DOI QR코드

DOI QR Code

Polymorphisms of TERT and CLPTM1L and the Risk of Hepatocellular Carcinoma in Chinese Males

  • Su, Ling-Yan (Department of Epidemiology, School of Public Health, China Medical University) ;
  • Li, Xue-Lian (Department of Epidemiology, School of Public Health, China Medical University) ;
  • Shen, Li (Department of Epidemiology, School of Public Health, China Medical University) ;
  • Zhang, Yue (Department of Epidemiology, School of Public Health, China Medical University) ;
  • Zhao, Meng-Meng (Department of Epidemiology, School of Public Health, China Medical University) ;
  • Yin, Zhi-Hua (Department of Epidemiology, School of Public Health, China Medical University) ;
  • Su, Hong-Ying (Department of Radiology, The First Affiliated Hospital of China Medical University) ;
  • Zhou, Bao-Sen (Department of Epidemiology, School of Public Health, China Medical University)
  • 발행 : 2014.10.23

초록

Background: Telomerase reverse transcriptase (TERT) and cleft lip and palate trans-membrane 1 like (CLPTM1L) genes located on chromosome 5p15.33 are known to influence the susceptibility to various cancers. Here, we examined the association of TERT and CLPTM1L single nucleotide polymorphisms (SNPs) with hepatocellular carcinoma (HCC). Materials and Methods: Genotyping of TERT SNP rs2736098 and CLPTM1L SNP rs401681 was performed using TaqMan allelic discrimination assays in a case-control study of 201 HCC cases and 210 controls in a Chinese male population. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression analyses. Results: Both the rs2736098 T allele of TERT and the rs401681 T allele of CLPTM1L were associated with a significantly increased risk of HCC (adjusted odds ratio [OR]=1.605, 95% confidence interval [CI]=1.164-2.213; adjusted OR=1.399, 95%CI=1.002-1.955, respectively). Individuals carrying both TERT and CLPTM1L risk genotypes had an even higher risk of HCC (adjusted OR=4.420, 95%CI= 2.319-8.425). The TERT rs2736098 T allele was also significantly associated with the level of the HCC clinical indicator alpha-fetoprotein (P=0.026). Conclusions: Our results show that genetic variants of TERT and CLPTM1L may contribute to HCC susceptibility in Chinese males.

키워드

참고문헌

  1. Artandi SE, DePinho RA (2010). Telomeres and telomerase in cancer. Carcinogenesis, 31, 9-18 https://doi.org/10.1093/carcin/bgp268
  2. Brechot C (2004). Pathogenesis of hepatitis B virus-related hepatocellular carcinoma: old and new paradigms. Gastroenterology, 127, 56-61. https://doi.org/10.1053/j.gastro.2004.09.016
  3. Choi JE, Kang HG, Jang JS, et al (2009). Polymorphisms in telomere maintenance genes and risk of lung cancer. Cancer Epidemiology Biomarkers and Prevention, 18, 2773-881. https://doi.org/10.1158/1055-9965.EPI-09-0323
  4. Cong YS, Wen J, Bacchetti S (1999). The human telomerase catalytic subunit hTERT: organization of the gene and characterization of the promoter. Hum Mol Genet, 8, 137-42 https://doi.org/10.1093/hmg/8.1.137
  5. Global cancer statistics (2011).
  6. Harley CB, Futcher AB, Greider CW (1990). Telomeres shorten during ageing of human fibroblasts. Nature, 345, 458-60. https://doi.org/10.1038/345458a0
  7. Hashem B. EI-Serag, K. Lenhard Rudolph (2007). Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology, 132, 2557-76. https://doi.org/10.1053/j.gastro.2007.04.061
  8. Iwama H, Ohyashiki K, Ohyashiki JH, et al (1998). Telomeric length and telomerase activity vary with age in peripheral blood cells obtained from normal individuals. Hum Genet, 102, 397-402. https://doi.org/10.1007/s004390050711
  9. James MA, Wen W, Wang Y, et al (2012). Functional characterization of CLPTM1L as a lung cancer risk candidate gene in the 5p15.33 locus. PLOS ONE, 7, 36116. https://doi.org/10.1371/journal.pone.0036116
  10. Luis E. Donate and Maria A.Blasco ( 2011). Telomeres in cancer and ageing. PhilosT roy Soc B, 366, 76-84 https://doi.org/10.1098/rstb.2010.0291
  11. Myneni AA, Chang SC, Niu R, et al (2013). Genetic polymorphisms of TERT and CLPTM1L and risk of lung cancer--a case-control study in a Chinese population. Lung Cancer, 80, 131-7. https://doi.org/10.1016/j.lungcan.2013.01.021
  12. Ni Z, Tao K, Chen G, et al (2012). CLPTM1L is overexpressed in lung cancer and associated with apoptosis. PLOS ONE, 7, 52598. https://doi.org/10.1371/journal.pone.0052598
  13. Rafnar T, Sulem P, Stacey SN, et al (2009). Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat Genet, 41, 221-7. https://doi.org/10.1038/ng.296
  14. Rudolph KL, Millard M, Bosenberg MW, DePinho RA (2001). . Telomere dysfunction and evolution of intestinal carcinoma in mice and humans. Nat Genet, 28, 155-9. https://doi.org/10.1038/88871
  15. Sambrook J (1989). Molecular cloning: a laboratory manual. cold spring harbor laboratory press, New York, NY.
  16. Shen Q, Fan J, Yang XR, et al (2012). Serum DKK1 as a protein biomarker for the diagnosis of hepatocellular carcinoma: a large-scale, multicentre study. The Lancet Oncology, 13, 817-26. https://doi.org/10.1016/S1470-2045(12)70233-4
  17. Takakura M, Kyo S, Kanaya T, et al (1999). Cloning of human telomerase catalytic subunit (hTERT) gene promoter andidentification of proximal core promoter sequences essential for transcriptional activation in immortalized and cancer cells. Cancer Res, 59, 551-7
  18. Tanabe KK, Lemoine A, Finkelstein DM, et al (2008). Epidermal growth factor gene functional polymorphism and the risk of hepatocellular carcinoma in patients with cirrhosis. JAMA, 299, 53-60.
  19. Wang Y, Broderick P, Webb E, et al (2008). Common 5p15.33 and 6p21.33 variants influence lung cancer risk. Nature Genetics. 40, 1407-9. https://doi.org/10.1038/ng.273
  20. Wick M, Zubov D, Hagen G (1999). Genomic organization and promoter characterization of the gene encoding the human telomerase reverse transcriptase (hTERT). Gene, 232, 97-106. https://doi.org/10.1016/S0378-1119(99)00108-0
  21. Yamamoto K, Okamoto A, Isonishi S, Ochiai K, Ohtake Y (2001). A novel gene, CRR9, which was up-regulated in CDDP-resistant ovarian tumor cell line, was associated with apoptosis. Biochem Bioph Res Co, 280, 1148-54 https://doi.org/10.1006/bbrc.2001.4250
  22. YoungNS (2010). Telomere biology and telomere diseases: implications for practice and research. American Society of Hematology Education Program, 2010, 30-35. https://doi.org/10.1182/asheducation-2010.1.30
  23. Zhang C, Tian YP, Wang Y, et al (2012). hTERT rs2736098 genetic variants and susceptibility of hepatocellular carcinoma in the Chinese population: a case-control study. Hepatobiliary and Pancreatic diseases international: HBPDINT, 12, 74-9.
  24. Zhao Y, Chen G, Zhao Y, et al (2012). Fine-mapping of a region of chromosome 5p15.33 (TERT-CLPTM1L) suggests a novel locus in TERT and aCLPTM1L haplotype are associated with glioma susceptibility in a Chinese population. Int J cancer, 131, 1569-76. https://doi.org/10.1002/ijc.27417

피인용 문헌

  1. ) Gene Variations and Susceptibility of Colorectal Cancer vol.19, pp.12, 2015, https://doi.org/10.1089/gtmb.2015.0150
  2. Telomere Maintenance Mechanisms in Cancer vol.9, pp.5, 2018, https://doi.org/10.3390/genes9050241
  3. Association Between TERT rs2736098 Polymorphisms and Cancer Risk-A Meta-Analysis vol.9, pp.1664-042X, 2018, https://doi.org/10.3389/fphys.2018.00377