ASPO Abstracts
Differences in leukocyte telomere length, measured using dried blood spot specimens, and survival after colorectal cancer diagnosis
Category: Inflammation & Cancer, Molecular Epidemiology & Environment
Conference Year: 2018
Abstract Body:
Short telomeres have been associated with increased risk of cancers, including colorectal cancer (CRC). However, their role in survival after CRC diagnosis is not clear. We evaluated the association between circulating leukocyte telomere length (LTL) and survival, both overall and CRC-specific, within a subset (n=432) of the Seattle Colon Cancer Family Registry (SCCFR), a prospective cohort of persons diagnosed with CRC between 1997 and 2002. All cases completed a risk-factor questionnaire, including information on demographic and lifestyle factors, and provided blood samples that were stored as dried blood spots. Vital status and cause of death was determined through linkage to a regional cancer registry and National Death Index. Tumor markers (BRAF and KRAS- mutation status) were evaluated on a subset (78%). Telomere length (T) relative to a single copy gene (S) was measured in DNA extracted from circulating leukocytes in stored dried blood spots using quantitative polymerase chain reaction. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression after adjusting for age at diagnosis, sex, BMI, smoking, and NSAID use. After a median of 4.88 years of follow-up since diagnosis, 277 deaths were observed, 200 from CRC. LTL in the shortest tertile (standardized T/S ratio <0.18) was associated with poorer overall survival, however, it did not reach statistical significance [HR(95%CI) =1.12(0.86-1.47)]. There was a suggestion towards difference in association for overall survival by KRAS-mutation status such that poorer survival was observed among KRAS-mutant tumors but not among KRAS wild-type tumors [HR(95%CI) =1.42(0.80-2.50) and 1.00(0.63-1.58), respectively], but this was not statistically significant (p-interaction=0.22). Results for CRC-specific survival were similar. Our results suggest that persons with short LTL, measured using dried blood spots, may experience poorer survival (both overall and CRC- specific) after CRC diagnosis. This was particularly notable for KRAS-mutated tumors, although the association was not statistically significant and sample size was limited. Future larger studies are necessary to further establish the potential relationship between LTL and survival after diagnosis of CRC.
Keywords: Telomere length Colorectal Cancer Survival