Assessing the Relationship between Leukocyte Telomere Length and Cancer Risk/Mortality in UK Biobank and TCGA Datasets With the Genetic Risk Score and Mendelian Randomization Approaches
Background: Telomere length is an important indicator of tumor progression and survival for cancer patients. Previous work investigated the associations between genetically predicted telomere length and cancers; however, the types of cancers investigated in those studies were relatively limited or the telomere length-associated genetic variants employed often came from genome-wide association studies (GWASs) with small sample sizes.
Methods: We constructed the genetic risk score (GRS) for leukocyte telomere length based on 17 associated genetic variants available from the largest telomere length GWAS up to 78,592 individuals. Then, a comprehensive analysis was undertaken to evaluate the association between the constructed GRS and the risk or mortality of a wide range of cancers [i.e., 37 cancers in the UK Biobank and 33 cancers in The Cancer Genome Atlas (TCGA)]. We further applied the two-sample Mendelian randomization (MR) to estimate the causal effect of leukocyte telomere length on UK Biobank cancers via summary statistics.
Results: In the UK Biobank dataset, we found that the GRS of leukocyte telomere length was associated with a decreased risk of nine types of cancer (i.e., significant association with multiple myeloma, chronic lymphocytic leukemia, kidney/renal cell cancer, bladder cancer, malignant melanoma, basal cell carcinoma, and prostate cancer and suggestive association with sarcoma/fibrosarcoma and Hodgkin’s lymphoma/Hodgkin’s disease). In addition, we found that the GRS was suggestively associated with an increased risk of leukemia. In the TCGA dataset, we observed suggestive evidence that the GRS was associated with a high death hazard of rectum adenocarcinoma (READ), sarcoma (SARC), and skin cutaneous melanoma (SKCM), while the GRS was associated with a low death hazard of kidney renal papillary cell carcinoma (KIRP). The results of MR further supported the association for leukocyte telomere length on the risk of malignant melanoma, Hodgkin’s lymphoma/Hodgkin’s disease, chronic lymphocytic leukemia and multiple myeloma.
Conclusion: Our study reveals that telomere played diverse roles in different types of cancers. However, further validations in large-scale prospective studies and deeper investigations of the biologic mechanisms are warranted.
European Journal of Clinical Oncology Cancer poses a major challenge to development; it undermines socio-economic advances throughout the world. It is estimated that the number of patients with cancer would increase from 12.7 million in the year 2008 to 22.2 million by 2030. It is universally agreed that the condition is reaching epidemic proportions. At this time, the European Journal of Clinical Oncology is conveniently placed in the scholarly communication milieu to help counter the menace of cancer by aiding the development of novel treatment strategies, by providing novel insights into the mechanisms underlying this complex disease.
European Journal of Clinical Oncology publishes peer-reviewed original research articles, review articles, short communications, expert opinions, commentaries and letters/editorials based on open access policy. Author(s) are invited to submit their manuscripts as an e-mail attachment for fast and efficient processing. Aims & scope of the journal, key words, indexing as well as bibliographic information can be accessed at https://www.iomcworld.org/european-clinical-oncology.html
European Journal of Clinical Oncology
Mail ID: email@example.com
WhatsApp no: + 1-504-608-2390