Abstract 4654: Telomere length as a biomarker of cancer risk: Review and meta-analysis
Authors: Wentzensen Ingrid M. , Mirabello Lisa , Pfeiffer Ruth M. , Savage Sharon A. 
Published: June 2012

Telomere length (TL) in surrogate tissues (e.g., blood or buccal cell DNA) has emerged as a potential biomarker of cancer risk. Telomeric repeats at chromosome ends shorten with each cell division and are essential for chromosomal stability. TL is regulated by a complex network of proteins and may also be affected by environmental exposures which create oxidative stress. The recent, rapid growth of the telomere biology field, and improvements in TL measurement have resulted in a large number of association studies between TL and risk of cancer. Short telomeres are reported to be associated with cancer risk in several case-control studies, but findings are inconsistent in prospective studies. The interpretation of these studies is challenging because of substantial heterogeneity in study design, methods, differences in TL measurements, and often small sample sizes.

We systematically reviewed published studies on the association between TL in surrogate tissues and cancer risk, and conducted formal meta-analyses of reports with comparable design and analysis published before August 30th, 2010. Twenty-seven reports have been published on the association between TL and risk of 13 cancer types and overall incident cancer. The majority (16) included retrospective case-control designs, the others were prospective studies. Sample sizes ranged from 32 cases (renal cancer) to 2,243 colorectal cancer cases. Studies on and overall incident cancer, bladder, esophageal, gastric, head and neck, ovarian, renal found that shorter telomeres significantly increased risk of these cancers. Findings from studies on non-Hodgkin lymphoma, breast, lung and colorectal cancer were inconsistent. Single studies on endometrial, prostate, and skin cancers found no association of cancer risks with TL.

In a random effects meta-analysis, short TL was significantly associated with increased risk of all cancers combined (pooled odds ratio for shortest TL quartile compared to the longest: 1.96, 95% confidence intervals 1.37 – 2.81). Sensitivity analyses showed similar trends, except for the analysis restricted to breast cancers which showed no significant association with TL. Notably, two reports on chromosome-specific TL and risk of esophageal and breast cancers show a strong association. It is biologically conceivable that analyzing TL over all chromosomes combined might attenuate effects.

Our analyses suggest an association between smoking and inflammation-related cancer types and short telomeres, with weaker findings for hormonally influenced malignancies.

In summary, our meta-analysis shows that individuals with shorter-than-average telomeres have increased risks of specific, but not all types of cancer. This study shows that TL is associated with overall cancer risk, but additional prospective studies with consistent methodology are needed on specific cancers to understand the association between TL in surrogate tissues and cancer etiology.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4654. doi:10.1158/1538-7445.AM2011-4654