Background: Telomeres play an important role in the maintenance of chromosomal stability. It has been previously reported that telomere length is shortened in hepatocellular carcinoma (HCC) compared to paired non-tumor tissue. However, most studies have been conducted in high-risk regions such as Asia. To date, no prior study has examined telomere length and HCC in the United States, a low risk region where HCC etiology may differ from that of high risk regions.
Methods: We measured telomere length in 127 paired tumor and non-tumor tissue samples from persons with HCC in Iowa, Hawaii and Connecticut. Formalin-fixed, paraffin-embedded tissues were collected at the time of diagnosis. Relative telomere length was measured by a monochrome multiplex quantitative PCR assay. The Wilcoxon signed-rank test was used to compare telomere length between tumor and paired non-tumor tissues. Cox proportional hazards modeling was used to estimate the association between telomere length and mortality, adjusting for age at diagnosis, sex, and tumor stage and size at diagnosis.
Results: Of the 127 pairs of samples, telomere length was shorter in the tumor in 88 pairs (69%), longer in the tumor in 33 pairs (26%) and the same length in the tumor and non-tumor tissue in 6 pairs (5%). Overall, the HCC tissues had statistically significantly shorter telomere length than their matched non-tumor tissues (p < 0.01). The proportion of pairs in which the tumor telomere was shorter than non-tumor was higher among those with localized stage tumors (81%) compared to those with regional or distant stage tumors (50%) (p < 0.01 after adjusting for age at diagnosis, sex, and source of the case). In addition, we observed a 119% higher risk of mortality (adjusted relative risk 2.19) among persons whose tumors had shorter telomeres than their non-tumor tissue, compared to persons whose tumors had longer telomeres; however, the confidence interval was relatively wide (0.94-5.12).
Conclusion: Using tissue samples from persons with HCC in the United States, we found that telomere length was shorter in tumor tissue compared to paired non-tumor tissue, especially among localized stage tumors. In addition, there was a suggestion that tumor telomere shortening might be associated with higher risk of mortality. Together, these results may provide insight into the role of biological mechanisms associated with telomere shortening and into the prognosis of HCC in lower risk populations.
Citation Format: Baiyu Yang, Fatma M. Shebl, Lawrence R. Sternberg, Andrew C. Warner, David E. Kleiner, Daniel C. Edelman, Allison Gomez, Casey L. Dagnall, Belynda D. Hicks, Sean F. Altekruse, Brenda Y. Hernandez, Charles F. Lynch, Paul S. Meltzer, Katherine A. McGlynn. Shortened telomere length in hepatocellular carcinoma in the United States. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 818.