Telomere attrition and decreased Fetuin A levels indicate accelerated biological ageing and are implicated in the pathogenesis of colorectal cancer

Maxwell, F., McGlynn, L.M., Muir, H.C., Talwar, D., Benzeval, M., Robertson, T., Roxburgh, C.S., McMillan, D. , Horgan, P.G. and Shiels, P. (2011) Telomere attrition and decreased Fetuin A levels indicate accelerated biological ageing and are implicated in the pathogenesis of colorectal cancer. Clinical Cancer Research, 17(17), pp. 5573-5581. (doi: 10.1158/1078-0432.CCR-10-3271)

Abstract

Purpose Increasing chronological age is a risk factor for many types of cancer including colorectal. An understanding of the biology of ageing and factors which regulate it may provide insight into cancer pathogenesis. The role of telomere biology in both the cancer and ageing process could prove useful in this regard. Experimental Design Using quantitative-PCR we determined telomere length in the peripheral blood leucocytes of 64 colorectal cancer patients and 1348 controls. We also measured telomere length in 32 colorectal tumor samples and matched normal tissue. We aimed to assess if telomere lengths were reflected in circulating mediators of inflammation and redox control factors, including fetuin-A a circulating modulator of calcium homeostasis. Results Colorectal cancer patients had shorter telomeres (adjusted mean RelT/S=0.61) compared with chronologically older controls (mean age 75, adjusted mean RelT/S=0.70) (ANCOVA, p=0.004). Telomere length in tumour tissue (median=0.43, IQR=0.40) was significantly shorter than adjacent normal tissue (median=0.65, IQR=0.28) (p=0.004). Patients with low fetuin-A levels were shown to have significantly shorter telomeres (p=0.041). Patients with rectal tumors had significantly higher levels of fetuin-A than those with colonic tumors (p=0.045). Conclusions We have observed that patients with colorectal cancer display clear evidence of telomere attrition compared with controls. This is congruent with accelerated biological ageing in the pathogenesis of colorectal cancer. An imbalance in redox control mechanisms and calcium homeostasis may be a contributing factor to telomere dynamics in our patients. Furthermore, fetuin-A levels can be used distinguish between colon and rectal cancers.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Horgan, Professor Paul and Robertson, Dr Anthony and McMillan, Professor Donald and McGlynn, Dr Liane and Roxburgh, Professor Campbell and Maxwell, Mr Fraser and Benzeval, Dr Michaela and Shiels, Professor Paul
• Authors: Maxwell, F., McGlynn, L.M., Muir, H.C., Talwar, D., Benzeval, M., Robertson, T., Roxburgh, C.S., McMillan, D., Horgan, P.G., and Shiels, P.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Clinical Cancer Research
• ISSN: 1078-0432
• ISSN (Online): 1557-3265
• Published Online: 13 July 2011