Clinical and Experimental Medicine

, Volume 15, Issue 4, pp 477–482 | Cite as

Association between CLPTM1L–TERT rs401681 polymorphism and risk of pancreatic cancer: a meta-analysis

  • Cheng-Li LiuEmail author
  • Xiao-Xia Zang
  • Cheng Wang
  • Ya-Lin Kong
  • Hui Zhang
  • Hong-Yi Zhang
Original Article


Telomere biology plays a critical and complex role in the initiation and progression of cancer. Several recent studies have provided evidence that rs401681 polymorphisms in intronic region of cleft lip and palate trans-membrane 1-like (CLPTM1L) gene sequence are associated with pancreatic cancer (PC) development, but a comprehensive synopsis is not available. We performed a meta-analysis of 6 case–control studies that included 8,253 pancreatic cancer cases and 37,646 case-free controls. We assessed the strength of the association, using odds ratios (ORs) with 95 % confidence intervals (CIs). Overall, this meta-analysis showed that rs401681 allele T was associated with a significantly increased PC risk (OR = 1.17, 95 % CI = 1.12–1.22, P heterpgeneity = 0.596 and I 2 = 0). Similarly, in the subgroup analysis by ethnicity, a significantly increased risk was found among Asians (OR = 1.15, 95 % CI = 1.07–1.24, P heterpgeneity = 0.297 and I 2 = 8.0 %) and among Caucasian (OR = 1.13, 95 % CI = 1.02–1.26, P heterpgeneity = 0.385 and I 2 = 0). No publication bias was found in the present study. This meta-analysis suggests that T allele of CLPTM1L–telomerase reverse transcriptase rs401681 polymorphism is associated with an increased PC risk, especially among Chinese. Further large and well-designed studies are needed to confirm this association.


Pancreatic cancer Telomerase reverse transcriptase (TERT) Cleft lip and palate trans-membrane 1-like (CLPTM1L) gene Polymorphism 


Conflict of interest



  1. 1.
    Maisonneuve P, Lowenfels AB. Epidemiology of pancreatic cancer: an update. Dig Dis. 2010;28:645–56.CrossRefPubMedGoogle Scholar
  2. 2.
    Bednar F, Simeone DM. Pancreatic cancer stem cell biology and its therapeutic implications. J Gastroenterol. 2011;46:1345–52.CrossRefPubMedGoogle Scholar
  3. 3.
    Hansel DE, Kern SE, Hruban RH. Molecular pathogenesis of pancreatic cancer. Annu Rev Genomics Hum Genet. 2003;4:237–56.CrossRefPubMedGoogle Scholar
  4. 4.
    Vaccaro V, Gelibter A, Bria E, et al. Molecular and genetic bases of pancreatic cancer. Curr Drug Targets. 2012;13:731–43.CrossRefPubMedGoogle Scholar
  5. 5.
    Nakao M, Hosono S, Ito H, et al. Selected polymorphisms of base excision repair genes and pancreatic cancer risk in Japanese. J Epidemiol. 2012;22:477–83.CrossRefPubMedGoogle Scholar
  6. 6.
    Krejs GJ. Pancreatic cancer: epidemiology and risk factors. Dig Dis. 2010;28:355–8.CrossRefPubMedGoogle Scholar
  7. 7.
    Luo J, Iwasaki M, Inoue M, et al. Body mass index, physical activity and the risk of pancreatic cancer in relation to smoking status and history of diabetes: a large-scale population-based cohort study in Japan—the JPHC study. Cancer Causes Control. 2007;18:603–12.CrossRefPubMedGoogle Scholar
  8. 8.
    Wang Y, Broderick P, Webb E, et al. Common 5p15.33 and 6p21.33 variants influence lung cancer risk. Nat Genet. 2008;40:1407–9.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Rafnar T, Sulem P, Stacey SN, et al. Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat Genet. 2009;41:221–7.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Stacey SN, Sulem P, Masson G, et al. New common variants affecting susceptibility to basal cell carcinoma. Nat Genet. 2009;41:909–14.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Petersen GM, Amundadottir L, Fuchs CS, et al. A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat Genet. 2010;42:224–8.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Shay JW, Wright WE. Role of telomeres and telomerase in cancer. Semin Cancer Biol. 2011;21:349–53.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Gomez DE, Armando RG, Farina HG, et al. Telomere structure and telomerase in health and disease (review). Int J Oncol. 2012;41:1561–9.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Yamamoto K, Okamoto A, Isonishi S, Ochiai K, Ohtake Y. A novel gene, CRR9, which was up-regulated in CDDP-resistant ovarian tumor cell line, was associated with apoptosis. Biochem Biophys Res Commun. 2001;280:1148–54.CrossRefPubMedGoogle Scholar
  15. 15.
    Wu C, Miao X, Huang L, et al. Genome-wide association study identifies five loci associated with susceptibility to pancreatic cancer in Chinese populations. Nat Genet. 2012;44:62–6.CrossRefGoogle Scholar
  16. 16.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.CrossRefPubMedGoogle Scholar
  17. 17.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Harsha HC, Kandasamy K, Ranganathan P, et al. A compendium of potential biomarkers of pancreatic cancer. PLoS Med. 2009;6:e1000046.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Bauer AS, Keller A, Costello E, et al. Diagnosis of pancreatic ductal adenocarcinoma and chronic pancreatitis by measurement of microRNA abundance in blood and tissue. PLoS One. 2012;7:e34151.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Yachida S, Iacobuzio-Donahue CA. Evolution and dynamics of pancreatic cancer progression. Oncogene. 2013;32:5253–60.CrossRefPubMedGoogle Scholar
  22. 22.
    Iacobuzio-Donahue CA, Velculescu VE, Wolfgang CL, Hruban RH. Genetic basis of pancreas cancer development and progression: insights from whole-exome and whole-genome sequencing. Clin Cancer Res. 2012;18:4257–65.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    McGrath M, Wong JY, Michaud D, Hunter DJ, De Vivo I. Telomere length, cigarette smoking, and bladder cancer risk in men and women. Cancer Epidemiol Biomarkers Prev. 2007;16:815–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Jang JS, Choi YY, Lee WK, et al. Telomere length and the risk of lung cancer. Cancer Sci. 2008;99:1385–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Risques RA, Vaughan TL, Li X, et al. Leukocyte telomere length predicts cancer risk in Barrett’s esophagus. Cancer Epidemiol Biomarkers Prev. 2007;16(26):49–55.Google Scholar
  26. 26.
    Hou L, Savage SA, Blaser MJ, et al. Telomere length in peripheral leukocyte DNA and gastric cancer risk. Cancer Epidemiol Biomarkers Prev. 2009;18:3103–9.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Willeit P, Willeit J, Mayr A, et al. Telomere length and risk of incident cancer and cancer mortality. JAMA. 2010;304:69–75.CrossRefPubMedGoogle Scholar
  28. 28.
    Willeit P, Willeit J, Kloss-Brandstatter A, Kronenberg F, Kiechl S. Fifteen-year follow-up of association between telomere length and incident cancer and cancer mortality. JAMA. 2011;306:42–4.CrossRefPubMedGoogle Scholar
  29. 29.
    Kobitsu K, Tsutsumi M, Tsujiuchi T, et al. Shortened telomere length and increased telomerase activity in hamster pancreatic duct adenocarcinomas and cell lines. Mol Carcinog. 1997;1(8):153–9.CrossRefGoogle Scholar
  30. 30.
    Kuniyasu H, Kitadai Y, Mieno H, Yasui W. Helicobactor pylori infection is closely associated with telomere reduction in gastric mucosa. Oncology. 2003;65:275–82.CrossRefPubMedGoogle Scholar
  31. 31.
    van Heek NT, Meeker AK, Kern SE, et al. Telomere shortening is nearly universal in pancreatic intraepithelial neoplasia. Am J Pathol. 2002;161:1541–7.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Rizzato C, Campa D, Giese N, et al. Pancreatic cancer susceptibility loci and their role in survival. PLoS One. 2011;6:e27921.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Willis JA, Olson SH, Orlow I, et al. A replication study and genome-wide scan of single-nucleotide polymorphisms associated with pancreatic cancer risk and overall survival. Clin Cancer Res. 2012;18:3942–51.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Liu C, Wang Y, Huang H, Wang C, Zhang H, Kong Y, Zhang H. Association between CLPTM1L–TERT rs401681 polymorphism and pancreatic cancer risk among Chinese Han population. Tumour Biol. 2014;35(6):5453–7. doi: 10.1007/s13277-014-1711-9.

Copyright information

© Springer-Verlag Italia 2014

Authors and Affiliations

  • Cheng-Li Liu
    • 1
    Email author
  • Xiao-Xia Zang
    • 2
  • Cheng Wang
    • 1
  • Ya-Lin Kong
    • 1
  • Hui Zhang
    • 1
  • Hong-Yi Zhang
    • 1
  1. 1.Department of Hepatobiliary SurgeryAir Force General Hospital of PLABeijingPeople’s Republic of China
  2. 2.Department of StomatologyAir Force General Hospital of PLABeijingPeople’s Republic of China

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