Association between telomere length and the risk of colorectal cancer: a meta-analysis of observational studies

Abstract

BackgroundHuman chromosomes are capped and stabilized by telomeres. Telomere length regulates a ‘cellular mitotic clock’ that defines the number of cell divisions and hence, cellular life span. This study aimed to synthesize the evidence on the association between peripheral blood leucocytes (PBL) telomere length and the risk of colorectal cancer (CRC).MethodsWe searched relevant studies in electronic databases. When two or more observational studies reported the same outcome measures, we performed pooled analysis. All the analyses were performed on PBL using PCR. The odds ratio (OR) and its 95% confidence interval (CI) were used to assess the strength of association.ResultsSeven studies (with 8 datasets) were included in this meta-analysis; 3 prospective studies, 3 retrospective studies and 1 study with a separate prospective and retrospective designs. The pooled analysis of 4 prospective studies (summary OR 1.01, 95% CI: 0.77–1.34, I 2:30%) and 4 retrospective studies (summary OR 1.65, 95% CI: 0.96–2.83, I 2:96%) showed no relationship between PBL telomere length and the CRC risk. A subgroup analysis of 2 prospective studies exclusively on females also showed no association between PBL telomere length and the CRC risk (summary OR, 1.17, 95% CI:0.72–1.91, I 2:57%).ConclusionThe current analysis is insufficient to provide evidence on the relationship between PBL telomere length and the risk of CRC. Findings suggest that there may be a complex relationship between PBL telomere length and the CRC risk or discrepancy between genetics, age of patients and clinical studies. Future well powered, large prospective studies on the relationship between telomere length and the risk of CRC, and the investigations of the biologic mechanisms are recommended.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2997-3) contains supplementary material, which is available to authorized users.

Should we invest in biological age predictors to treat colorectal cancer in older adults?

“…Long telomeres is a risk factor for glioma, lung, ovarian, testicular, kidney, skin, endometrial and neuroblastoma cancers [9]. For CRC, observational studies find no evidence of an association between short or long telomeres and disease development [10]. Using genetically predicted telomere length in a so called Mendelian Randomization analysis, unconfounded associations with CRC where confirmed negative [9].…”

A Rare Variant P507L in TPP1 Interrupts TPP1–TIN2 Interaction, Influences Telomere Length, and Confers Colorectal Cancer Risk in Chinese Population

“…Nevertheless, a study demonstrated an U-shaped association between TL and colorectal cancer initiation (28). On the basis of the combination of 8 datasets, a meta-analysis showed that TL was not contributed to colorectal cancer risk (29). Hence, the relationship between TL and colorectal cancer development needs to further investigate.…”

Telomere length in the colon is related to colorectal adenoma prevalence

“…The relationship between telomere length and colorectal risk has largely been studied by measuring telomere length in peripheral blood leukocytes and there is considerable heterogeneity in results across studies [ 30 ]. Prospective studies of this relationship have consisted of three case-control studies, nested within existing large cohorts, which have measured telomere length in stored blood samples collected at recruitment [ 37 – 39 ].…”

“…Some traditional case-control studies have shown short telomeres are associated with increased risk of colorectal cancer [ 39 , 41 , 42 ]; yet, other case-control studies have shown that both short and long telomeres are related to increased colorectal cancer risk [ 43 , 44 ]. Collectively, these results indicate that the relationship between telomere length and colorectal cancer risk may be complex and suggest that telomere length, at least as measured in peripheral blood leukocytes, is not strongly related to colorectal cancer risk years later [ 30 ]. Telomere dynamics in colonocytes differ from those in other tissues, specifically those of peripheral blood leukocytes [ 47 ].…”

“…Therefore, compared to somatic cells with short telomeres, those with constitutively longer telomeres are at increased risk of acquiring additional genetic alterations that may ultimately lead to malignant transformation and progression [ 21 , 23 – 25 ]. Epidemiologic research into the relationship between telomere length and cancer risk generally has been inconsistent and results imply that the relationship varies by cancer site [ 26 – 30 ]. Many early studies indicated that shorter telomeres were associated with an increased risk for developing bladder, esophageal, gastric, and head and neck cancers [ 27 ].…”