Tumor Biology

, Volume 37, Issue 2, pp 2275–2284 | Cite as

Effect of transporter and DNA repair gene polymorphisms to lung cancer chemotherapy toxicity

  • Juan Chen
  • Lin Wu
  • Ying Wang
  • Jiye Yin
  • Xiangping Li
  • Zhan Wang
  • Huihua Li
  • Ting Zou
  • Chenyue Qian
  • Chuntian Li
  • Wei Zhang
  • Honghao Zhou
  • Zhaoqian Liu
Original Article

Abstract

Lung cancer is the first leading cause of cancer deaths. Chemotherapy toxicity is one of factors that limited the efficacy of platinum-based chemotherapy in lung cancer patients. Transporters and DNA repair genes play critical roles in occurrence of platinum-based chemotherapy toxicity. To investigate the relationships between transporter and DNA repair gene polymorphisms and platinum-based chemotherapy toxicity in lung cancer patients, we selected 60 polymorphisms in 14 transporters and DNA repair genes. The polymorphisms were genotyped in 317 lung cancer patients by Sequenom MassARRAY. Logistic regression was performed to estimate the association of toxicity outcome with the polymorphisms by PLINK. Our results showed that polymorphisms of SLC2A1 (rs3738514, rs4658, rs841844) were significantly related to overall toxicity. XRCC5 (rs1051685, rs6941) and AQP2 (10875989, rs3759125) polymorphisms were associated with hematologic toxicity. AQP2 polymorphisms (rs461872, rs7305534) were correlated with gastrointestinal toxicity. In conclusion, genotypes of these genes may be used to predict the platinum-based chemotherapy toxicity in lung cancer patients.

Keywords

Lung cancer Platinum Chemotherapy toxicity Genetic polymorphism Transporter DNA repair gene 

Notes

Acknowledgments

This work was supported by the National High-tech R&D Program of China (863 Program) (2012AA02A517, 2012AA02A518), National Natural Science Foundation of China (81173129, 81202595, 81373490, 81273595), and the Fundamental Research Funds for the Central Universities of Central South University (2015zzts116).

Conflicts of interest

None

References

  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA: Cancer J Clin. 2015;65:5–29.Google Scholar
  2. 2.
    Lebwohl D, Canetta R. Clinical development of platinum complexes in cancer therapy: an historical perspective and an update. Eur J Cancer. 1998;34:1522–34.CrossRefPubMedGoogle Scholar
  3. 3.
    Spreckelmeyer S, Orvig C, Casini A. Cellular transport mechanisms of cytotoxic metallodrugs: an overview beyond cisplatin. Molecules. 2014;19:15584–610.CrossRefPubMedGoogle Scholar
  4. 4.
    Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol. 2014;740:364–78.CrossRefPubMedGoogle Scholar
  5. 5.
    Cavaletti G, Ceresa C, Nicolini G, Marmiroli P. Neuronal drug transporters in platinum drugs-induced peripheral neurotoxicity. Anticancer Res. 2014;34:483–6.PubMedGoogle Scholar
  6. 6.
    Sprowl JA, Ness RA, Sparreboom A. Polymorphic transporters and platinum pharmacodynamics. Drug Metab Pharmacokinet. 2013;28:19–27.CrossRefPubMedGoogle Scholar
  7. 7.
    Martin LP, Hamilton TC, Schilder RJ. Platinum resistance: the role of DNA repair pathways. Clin Cancer Res: Off J Am Assoc Cancer Res. 2008;14:1291–5.CrossRefGoogle Scholar
  8. 8.
    Efferth T, Volm M. Pharmacogenetics for individualized cancer chemotherapy. Pharmacol Ther. 2005;107:155–76.CrossRefPubMedGoogle Scholar
  9. 9.
    Wang Y, Yin JY, Li XP, Chen J, Qian CY, Zheng Y, et al. The association of transporter genes polymorphisms and lung cancer chemotherapy response. PLoS One. 2014;9, e91967.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Wang Y, Li XP, Yin JY, Zhang Y, He H, Qian CY, et al. Association of hmgb1 and hmgb2 genetic polymorphisms with lung cancer chemotherapy response. Clin Exp Pharmacol Physiol. 2014;41:408–15.CrossRefPubMedGoogle Scholar
  11. 11.
    Li XP, Yin JY, Wang Y, He H, Li X, Gong WJ, et al. The atp7b genetic polymorphisms predict clinical outcome to platinum-based chemotherapy in lung cancer patients. Tumour Biol: J Int Soc Oncodevelopmental Biol Med. 2014;35:8259–65.CrossRefGoogle Scholar
  12. 12.
    Wang Z, Xu B, Lin D, Tan W, Leaw S, Hong X, et al. Xrcc1 polymorphisms and severe toxicity in lung cancer patients treated with cisplatin-based chemotherapy in Chinese population. Lung Cancer. 2008;62:99–104.CrossRefPubMedGoogle Scholar
  13. 13.
    Giachino DF, Ghio P, Regazzoni S, Mandrile G, Novello S, Selvaggi G, et al. Prospective assessment of xpd lys751gln and xrcc1 arg399gln single nucleotide polymorphisms in lung cancer. Clin Cancer Res: Off J Am Assoc Cancer Res. 2007;13:2876–81.CrossRefGoogle Scholar
  14. 14.
    Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. Plink: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81:559–75.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Suls A, Mullen SA, Weber YG, Verhaert K, Ceulemans B, Guerrini R, et al. Early-onset absence epilepsy caused by mutations in the glucose transporter glut1. Ann Neurol. 2009;66:415–9.CrossRefPubMedGoogle Scholar
  16. 16.
    De Grandis E, Stagnaro M, Biancheri R, Giannotta M, Gobbi G, Traverso M, et al. Lack of slc2a1 (glucose transporter 1) mutations in 30 Italian patients with alternating hemiplegia of childhood. J Child Neurol. 2013;28:863–6.CrossRefPubMedGoogle Scholar
  17. 17.
    Mullen SA, Marini C, Suls A, Mei D, Della Giustina E, Buti D, et al. Glucose transporter 1 deficiency as a treatable cause of myoclonic astatic epilepsy. Arch Neurol. 2011;68:1152–5.CrossRefPubMedGoogle Scholar
  18. 18.
    Agostinelli S, Traverso M, Accorsi P, Beccaria F, Belcastro V, Capovilla G, et al. Early-onset absence epilepsy: Slc2a1 gene analysis and treatment evolution. Eur J Neurol: Off J Eur Fed Neurol Soc. 2013;20:856–9.CrossRefGoogle Scholar
  19. 19.
    Du B, Liu S, Cui C, Wang S, Cui W. Association between glucose transporter 1 rs841853 polymorphism and type 2 diabetes mellitus risk may be population specific (1rs8418532). J Diab. 2013;5:291–9.CrossRefGoogle Scholar
  20. 20.
    Cormier CM, Au KS, Northrup H. A 10 bp deletion polymorphism and 2 new variations in the glut1 gene associated with meningomyelocele. Reprod Sci. 2011;18:463–8.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Amann T, Kirovski G, Bosserhoff AK, Hellerbrand C. Analysis of a promoter polymorphism of the glut1 gene in patients with hepatocellular carcinoma. Mol Membr Biol. 2011;28:182–6.CrossRefPubMedGoogle Scholar
  22. 22.
    Song K, Li M, Xu XJ, Xuan L, Huang GN, Song XL, et al. Hif-1alpha and glut1 gene expression is associated with chemoresistance of acute myeloid leukemia. Asian Pac J Cancer Prev: APJCP. 2014;15:1823–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Liu W, Fang Y, Wang XT, Liu J, Dan X, Sun LL. Overcoming 5-fu resistance of colon cells through inhibition of glut1 by the specific inhibitor wzb117. Asian Pac J Cancer Prev: APJCP. 2014;15:7037–41.CrossRefPubMedGoogle Scholar
  24. 24.
    Featherstone C, Jackson SP. Ku, a DNA repair protein with multiple cellular functions? Mutat Res. 1999;434:3–15.CrossRefPubMedGoogle Scholar
  25. 25.
    Long XD, Zhao D, Wang C, Huang XY, Yao JG, Ma Y, et al. Genetic polymorphisms in DNA repair genes xrcc4 and xrcc5 and aflatoxin b1-related hepatocellular carcinoma. Epidemiology. 2013;24:671–81.CrossRefPubMedGoogle Scholar
  26. 26.
    Zhao P, Zou P, Zhao L, Yan W, Kang C, Jiang T, et al. Genetic polymorphisms of DNA double-strand break repair pathway genes and glioma susceptibility. BMC Cancer. 2013;13:234.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Zhou LP, Luan H, Dong XH, Jin GJ, Man DL, Shang H. Association between xrcc5, 6 and 7 gene polymorphisms and the risk of breast cancer: a huge review and meta-analysis. Asian Pac J Cancer Prev: APJCP. 2012;13:3637–43.CrossRefPubMedGoogle Scholar
  28. 28.
    Knepper MA, Wade JB, Terris J, Ecelbarger CA, Marples D, Mandon B, et al. Renal aquaporins. Kidney Int. 1996;49:1712–7.CrossRefPubMedGoogle Scholar
  29. 29.
    Hall MD, Okabe M, Shen DW, Liang XJ, Gottesman MM. The role of cellular accumulation in determining sensitivity to platinum-based chemotherapy. Annu Rev Pharmacol Toxicol. 2008;48:495–535.CrossRefPubMedGoogle Scholar
  30. 30.
    Kishore BK, Krane CM, Di Iulio D, Menon AG, Cacini W. Expression of renal aquaporins 1, 2, and 3 in a rat model of cisplatin-induced polyuria. Kidney Int. 2000;58:701–11.CrossRefPubMedGoogle Scholar
  31. 31.
    Holmes RP. The role of renal water channels in health and disease. Mol Asp Med. 2012;33:547–52.CrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Juan Chen
    • 1
    • 2
    • 3
  • Lin Wu
    • 4
  • Ying Wang
    • 4
  • Jiye Yin
    • 1
    • 2
    • 3
  • Xiangping Li
    • 1
    • 2
  • Zhan Wang
    • 5
  • Huihua Li
    • 6
  • Ting Zou
    • 1
    • 2
  • Chenyue Qian
    • 1
    • 2
  • Chuntian Li
    • 7
  • Wei Zhang
    • 1
    • 2
    • 3
  • Honghao Zhou
    • 1
    • 2
    • 3
  • Zhaoqian Liu
    • 1
    • 2
    • 3
  1. 1.Department of Clinical Pharmacology, Xiangya HospitalCentral South UniversityChangshaPeople’s Republic of China
  2. 2.Institute of Clinical PharmacologyCentral South University, Hunan Key Laboratory of PharmacogeneticsChangshaPeople’s Republic of China
  3. 3.Hunan Province Cooperation Innovation Center for Molecular Target New Drug StudyHengyangPeople’s Republic of China
  4. 4.The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaPeople’s Republic of China
  5. 5.Department of Oncology, Xiangya HospitalCentral South UniversityChangshaPeople’s Republic of China
  6. 6.Division of Pulmonary, Allergy, and Critical Care Medicine, Department of MedicineUniversity of PittsburghPittsburghUSA
  7. 7.Department of RadiotherapyShenyangPeople’s Republic of China

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