic of China

    Hao Zhang, Ling-Hong Liao, Shuk-Ming Liu, Maria Li Lung & Madeline Wu

  2. Department of Surgery, Tuen Mun Hospital, Hong Kong SAR, People’s Republic of China

    Kwok-Wai Lau & Albert Kai-Cheong Lai

  3. Department of Respiratory, the Second Hospital affiliated to Dalian Medical University, Dalian, People’s Republic of China

    Jin-Hui Zhang & Qi Wang

  4. Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China

    Xiao-Qian Chen

  5. Mammary Gland Surgical Department, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China

    Wei Wei

  6. Ankang Hospital, Jinin, People’s Republic of China

    Hua Liu

  7. Institute of Genetics, Fudan University, Shanghai, People’s Republic of China

    Jian-Hua Cai

  8. Center for Cancer Research, Hong Kong University of Science and Technology, Hong Kong, People’s Republic of China

    Maria Li Lung & Madeline Wu

  9. Mochtar Riady Institute for Nanotechnology, Jl. Boulevard Jend. Sudirman, Lippo Karawaci Tangerang, Indonesia, 15811

    Susan S. W. Tai

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  1. Hao Zhang
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Correspondence to Hao Zhang.

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Zhang, H., Liao, LH., Liu, SM. et al. Microsomal glutathione S-transferase gene polymorphisms and colorectal cancer risk in a Han Chinese population. Int J Colorectal Dis 22, 1185–1194 (2007). https://doi.org/10.1007/s00384-007-0308-9

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