Tumor Biology

, Volume 35, Issue 9, pp 8679–8683 | Cite as

The programmed cell death 6 interacting protein insertion/deletion polymorphism is associated with non-small cell lung cancer risk in a Chinese Han population

  • Shu-Guang Liu
  • Shuang-hu Yuan
  • Hui-Yong Wu
  • Cheng-Suo Huang
  • Jie Liu
Research Article


It has been proposed that genetic factors contribute to the susceptibility of non-small cell lung cancer (NSCLC). The programmed cell death 6 interacting protein (PDCD6IP) encodes for a protein that has been known to bind to the products of the PDCD6 gene, a required protein in apoptosis. The aim of this study is to investigate the relationship between PDCD6IP insertion/deletion (I/D) polymorphism (rs28381975) and NSCLC risk in a Chinese population. A population-based case–control study was conducted in 449 NSCLC patients and 512 cancer-free controls. The genotype of the PDCD6IP gene was determined by using a polymerase chain reaction assay. The promoter activity was analyzed by luciferase reporter assay in A549 and H1299 cells. Statistically significant difference was observed when the patients and controls were compared according to ID + II versus DD (OR = 1.72, 95 % CI 1.29–2.31, P < 0.01). The I allele was significantly associated with NSCLC risk (OR = 1.41, 95 % CI 1.18–1.69, P < 0.01). Compared to TNM stage I + II, PDCD6IP I/D polymorphism significantly increased advanced NSCLC risk (OR = 2.06, 95 % CI 1.30–3.26, P < 0.01). Promoter reporter structures carrying the I allele displayed significantly higher promoter activity than the D allele in A549 and H1299 cells (P = 0.001). The results from this study suggested that PDCD6IP I/D polymorphism was potentially related to NSCLC susceptibility in Chinese Han population.


Non-small cell lung cancer Programmed cell death 6 interacting protein Polymorphism Genetics 


Conflicts of interest



  1. 1.
    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30.CrossRefPubMedGoogle Scholar
  2. 2.
    Rudd MF, Webb EL, Matakidou A, Sellick GS, Williams RD, Bridle H, et al. Variants in the GH-IGF axis confer susceptibility to lung cancer. Genome Res. 2006;16:693–701.PubMedCentralCrossRefPubMedGoogle Scholar
  3. 3.
    Wang Y, Broderick P, Matakidou A, Eisen T, Houlston RS. Role of 5p15.33 (TERT-CLPTM1L), 6p21.33 and 15q25.1 (CHRNA5-CHRNA3) variation and lung cancer risk in never-smokers. Carcinogenesis. 2010;31:234–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Young RP, Hopkins RJ, Whittington CF, Hay BA, Epton MJ, Gamble GD. Individual and cumulative effects of GWAS susceptibility loci in lung cancer: associations after sub-phenotyping for COPD. PLoS One. 2011;6:e16476.PubMedCentralCrossRefPubMedGoogle Scholar
  5. 5.
    Missotten M, Nichols A, Rieger K, Sadoul R. Alix, a novel mouse protein undergoing calcium-dependent interaction with the apoptosis-linked-gene 2 (ALG-2) protein. Cell Death Differ. 1999;6:124–9.CrossRefPubMedGoogle Scholar
  6. 6.
    Vito P, Pellegrini L, Guiet C, D’Adamio L. Cloning of AIP1, a novel protein that associates with the apoptosis-linked gene ALG-2 in a Ca2+-dependent reaction. J Biol Chem. 1999;274:1533–40.CrossRefPubMedGoogle Scholar
  7. 7.
    Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972;26:239–57.PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Kerr JF, Winterford CM, Harmon BV. Apoptosis. Its significance in cancer and cancer therapy. Cancer. 1994;73:2013–26.CrossRefPubMedGoogle Scholar
  9. 9.
    Kaiser HE, Bodey B. The role of apoptosis in normal ontogenesis and solid human neoplasms. In Vivo. 2000;14:789–803.PubMedGoogle Scholar
  10. 10.
    Verfaillie T, Garg AD, Agostinis P. Targeting ER stress induced apoptosis and inflammation in cancer. Cancer Lett. 2013;332:249–64.CrossRefPubMedGoogle Scholar
  11. 11.
    Wong RS. Apoptosis in cancer: from pathogenesis to treatment. J Exp Clin Cancer Res. 2011;30:87.PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    Yu Q, Zhou C, Wang J, Chen L, Zheng S, Zhang J. A functional insertion/deletion polymorphism in the promoter of PDCD6IP is associated with the susceptibility of hepatocellular carcinoma in a Chinese population. DNA Cell Biol. 2013;32:451–7.CrossRefPubMedGoogle Scholar
  13. 13.
    Zhou C, Luo Q, Qing Y, Lin X, Zhan Y, Ouyang M. Association between MPO 463G>A polymorphism and risk of lung cancer: a meta-analysis. Tumour Biol. 2013;34:3449–55.CrossRefPubMedGoogle Scholar
  14. 14.
    Wang L, Chen Z, Wang Y, Chang D, Su L, Guo Y, et al. The association of c.1471G>A genetic polymorphism in XRCC1 gene with lung cancer susceptibility in Chinese Han population. Tumour Biol. 2014.Google Scholar
  15. 15.
    Liu H, Li HY, Chen HJ, Huang YJ, Zhang S, Wang J. EPHX1 A139G polymorphism and lung cancer risk: a meta-analysis. Tumour Biol. 2013;34:155–63.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Shu-Guang Liu
    • 1
  • Shuang-hu Yuan
    • 2
  • Hui-Yong Wu
    • 1
  • Cheng-Suo Huang
    • 3
  • Jie Liu
    • 1
  1. 1.Department of SurgeryShandong Cancer Hospital and InstituteJinanChina
  2. 2.Department of RadiotherapyShandong Cancer Hospital and InstituteJinanChina
  3. 3.Department of ChemotherapyShandong Cancer Hospital and InstituteJinanChina

Personalised recommendations