Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Article
  • Published:
Tumor Biology

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA: Cancer J Clin. 2015;65:5–29.

    Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  3. Spreckelmeyer S, Orvig C, Casini A. Cellular transport mechanisms of cytotoxic metallodrugs: an overview beyond cisplatin. Molecules. 2014;19:15584–610.

    Article  PubMed  Google Scholar 

  4. Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol. 2014;740:364–78.

    Article  CAS  PubMed  Google Scholar 

  5. Cavaletti G, Ceresa C, Nicolini G, Marmiroli P. Neuronal drug transporters in platinum drugs-induced peripheral neurotoxicity. Anticancer Res. 2014;34:483–6.

    CAS  PubMed  Google Scholar 

  6. Sprowl JA, Ness RA, Sparreboom A. Polymorphic transporters and platinum pharmacodynamics. Drug Metab Pharmacokinet. 2013;28:19–27.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  8. Efferth T, Volm M. Pharmacogenetics for individualized cancer chemotherapy. Pharmacol Ther. 2005;107:155–76.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  24. Featherstone C, Jackson SP. Ku, a DNA repair protein with multiple cellular functions? Mutat Res. 1999;434:3–15.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  28. Knepper MA, Wade JB, Terris J, Ecelbarger CA, Marples D, Mandon B, et al. Renal aquaporins. Kidney Int. 1996;49:1712–7.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  31. Holmes RP. The role of renal water channels in health and disease. Mol Asp Med. 2012;33:547–52.

    Article  CAS  Google Scholar 

Download references

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

Author information

Author notes

    Authors and Affiliations

    1. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China

      Juan Chen, Jiye Yin, Xiangping Li, Ting Zou, Chenyue Qian, Wei Zhang, Honghao Zhou & Zhaoqian Liu

    2. Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, People’s Republic of China

      Juan Chen, Jiye Yin, Xiangping Li, Ting Zou, Chenyue Qian, Wei Zhang, Honghao Zhou & Zhaoqian Liu

    3. Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, People’s Republic of China

      Juan Chen, Jiye Yin, Wei Zhang, Honghao Zhou & Zhaoqian Liu

    4. The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410014, People’s Republic of China

      Lin Wu & Ying Wang

    5. Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China

      Zhan Wang

    6. Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA

      Huihua Li

    7. Department of Radiotherapy, PLA 463 Hospital, Shenyang, 110042, People’s Republic of China

      Chuntian Li

    Authors
    1. Juan Chen
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Lin Wu
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Ying Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Jiye Yin
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Xiangping Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Zhan Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Huihua Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Ting Zou
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Chenyue Qian
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Chuntian Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. Wei Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    12. Honghao Zhou
      View author publications

      You can also search for this author in PubMed Google Scholar

    13. Zhaoqian Liu
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Zhaoqian Liu.

    Additional information

    Lin Wu and Ying Wang contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Chen, J., Wu, L., Wang, Y. et al. Effect of transporter and DNA repair gene polymorphisms to lung cancer chemotherapy toxicity. Tumor Biol. 37, 2275–2284 (2016). https://doi.org/10.1007/s13277-015-4048-0

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s13277-015-4048-0

    Keywords

    Search

    Navigation