# Leukocyte Telomere Length Variants Are Independently Associated with Survival of Patients with Colorectal Cancer

## TL;DR

This study finds that leukocyte telomere length and specific genetic variants are linked to survival outcomes in colorectal cancer patients.

## Contribution

The study identifies specific SNPs in telomere maintenance genes independently associated with CRC survival.

## Key findings

- Leukocyte telomere length is significantly associated with overall and disease-free survival in CRC patients.
- SNPs in TERC and OBFC1 genes are independently linked to survival outcomes in CRC patients.
- Females have significantly longer leukocyte telomere length compared to males.

## Abstract

Telomere length is a well-known determinant of cell health and metabolic status. In general, normal cells have longer telomeres than cancer cells. Importantly, it has been shown that peripheral blood leukocyte telomere length (LTL) can be representative of the overall telomere length of an individual and has shown association with multiple age-related conditions, including cancers. With this rationale, we set out to investigate whether there is any relationship between telomere length and survival of patients with CRC. Our results show that there is a significant relationship between survival and LTL. We also show that alleles of the telomere length maintenance genes TERC and OBFC1 are associated with survival from CRC.

Background and aims: Aberrations in telomere length can have important implications in cancer. Using a cohort of 1007 patients, we investigated whether leukocyte telomere length (LTL) in patients with colorectal cancer (CRC) is associated with survival. We also investigated whether some telomere maintenance genes are associated with survival in these patients. Methods: The Biobank for Gastrointestinal Health Research (BGHR), an ongoing project involving collection of biospecimens at the Mayo Clinic, was utilized to obtain data from patients diagnosed with stage II or III CRC. Blood samples were collected prior to chemotherapy/radiation and DNA was extracted for measuring median LTL. The main outcome measures were overall survival (OS) and disease-free survival (DFS) by disease stage. Results: A significant inverse relationship was observed with patient age and LTL (spearman correlation coefficient (r) = −0.48, 95%; p = 1.13 × 10−58). Females had significantly longer LTL than males (p = 3.97 × 10−5). The rs1317082 SNP in the TERC gene was significantly associated with both OS and DFS in combined stage II and stage III patients (p = 0.017 and p = 0.023, respectively). A statistically significant association of the OBFC1 SNP (rs9419958) was observed for OS for the combined stage II and stage III patients (p = 0.016). Importantly, LTL was significantly associated with both OS and DFS (p = 0.008 and 0.044 respectively) in combined stage II and stage III patients. Conclusions: Our results show that LTL is predictive of OS and DFS for stage II and III CRC patients, particularly over a longer follow-up, extending beyond five years after a diagnosis of CRC, and certain SNPs in genes involved in telomere maintenance are significantly associated with patient outcomes, independent of telomere length.