Short leukocyte telomere length predicts poor prognosis and indicates altered immune functions in colorectal cancer patients

Chen, Y.; Qu, Fengli; He, Xianli; Bao, Guoqiang; Liu, X.; Wan, Shaogui; Xing, Jinliang

doi:10.1093/annonc/mdu016

Cited by 45 publications

(62 citation statements)

References 22 publications

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“…Longer cancer telomere length or higher cancer to non-cancer tissue telomere length ratios have been associated with poorer prognosis in three reports [11, 12, 14], but another study has found opposite results [9]. Variation in normal tissue telomere length (for PBLs) has further been suggested as a marker of CRC prognosis [31]. In our cohort of patients with stage II/III CRC we found no evidence of normal or cancer RTL associated with disease-free survival or overall survival.…”

Section: Discussionmentioning

confidence: 99%

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Relative telomere lengths in tumor and normal mucosa are related to disease progression and chromosome instability profiles in colorectal cancer

Suraweera

Mouradov

et al. 2016

Oncotarget

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Telomeric dysfunction is linked to colorectal cancer (CRC) initiation. However, the relationship of normal tissue and tumor telomere lengths with CRC progression, molecular features and prognosis is unclear. Here, we measured relative telomere length (RTL) by real-time quantitative PCR in 90 adenomas (aRTL), 419 stage I-IV CRCs (cRTL) and adjacent normal mucosa (nRTL). Age-adjusted RTL was analyzed against germline variants in telomere biology genes, chromosome instability (CIN), microsatellite instability (MSI), CpG island methylator phenotype (CIMP), TP53, KRAS, BRAF mutations and clinical outcomes. In 509 adenoma or CRC patients, nRTL decreased with advancing age. Female gender, proximal location and the TERT rs2736100 G allele were independently associated with longer age-adjusted nRTL. Adenomas and carcinomas exhibited telomere shortening in 79% and 67% and lengthening in 7% and 15% of cases. Age-adjusted nRTL and cRTL were independently associated with tumor stage, decreasing from adenoma to stage III and leveling out or increasing from stage III to IV, respectively. Cancer MSI, CIMP, TP53, KRAS and BRAF status were not related to nRTL or cRTL. Near-tetraploid CRCs exhibited significantly longer cRTLs than CIN- and aneuploidy CRCs, while cRTL was significantly shorter in CRCs with larger numbers of chromosome breaks. Age-adjusted nRTL, cRTL or cRTL:nRTL ratios were not associated with disease-free or overall survival in stage II/III CRC. Taken together, our data show that both normal mucosa and tumor RTL are independently associated with CRC progression, and highlight divergent associations of CRC telomere length with tumor CIN profiles.

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Section: Discussionmentioning

confidence: 99%

“…Telomere length of peripheral blood leukocytes (PBL) and variants in TERT and TERC have been associated with CRC susceptibility, with evidence that both shorter and longer telomere lengths may play a role [28–30]. One study has identified PBL telomere length as an independent prognostic marker for CRC [31]. …”

Section: Introductionmentioning

confidence: 99%

Relative telomere lengths in tumor and normal mucosa are related to disease progression and chromosome instability profiles in colorectal cancer

Suraweera

Mouradov

et al. 2016

Oncotarget

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“…After full-text review, one publication was excluded for containing overlapping data [21]. One publication contained three individual cohort studies, and was extracted as three different cohort studies [15]. Thus, 7 individual studies from 5 articles were included [12][13][14][15][16].…”

Section: Study Selection and Characteristicsmentioning

confidence: 99%

Telomere Length as a Prognostic Factor for Overall Survival in Colorectal Cancer Patients

Jia

Wang²

2016

Cell Physiol Biochem

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Background/Aims: The stabilization of telomere length has important roles in the carcinogenesis of colorectal cancer. A systemic review and meta-analysis of published studies was performed to assess the prognostic role of telomere length in colorectal cancer. Methods: Pubmed and Embase were searched for eligible studies on the association between telomere length and overall survival in colorectal cancer patients. The pooled hazard ratio (HR) and corresponding 95% confidence intervals (95%CI) was calculated using fixed-effects or random-effects model according to the magnitude of between-study heterogeneity. Results: Seven individual studies with a total of 956 colorectal cancer patients were included. Long telomere length in cancer tissues was marginally associated with poorer overall survival (Random-effects HR = 1.85, 95% 0.90 to 3.83, P = 0.09). When using studies with adjusted estimates, long telomere length in cancer tissues was independently and significantly associated with poorer overall survival (Fixed-effects HR = 2.70, 95% 1.51 to 4.84, P = 0.001). However, short telomere length in peripheral blood leukocytes was independently and significantly associated with poorer overall survival (Fixed-effects HR = 2.01, 95% 1.46 to 2.77, P < 0.001). Conclusions: There is some evidence for telomere length as a prognostic factor for overall survival in colorectal cancer patients. More studies with large number of participants are needed to further assess the prognostic significance of telomere length in colorectal cancer patients.

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“…5 We have also offered some potential biological explanations for this observed improved survival in patients with melanoma with an excess of naevi via telomeres, and though this is speculative, it has already been shown, in colon cancer, that telomere length may have a favourable effect on mortality. 6 Telomere length is associated with both melanoma susceptibility and an excess of naevi, and other studies are needed to replicate our results and also investigate melanoma prognosis in relation to telomere length.Naevus number is associated with the presence of atypical or dysplastic naevi. It is established that superficial spreading melanomas are more likely to be reported by histopathologists as arising in atypical or dysplastic naevi than are nodular melanomas 7 and that superficial spreading tumours seen to have developed in association with dysplasia demonstrate…”

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confidence: 56%

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confidence: 56%

Authors' reply to: High naevus counts confer a favourable prognosis in patients with melanoma

Ribero

Davies

Glass

et al. 2015

Intl Journal of Cancer

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Dear Editor, We welcome the comments by Autier et al. These correspondents have drawn attention to the reported different outcomes for cancers detected by screening.In our study, 1 we reported evidence for better survival in patients with melanoma with many naevi, suggesting that this might reflect a different biology in this subset of melanomas. Autier et al. have suggested that an alternative explanation might be that the better survival observed in patients with many naevi may in fact result from a selection bias due to these tumours being discovered by screening.The intent of screening is indeed to detect cancers earlier and therefore by definition with a better prognosis. The issue here is whether the patients with higher naevus counts recruited to our studies were more likely to be diagnosed early as a result of screening. There are no formal screening programmes for melanoma in either Spain or the United Kingdom. The UK series were unselected patients with melanoma from a defined geographical area. Very few were identified in follow-up, although this is not quantified. All the Spanish patients included in our study underwent sentinel lymph node biopsy. Sentinel lymph node biopsy is only performed for tumours of Stage IB or higher. There is published data which suggest that melanomas diagnosed in follow-up screening were unlikely to have been offered sentinel node biopsy and are therefore unlikely to have been included in our study. 1 In the Barcelona Melanoma Unit, melanomas diagnosed in patients undergoing screening were reported to be all Stage 0 or IA. 2 When using total body photography and digital dermoscopy, none of the 98 melanomas diagnosed during screening required sentinel lymph node biopsy in a mean follow-up of 98 months. 3,4 We suggest that it is therefore unlikely that the observations reported in our study reflect a screening artefact and more likely to represent a true biological effect.Sentinel node biopsy is a staging tool for patients with thicker primaries, and therefore, the Spanish studies describe participants selected for thicker tumours. The mean thickness of cases included in the model in Table 3 was 2.45 mm. The cases included in the model in Table 4 had a mean Breslow thickness of 3.42 mm. In particular, mean Breslow thickness in the melanoma cases included in the model (Table 3) with >50 naevi was 2.07 mm. The effect of increased numbers of naevi on improved survival remained in the positive sentinel group (Fig. 2). We would argue that this provides evidence to support our hypothesis that the protective effect on survival was not related to selection bias.The multivariate models have been performed with Breslow thickness as both linear and categorical variables. In both models, the protective effects of naevus count on melanoma mortality were maintained. The multivariate models had been performed with Breslow thickness either as a linear or categorical variable. In both models, the protective effects of nevus count on melanoma mortality were maintained. We performed a log like...

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Short leukocyte telomere length predicts poor prognosis and indicates altered immune functions in colorectal cancer patients

Cited by 45 publications

References 22 publications

Relative telomere lengths in tumor and normal mucosa are related to disease progression and chromosome instability profiles in colorectal cancer

Relative telomere lengths in tumor and normal mucosa are related to disease progression and chromosome instability profiles in colorectal cancer

Telomere Length as a Prognostic Factor for Overall Survival in Colorectal Cancer Patients

Authors' reply to: High naevus counts confer a favourable prognosis in patients with melanoma

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