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Role of polymorphic XRCC6 (Ku70)/XRCC7 (DNA-PKcs) genes towards susceptibility and prognosis of lung cancer patients undergoing platinum based doublet chemotherapy

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Abstract

The DNA repair genes XRCC6 and XRCC7 formed an integral part of double strand break repair (DSBR) pathway. The two genes are thought to play an important role in the repair of lethal double strand damage on DNA. Polymorphic DSBR genes are studied to effect genomic stability. We intend to explore the association of DSBR genes i.e. XRCC6 and XRCC7 with susceptibility and survival in North Indian lung cancer patients. DNA isolation and genotyping was done for 320 controls and 330 lung cancer cases enrolled in the study. Each and every lung cancer study subjects were made a telephonic call and were followed for their health after administration of chemotherapy. Statistical analysis for susceptibility was done using logistic regression analysis. Survival analysis was done using Kaplan–Meier followed by Cox-regression. Small cell lung cancer (SCLC) subtype posed an amplified risk towards lung cancer in case of XRCC7 6721G>T (OR = 4.11, p = 0.0040). Gene-environment interaction analysis revealed that non-smokers with heterozygous genotype (CG) in case of XRCC6 61C>G showed a strong protective effect (OR = 0.38, p = 0.01) towards lung cancer. Survival analysis revealed poor prognosis in case of XRCC6 61C>G SCLC subtype. XRCC6 and XRCC7 were not involved in overall susceptibility and survival. However, in case of XRCC7 6721G>T subjects with SCLC subtype showed an increased susceptibility while poor prognosis in case of XRCC6 61C>G.

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References

  1. Singh A, Singh N, Behera D, Sharma S (2016) Association and multiple interaction analysis among five XRCC1 polymorphic variants in modulating lung cancer risk in North Indian population. DNA Repair 47:30–41

    Article  PubMed  CAS  Google Scholar 

  2. Evdokimova V, Gandhi M, Rayapureddi J, Stringer JR, Nikiforov YE (2012) Formation of carcinogenic chromosomal rearrangements in human thyroid cells after induction of double-strand DNA breaks by restriction endonucleases. Endocr Relat Cancer 19(3):271–281

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Jia J, Ren J, Yan D, Xiao L, Sun R (2015) Association between the XRCC6 polymorphisms and cancer risks: a systematic review and meta-analysis. Medicine 94(1)

  4. Jackson SP (2002) Sensing and repairing double strand breaks. Carcinogenesis 23(5):687–696

    Article  PubMed  CAS  Google Scholar 

  5. Kanaar R, Hoeijmakers JH, van Gent DC (1998) Molecular mechanisms of DNA double-strand break repair. Trends Cell Biol 8:483–489

    Article  PubMed  CAS  Google Scholar 

  6. Karran P (2000) DNA double strand break repair in mammalian cells. Curr Opin Genet Dev 10:144–150

    Article  PubMed  CAS  Google Scholar 

  7. Wang S-Y, Peng L, Li C-P, Li A-P, Zhou J-W, Zhang Z-D, Liu Q-Z (2008) Genetic variants of the XRCC7 gene involved in DNA repair and risk of human bladder cancer. Int J Urol 15:534–539

    Article  PubMed  CAS  Google Scholar 

  8. Spitz MR, Wei Q, Dong Q, Amos CI, Wu X (2003) Genetic susceptibility to lung cancer: the role of DNA damage and repair. Cancer Epidemiol Biomark Prev 12(8):689–698

    CAS  Google Scholar 

  9. Tseng R-C, Hsieh F-J, Shih C-M, Hsu H-S, Chen C-Y, Wang Y-C (2009) Lung cancer susceptibility and prognosis associated with polymorphisms in the nonhomologous end-joining pathway genes: a multiple genotype-phenotype study. Cancer 115:2939–2948

    Article  PubMed  CAS  Google Scholar 

  10. He W, Luo S, Huang T, Ren J, Wu X, Shao J, Zhu Q (2012) The Ku70 – 1310C/G promoter polymorphism is associated with breast cancer susceptibility in Chinese Han population. Mol Biol Rep 39(1):577–583

    Article  PubMed  CAS  Google Scholar 

  11. Nasiri M, Saadat I, Omidvari S, Saadat M (2012) Genetic variation in DNA repair gene XRCC7 (G6721T) and susceptibility to breast cancer. J Gene 505(1):195–197

    Article  CAS  Google Scholar 

  12. Wang L-E, Bondy ML, Shen H, El-Zein R, Aldape K, Cao Y, Pudavalli V, Levin VA, Yung WKA, Wei Q (2004) Polymorphisms of DNA repair genes and risk of glioma. Cancer Res 64:5560–5563

    Article  PubMed  CAS  Google Scholar 

  13. Hirata H, Hinoda Y, Matsuyama H, Tanaka Y, Okayama N, Suehiro Y, Zhao H, Urakami S, Kawamoto K, Kawakami T, Igawa M, Naito K, Dahiya R (2006) Polymorphisms of DNA repair genes are associated with renal cell carcinoma. Biochem Biophy Res Commun 342:1058–1062

    Article  CAS  Google Scholar 

  14. Hsieh Y-H, Chang W-S, Tsai C-W, Tsai J-P, Hsu C-M, Jeng L-B, Bau D-T (2015) DNA double-strand break repair gene XRCC7 genotypes were associated with hepatocellular carcinoma risk in Taiwanese males and alcohol drinkers. Tumor Biol. https://doi.org/10.1007/s13277-014-2934-5

    Article  Google Scholar 

  15. Li R, Yang Y, An Y, Zhou Y, Liu Y, Yu Q, Lu D, Wang H, Jin L, Zhou W, Qian J, Shugart YY (2011) Genetic polymorphisms in DNA double-strand break repair genes XRCC5, XRCC6 and susceptibility to hepatocellular carcinoma. Carcinogenesis 32(4):530–536

    Article  PubMed  CAS  Google Scholar 

  16. Yang M-D, Wang H-C, Chang W-S, Tsai C-W, Bau D-T (2011) Genetic polymorphisms of DNA double strand break gene Ku70 and gastric cancer in Taiwan. BMC Cancer 11:174

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Peng L, Li CP, Li AP, Zhou JW, Zhang ZD, Liu QZ (2008) Genetic variants of the XRCC7 gene involved in DNA repair and risk of human bladder cancer. Int J Urol 15(6):534–539

    Article  PubMed  CAS  Google Scholar 

  18. Sharma N, Singh A, Singh N, Behera D, Sharma S (2015) Genetic polymorphisms in GSTM1, GSTT1 and GSTP1 genes and risk of lung cancer in a North Indian population. Cancer Epidemiol. 39:947–955

    Article  PubMed  Google Scholar 

  19. Jahantigh D, Salimi S, Mousavi M, Moossavi M, Mohammadoo-Khorasani M, Narooei-nejad M, Sandoughi M (2015) Association between functional polymorphisms of DNA double-strand breaks in repair genes XRCC5, XRCC6 and XRCC7 with the risk of systemic lupus erythematosus in South East Iran. DNA Cell Biol 34:1–7

    Article  CAS  Google Scholar 

  20. Chang W-S, Ke H-L, Tsai C-W, Lien C-S, Liao W-L, Lin H-H, Lee M-H, Wu H-C, Chang C-H, Chen C-C, Lee H-Z, Bau D-T (2012) The role of XRCC6 T-991C functional polymorphism in renal cell carcinoma. Anticancer Res 32:3855–3860

    PubMed  CAS  Google Scholar 

  21. Wang G, Wang S, Shen Q, Yin S, Li C, Li A, Li J, Zhou J, Liua Q (2009) Polymorphisms in XRCC5, XRCC6, XRCC7 genes are involved inDNA double-strand breaks (DSBs) repair associated with the risk of acute myeloid leukemia (AML) in Chinese population. J Nanjing Med Univ 23(2):93–99

    Article  CAS  Google Scholar 

  22. Jia J, Ren J, Yan D, Xiao L, Sun R (2015) Association between the XRCC6 polymorphisms and cancer risks: a systematic review and meta-analysis. Medicine

  23. Li T, Suo Q, He D, Du W, Yang M, Fan X, Liu J (2012) Esophageal cancer risk is associated with polymorphisms of DNA repair genes MSH2 and WRN in Chinese population. J Thorac Oncol 7(2):448–452

    Article  PubMed  CAS  Google Scholar 

  24. Hsia TC, Liu CJ, Chu CC, Hang LW, Chang WS, Tsai CW, Wu CI, Lien CS, Liao WL, Ho CY, Bau DT (2012) Association of DNA double-strand break gene XRCC6 genotypes and lung cancer in Taiwan. Anticancer Res 32(3):1015–1020

    PubMed  CAS  Google Scholar 

  25. Beggs AD, Domingo E, McGregor M (2012) Loss of expression of the double strand break repair protein ATM is associated with worse prognosis in colorectal cancer and loss of Ku70 expression is associated with CIN. Oncotarget 3:1348–1355

    Article  PubMed  PubMed Central  Google Scholar 

  26. Mandal RK, Kapoor R, Mittal RD (2010) Polymorphic variants of DNA repair gene XRCC3 and XRCC7 and risk of prostate cancer: a study from North Indian population. DNA Cell Biol 29(11):669–674

    Article  PubMed  CAS  Google Scholar 

  27. Zhi Y, Yu J, Liu Y, Wei Q, Yuan F, Zhou X, Song B, Chen Z, Yang J (2012) Interaction between polymorphisms of DNA repair genes significantly modulated bladder cancer risk. Int J Med Sci 9(6):498–505

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Hu Z, Liu H, Wang H, Miao R, Sun W, Jin G, Wang Y, Ma H, Jin L, Wei Q, Lu D, Huang W, Shen H (2008) Tagging single nucleotide polymorphisms in phosphoinositide-3-kinase–related protein kinase genes involved in DNA damage “checkpoints” and lung cancer susceptibility. Clin Cancer 14(9):2887–2891

    Article  CAS  Google Scholar 

  29. Hsia TC, Chang WS, Chen WC, Liang SJ, Tu CY, Chen HJ, Liang JA, Tsai CW, Hsu CM, Tsai CH, Bau DT (2014) Genotype of DNA double-strand break repair gene XRCC7 is associated with lung cancer risk in Taiwan males and smokers. Anticancer Res 34(12):7001–7005

    PubMed  CAS  Google Scholar 

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Acknowledgements

We would like to express our gratitude to all the subjects who participated in this current study. This work was supported by grant from the Indian Council of Medical Research, New Delhi, India (Grant No. 5/13/126/2011/NCD-III).

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Authors and Affiliations

  1. Department of Biotechnology, Thapar University, Patiala, Punjab, 147002, India

    Amrita Singh & Siddharth Sharma

  2. Department of Pulmonary Medicine, Post Graduate Institute of Medical Education and Research (PGIMER), Sector 14, Chandigarh, India

    Navneet Singh & Digambar Behera

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  1. Amrita Singh
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  2. Navneet Singh
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  4. Siddharth Sharma
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Correspondence to Siddharth Sharma.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Singh, A., Singh, N., Behera, D. et al. Role of polymorphic XRCC6 (Ku70)/XRCC7 (DNA-PKcs) genes towards susceptibility and prognosis of lung cancer patients undergoing platinum based doublet chemotherapy. Mol Biol Rep 45, 253–261 (2018). https://doi.org/10.1007/s11033-018-4158-z

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  • DOI: https://doi.org/10.1007/s11033-018-4158-z

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