Association of telomere length in peripheral leukocytes with chronic hepatitis B and hepatocellular carcinoma.
OBJECTIVE
Telomere plays a critical role in the maintenance of genomic stability in eukaryotic chromosomes. More and more findings have shown that alteration in telomere length may involve in normal somatic cells and some diseases, however, whether the telomere length is associated with the development and/or progression of hepatic diseases remains poorly understood.


METHODS
A case-control study was employed to illustrate the correlation of relative telomere length (RTL) with chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC). In this study, 152 patients with HCC, 212 patients with CHB, and 184 healthy controls were recruited. Genomic deoxyribonucleic acid (DNA) was extracted from the peripheral blood leukocytes, and fluorescence quantitative polymerase chain reaction (FQ-PCR) was used to detect telomere repeated numbers and 36B4 copy numbers. The RTL was calculated by telomere repeat copy number to single-copy gene number ratio in each sample compared with a reference DNA sample.


RESULTS
We found that the RTL in HCC group was the longest, followed by CHB group, and healthy control group was the shortest, showing significant statistical differences. When participants were categorized into longer and shorter group according to medium value in healthy controls, individuals who had longer RTL had a significant increased risk of CHB (odds ratio [OR]: 1.83, 95% confidence interval [CI]: 1.22-2.73) when the healthy control was used as the reference groups; furthermore, longer RTL also showed higher incidence of HCC (OR: 3.22, 95% CI: 2.01-5.17; OR: 1.58, 95% CI:1.03-2.41) when healthy control and CHB were used as the reference groups, respectively. When participants were categorized further into 4 groups according to quartile values of RTL in healthy controls, it showed that the longest RTL was also associated with an increased risk of CHB (OR: 2.09, 95% CI: 1.17-3.74) and HCC (OR: 4.31, 95% CI: 2.18-8.52; OR: 2.86, 95% CI: 1.53-5.34) when control and control/CHB group were used as the reference groups, respectively.


CONCLUSIONS
Our results suggest that the alteration of telomere length in peripheral leukocytes might be involved in the hepatitis B virus infection and HCC events, and RTL might be a potential useful predictor of CHB and HCC.
aDepartment of Laboratory Medicine, Affiliated Hospital of North Sichuan Medical College bTranslational Medicine Research Center, North Sichuan Medical College, Nanchong, Sichuan, China.
Qiang
Q
Ma
Jiajing
J
Cai
Yan
Y
Cai
Yuan
Y
Xu
Fan
F
Chang
Lei
L
Xu
Guoyuan
G
Zhang
Xiaolan
X
Guo
D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D004247:DNA / Q000097:blood; D005260:Female; D019694:Hepatitis B, Chronic / Q000097:blood / Q000150:complications / Q000235:genetics*; D006801:Humans; D015994:Incidence; D007962:Leukocytes; D008113:Liver Neoplasms / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors; D016615:Telomere / Q000235:genetics*
D004247:DNA
Nucleic Acids Res. 2009 Feb;37(3):e21
19129229
Sci Rep. 2014 Nov 17;4:7073
25399515
Acta Virol. 2013;57(4):389-96
24294951
Med Oncol. 2012 Jun;29(2):893-8
21359861
Oncogene. 2002 Jan 21;21(4):619-26
11850787
PLoS One. 2014 Feb 03;9(2):e86063
24498269
Cancer Res. 2014 Aug 1;74(15):4090-8
24853549
Int J Cancer. 2015 Mar 1;136(5):E351-8
25066524
Cancer Epidemiol Biomarkers Prev. 2014 Nov;23(11):2439-46
25234236
Cancer Lett. 2014 Apr 10;345(2):216-22
23981576
Haematologica. 2015 Jan;100(1):49-54
25304614
Cancer. 2011 Sep 15;117(18):4247-56
21387275
Hepatology. 2004 Jul;40(1):80-6
15239089
Physiol Res. 2014;63 Suppl 3:S343-50
25428739
Cancer Epidemiol Biomarkers Prev. 2014 Nov;23(11):2603-6
25159293
Liver Int. 2009 Sep;29(8):1162-70
19627485
J Lab Clin Med. 2005 Feb;145(2):98-104
15746653
Biochem Biophys Res Commun. 2014 May 2;447(2):358-63
24732358
Free Radic Biol Med. 2008 Feb 1;44(3):235-46
18021748
Nat Rev Cancer. 2001 Dec;1(3):203-13
11902575
Hepatology. 2004 Aug;40(2):276-83
15368430
Exp Cell Res. 2008 Jun 10;314(9):1973-9
18448098
Mod Pathol. 2009 Aug;22(8):1121-31
19465904
Virus Genes. 2010 Apr;40(2):174-82
20107884
J Thorac Oncol. 2015 Feb;10(2):302-8
25299235
Mech Ageing Dev. 2008 Jan-Feb;129(1-2):27-34
18054990
Mech Ageing Dev. 2001 May 31;122(7):695-712
11322993
Liver Int. 2012 Sep;32(8):1233-41
22471856
Eur J Cancer. 2012 May;48(7):1014-22
22444598
Mol Oncol. 2015 Mar;9(3):727-39
25515040
J Thorac Dis. 2014 Nov;6(11):1532-47
25478195
Semin Cancer Biol. 2011 Dec;21(6):349-53
22015685
Br J Cancer. 2015 Feb 17;112(4):769-76
25562437
J Clin Gastroenterol. 2004 Nov-Dec;38(10 Suppl 3):S158-68
15602165
Int J Biochem Cell Biol. 2005 May;37(5):1000-13
15743674
Nucleic Acids Res. 2002 May 15;30(10):e47
12000852