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Cancer Chemotherapy and Pharmacology

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Open Access 01-02-2010 | Original Article

MRP2 and GSTP1 polymorphisms and chemotherapy response in advanced non-small cell lung cancer

Authors: Ning Sun, Xinchen Sun, Baoan Chen, Hongyan Cheng, Jifeng Feng, Lu Cheng, Zuhong Lu

Published in: Cancer Chemotherapy and Pharmacology | Issue 3/2010

Abstract

Purpose

The level of drug metabolism and drug transport is correlated with the sensitivity of cancer cells towards platinum-based chemotherapy. We hypothesize that genetic polymorphisms in metabolising enzymes gene GSTP1 (glutathione S-transferase P1), and MRP2 (multidrug resistance-associated protein 2) (ABCC2), which result in inter-individual differences in metabolism and drug disposition, may predict clinical response to platinum agents in advanced non-small cell lung cancer (NSCLC) patients.

Methods

Totally 113 patients with advanced NSCLC were routinely treated with platinum-based chemotherapy, and clinical response was evaluated after four cycles. MRP2 C-24T (−24C>T), MRP2 Val417Ile (1249G>A), MRP2 Ile1324Ile (3972C>T), and GSTP1 Ile105Val (342A>G) genotype were determined by gene-chip method (a 3-D (three dimensions) polyacrylamide gel-based DNA microarray method) using DNA samples isolated from peripheral blood collected before treatment. Pearson Chi-square test and Fisher’s exact test were performed to measure the differences of the chemotherapeutic efficacy among variant genotype. The odds ratios and 95% confidence intervals were computed by logistic regression.

Results

The C→T change of MRP2 C-24T and the A→G change of GSTP1 Ile105Val polymorphism significantly increased platinum-based chemotherapy response.

Conclusion

The polymorphic status of MRP2 C-24T and GSTP1 Ile105Val might be the predictive markers for the treatment response of advanced NSCLC patients. The DNA microarray-based method is accurate, high throughput and inexpensive, suitable for single-nucleotide polymorphism genotyping in a large number of individuals.

Guilbert JJ (2003) The world health report 2002: reducing risks, promoting healthy life. Educ Health (Abingdon) 16(2):230CrossRef

Spiro SG, Silvestri GA (2005) The treatment of advanced non-small cell lung cancer. Curr Opin Pulm Med 11:287–291CrossRefPubMed

Breathnach O, Freidlin B, Conley B et al (2001) Twenty-two years of phase III trials for patients with advanced non-small cell lung cancer: sobering results. J Clin Oncol 19:1734–1742PubMed

Stephens RJ, Fairlamb D, Gower N, et al. (2002) The Big Lung Trial (BLT): determining the value of cisplatin-based chemotherapy for all patients with non-small cell lung cancer (NSCLC)—Preliminary results in the supportive care setting. Proc Am Soc Clin Oncol 21 (Abstract 1161)

Rabik CA, Dolan ME (2007) Molecular mechanisms of resistance and toxicity associated with platinating agents. Cancer Treat Rev 33(1):9–23CrossRefPubMed

Viktorsson K, De Petris L, Lewensohn R (2005) The role of p53 in treatment responses of lung cancer. Biochem Biophys Res Commun 331:868–880CrossRefPubMed

Strange RC, Spiteri MA, Ramachandran S, Fryer AA (2001) Glutathione-S transferase family of enzymes. Mutat Res 482(1–2):21–26PubMed

Fuertes MA, Castilla J, Alonso C et al (2003) Cisplatin biochemical mechanism of action: from cytotoxicity to induction of cell death through interconnections between apoptotic and necrotic pathways. Curr Med Chem 10:257–266

Mannervik B, Board PG, Hayes JD, Listowsky I, Pearson WR (2005) Nomenclature for mammalian soluble glutathione transferases. Methods Enzymol 401:1–8CrossRefPubMed

10.

Terrier P, Townsend AJ, Coindre JM, Triche TJ, Cowan KH (1990) An immunohistochemical study of pi class glutathione S-transferase expression in normal human tissue. Am J Pathol 137:845–853PubMed

11.

Anttila S, Hirvonen A, Vainio H, Husgafvel-Pursiainen K, Hayes JD, Ketterer B (1993) Immunohistochemical localization of glutathione S-transferases in human lung cancer. Cancer Res 53:5643–5648PubMed

12.

D’Al`o F, Voso MT, Guidi F et al (2004) Polymorphisms of CYP1A1 and glutathione S-transferase and susceptibility to adult acute myeloid leukemia. Haematologica 89(6):664–670

13.

Rebbeck TR (1997) Molecular epidemiology of the human glutathione S transferase genotypes GSTM1 and GSTT1 in cancer susceptibility. Cancer Epidemiol Biomarkers Prev 6(9):733–743PubMed

14.

Haimeur A, Conseil G, Deeley RG, Cole SP (2004) The MRP-related and BCRP/ABCG2 multidrug resistance proteins: biology, substrate specificity and regulation. Curr Drug Metab 5:21–53CrossRefPubMed

15.

Rebbeor JF, Connolly GC, Ballatori N (2002) Inhibition of Mrp2- and Ycf1p-mediated transport by reducing agents: evidence for GSH transport on rat MRP2. Biochim Biophys Acta 1559:171–178CrossRefPubMed

16.

Leslie EM, Haimeur A, Waalkes MP (2004) Arsenic transport by the human multidrug resistance protein 1 (MRP1/ABCC1): evidence that a tri-glutathione conjugate is required. J Biol Chem 279(31):32700–32708CrossRefPubMed

17.

Takano M, Yumoto R, Murakami T (2006) Expression and function of efflux drug transporters in the intestine. Pharmacol Ther 109:137–161CrossRefPubMed

18.

Borst P, Evers R, Kool M, Wijnholds J (2000) A family of drug transporters: the multidrug resistance-associated proteins. J Natl Cancer Inst 92:1295–1302CrossRefPubMed

19.

Taniguchi K, Wada M, Kohno K et al (1996) A human canalicular multispecific organic anion transporter (cMOAT) gene is overexpressed in cisplatin resistant human cancer cell lines with decreased drug accumulation. Cancer Res 56:4124–4129PubMed

20.

Bakos E, Evers R, Sinkule JA, Varadi A, Borst P, Sarkadi B (2000) Interactions of the human multidrug resistance proteins MRP1 and MRP2 with organic anions. Mol Pharmacol 57:760–768PubMed

21.

Bernig T, Chanock SJ (2006) Challenges of SNP genotyping and genetic variation: its future role in diagnosis and treatment of cancer. Expert Rev Mol Diagn 6:319–331CrossRefPubMed

22.

Miller AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Cancer 47:207–214CrossRefPubMed

23.

Xiao PF, Cheng L, Wan Y et al (2006) An improved gel-based DNA microarray method for detecting single nucleotide mismatch. Electrophoresis 27:3904–3915CrossRefPubMed

24.

Evans WE, Relling MV (1999) Pharmacogenomics: translating functional genomics into rational therapeutics. Science 286:487–491CrossRefPubMed

25.

Schiller JH, Harrington D, Belani CP et al (2002) Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. New Engl J Med 346:92–98CrossRefPubMed

26.

Zatloukal P, Petruzelka L, Zemanova M et al (2003) Gemcitabine plus cisplatin vs. gemcitabine plus carboplatin in stage IIIb and IV non-small cell lung cancer: a phase III randomized trial. Lung Cancer 41:321–331CrossRefPubMed

27.

Scagliotti GV, De Marinis F, Rinaldi M et al (2002) Phase III randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer. J Clin Oncol 20(21):4285–4291CrossRefPubMed

28.

Oguri T, Fujiwara Y, Katoh O et al (2000) Glutathione S transferase-pi gene expression and platinum drug exposure in human lung cancer. Cancer Lett 156:93–99CrossRefPubMed

29.

Rudin CM, Yang ZJ, Schumaker LM et al (2003) Inhibition of glutathione synthesis reverses Bcl-2-mediated cisplatin resistance. Cancer Res 63(2):312–318PubMed

30.

Goto S, Iida T, Cho S, Oka M, Kohno S, Kondo T (1999) Overexpression of glutathione S-transferase pi enhances the adduct formation of cisplatin with glutathione in human cancer cells. Free Radic Res 31(6):549–558CrossRefPubMed

31.

Harpole DH Jr, Moore MB, Herndon JEII, Aloia T, D’Amico TA, Sporn T (2001) The prognostic value of molecular marker analysis in patients treated with trimodality therapy for esophageal cancer. Clin Cancer Res 7(3):562–569PubMed

32.

Beeghly A, Katsaros D, Chen H et al (2006) Glutathione S-transferase polymorphisms and ovarian cancer treatment and survival. Gynecol Oncol 100(2):330–337CrossRefPubMed

33.

Hinoshita E, Uchiumi T, Taguchi K et al (2000) Increased expression of an ATP-binding cassette superfamily transporter, multidrug resistance protein 2, in human colorectal carcinomas. Clin Cancer Res 6:2401–2407PubMed

34.

Board PG, Weber GC, Coggan M (1989) Isolation of a cDNA clone and localization of the human glutathione S-transferase 3 genes to chromosome bands 11q13 and 12q13-14. Ann Hum Genet 53:205–213CrossRefPubMed

35.

Watson MA, Stewart RK, Smith GB, Massey TE, Bell DA (1998) Human glutathione S-transferase P1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution. Carcinogenesis 19(2):275–280CrossRefPubMed

36.

Allan JM, ChP Wild, Rollinson S et al (2001) Polymorphism in glutathione S-transferase P1 is associated with susceptibility to chemotherapy induced leukaemia. Proc Natl Acad Sci USA 98:11592–11597CrossRefPubMed

37.

Garte S, Gaspari L, Alexandrie AK et al (2001) Metabolic gene polymorphism frequencies in control populations. Cancer Epidemiol Biomarkers Prev 10(12):1239–1248PubMed

38.

Stoehlmacher J, Park DJ, Zhang W et al (2002) Association between glutathione S-transferase P1, T1, and M1 genetic polymorphism and survival of patients with metastatic colorectal cancer. J Natl Cancer Inst 94:936–942PubMed

39.

Stoehlmacher J, Park DJ, Zhang W et al (2004) A multivariate analysis of genomic polymorphisms: prediction of clinical outcome to 5-FU/oxaliplatin combination chemotherapy in refractory colorectal cancer. Br J Cancer 91:344–354PubMed

40.

Suzuki H, Sugiyama Y (2002) Single nucleotide polymorphisms in multidrug resistance associated protein 2 (MRP2/ABCC2): its impact on drug disposition. Adv Drug Deliv Rev 54(10):1311–1331CrossRefPubMed

41.

Ito S, Ieiri I, Tanabe M, Suzuki A, Higuchi S, Otsubo K (2001) Polymorphism of the ABC transporter genes, MDR1, MRP1 and MRP2/cMOAT, in healthy Japanese subjects. Pharmacogenetics 11:175–184CrossRefPubMed

42.

Sai K, Saito Y, Itoda M et al (2008) Genetic variations and haplotypes of ABCC2 encoding MRP2 in a Japanese population. Drug Metab Pharmacokinet 23(2):139–147CrossRefPubMed

43.

Itoda M, Saito Y, Soyama A et al (2002) Polymorphisms in the ABCC2 (cMOAT/MRP2) gene found in 72 established cell lines derived from Japanese individuals: an association between single nucleotide polymorphisms in the 59-untranslated region and exon 28. Drug Metab Dispos 30:363–364CrossRefPubMed

44.

Meyer zu Schwabedissen HE, Jedlitschky G, Gratz M et al (2005) Variable expression of MRP2 (ABCC2) in human placenta: influence of gestational age and cellular differentiation. Drug Metab Dispos 33:896–904CrossRefPubMed

45.

Haenisch S, Zimmermann U, Dazert E et al (2007) Influence of polymorphisms of ABCB1 and ABCC2 on mRNA and protein expression in normal and cancerous kidney cortex. Pharmacogenomics J 7:56–65CrossRefPubMed

46.

Han JY, Lim HS, Yoo YK et al (2007) Associations of ABCB1, ABCC2, and ABCG2 polymorphisms with irinotecan-pharmacokinetics and clinical outcome in patients with advanced non-small cell lung cancer. Cancer 110:138–147CrossRefPubMed

47.

Liedert B, Materna V, Schadendorf D, Thomale J, Lage H (2003) Overexpression of cMOAT(MRP2/ABCC2) is associated with decreased formation of platinum-DNA adducts and decreased G2-arrest in melanoma cells resistant to cisplatin. J Invest Dermatol 121(1):172–176CrossRefPubMed

48.

Yang XS, Masayuki S, Hitoshi K et al (2004) Single nucleotide polymorphisms in MRP2 gene and their significance on chemosensitivity of advanced ovarian cancer. J Pract Obstet Gynecol 20(3):153–155

49.

Rehman FN, Audeh M, Abrams ES, Hammond PW, Kenney M, Boles TC (1999) Immobilization of acrylamide-modified oligonucleotides by co-polymerization. Nucleic Acids Res 27:649–655CrossRefPubMed

50.

Wang Y, Zhang DD, Zheng WL et al (2008) Multiple gene methylation of nonsmall cell lung cancers evaluated with 3-dimensional microarray. Cancer 112:61325–61336

51.

Wan Y, Wang Y, Luo JF et al (2007) Bisulfite modification of immobilized DNAs for methylation detection. Biosens Bioelectron 22:2415–2421CrossRefPubMed

Title: MRP2 and GSTP1 polymorphisms and chemotherapy response in advanced non-small cell lung cancer
Authors: Ning Sun
Xinchen Sun
Baoan Chen
Hongyan Cheng
Jifeng Feng
Lu Cheng
Zuhong Lu
Publication date: 01-02-2010
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 3/2010
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-009-1046-1

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Purpose

Methods

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