Longer Telomeres Are Associated with Cancer Risk in MMR-Proficient Hereditary Non-Polyposis Colorectal Cancer

Seguí, Núria; Guinó, Elisabet; Pineda, Marta; Navarro, Matilde; Bellido, Fernando; Lázaro, Conxi; Blanco, Ignacio; Capellà, Gabriel; Valle, Laura

doi:10.1371/journal.pone.0086063

Cited by 14 publications

(12 citation statements)

References 22 publications

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“…Our principal finding was that cases with colorectal polyps or CRC had longer bowel telomeres, independent of other risk factors. There is a controversy about the effects of telomere length on the risk of many cancers, including CRC ( Quin et al , 2014 ; Seguí et al , 2014 ), but almost all studies have measured telomere length in peripheral blood. Our finding of no correlation between telomere length in the colorectum and blood may help to explain the inconsistent results of previous studies.…”

Section: Discussionmentioning

confidence: 99%

Telomere length and genetics are independent colorectal tumour risk factors in an evaluation of biomarkers in normal bowel

Fernández–Rozadilla

Kartsonaki²,

Woolley

et al. 2018

Br J Cancer

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Background:Colorectal cancer (CRC) screening might be improved by using a measure of prior risk to modulate screening intensity or the faecal immunochemical test threshold. Intermediate molecular biomarkers could aid risk prediction by capturing both known and unknown risk factors.Methods:We sampled normal bowel mucosa from the proximal colon, distal colon and rectum of 317 individuals undergoing colonoscopy. We defined cases as having a personal history of colorectal polyp(s)/cancer, and controls as having no history of colorectal neoplasia. Molecular analyses were performed for: telomere length (TL); global methylation; and the expression of genes in molecular pathways associated with colorectal tumourigenesis. We also calculated a polygenic risk score (PRS) based on CRC susceptibility polymorphisms.Results:Bowel TL was significantly longer in cases than controls, but was not associated with blood TL. PRS was significantly and independently higher in cases. Hypermethylation showed a suggestive association with case:control status. No gene or pathway was differentially expressed between cases and controls. Gene expression often varied considerably between bowel locations.Conclusions:PRS and bowel TL (but not blood TL) may be clinically-useful predictors of CRC risk. Sample collection to assess these biomarkers is feasible in clinical practice, especially where population screening uses flexible sigmoidoscopy or colonoscopy.

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Section: Discussionmentioning

confidence: 99%

Telomere length and genetics are independent colorectal tumour risk factors in an evaluation of biomarkers in normal bowel

Fernández–Rozadilla

Kartsonaki²,

Woolley

et al. 2018

Br J Cancer

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“…In some types of cancers, such as gastric and bladder cancer, shorter RTL in leukocytes was a risk factor of tumorigenesis, [12,13,21] while it was opposite in lung and colorectal cancer. [17,18] …”

Section: Discussionmentioning

confidence: 99%

“…Some findings showed that shorter telomere length not only increases the risk of gastric cancer, [12] but also decreases the survival rate of bladder cancer, [13] while in other epidemiologic investigates, longer telomere length was associated with the increased risk of cancers that were reported. [14–18] To date, little research has investigated the relationship between telomere length and the event of hepatocarcinogenesis (from normal, CHB to HCC) to our knowledge. In this study, the changes of leukocytes telomere length in different cohorts of diseases in a southwest Han Chinese population were investigated to try to understand the relationship of RTL in different stages of hepatocarcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

Association of telomere length in peripheral leukocytes with chronic hepatitis B and hepatocellular carcinoma

Cai

et al. 2016

Medicine

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Background & Objectives: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.Conclusion: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.

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“…After screening titles and abstracts, 20 full texts were retrieved; seven studies (with 8 data sets) [22–28] were selected for inclusion in this meta-analysis. Thirteen studies [29–41] were excluded as they did not meet the inclusion criteria. Reasons for the exclusion were summarized in Additional file 2: Table S1.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2017

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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.

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Longer Telomeres Are Associated with Cancer Risk in MMR-Proficient Hereditary Non-Polyposis Colorectal Cancer

Cited by 14 publications

References 22 publications

Telomere length and genetics are independent colorectal tumour risk factors in an evaluation of biomarkers in normal bowel

Telomere length and genetics are independent colorectal tumour risk factors in an evaluation of biomarkers in normal bowel

Association of telomere length in peripheral leukocytes with chronic hepatitis B and hepatocellular carcinoma

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

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