Telomere Length Studies in PLCO
Despite abundance of studies, the TL literature has suffered from methodological limitations and a lack of consistency in association studies with disease. Examples include: measurement errors related to the use of different DNA extraction and handling methods in qPCR TL assay; reverse-causation in case-control studies; and a lack of accurate information on attrition rates during the lifespan due to a lack of studies using serial samples. Here, we propose to use samples extracted for the PLCO GSA project (n~100,000) to better understand the relationship of TL genetic and epidemiological variation with cancer. We propose to use a robust and high throughput standardized qPCR assay at the NCI Center for Genomic Research (CGR) in combination with highly accurate flow FISH assay for a subset with viable crypopreserved samples. Flow FISH measurements will be used to calibrate the qPCR assay, facilitating robust interpretation. This work will generate a unique resource for investigators interested in telomere length studies.
1. Improve the understanding of telomere length genomic through a large-scale telomere length genome-wide association study.
2. Develop and validate an absolute telomere length calibration equation in a subset of participants receiving both qPCR and flow-FISH measurements.
3. Integrating both telomere length and GWAS data to understand the contribution of telomere length genetics in the risk of cancer development.
Shahinaz Gadalla (National Cancer Institute, NIH)
Sharon Savage (National Cancer Institute, NIH)
Hourmuzd Katki (National Cancer Institute, NIH)
Mitchell Machiela (National Cancer Institute, NIH)