The European Prospective Investigation into Cancer and nutrition (EPIC) is a long-term, multi-centric prospective study in
Europe investigating the relationships between cancer and nutrition. This study has served as a basis for a number of
Genome-Wide Association Studies (GWAS) and other types of genetic analyses. Over a period of 5 years, 52,256 EPIC DNA
samples have been extracted using an automated DNA extraction platform. Here we have evaluated the pre-analytical
factors affecting DNA yield, including anthropometric, epidemiological and technical factors such as center of subject
recruitment, age, gender, body-mass index, disease case or control status, tobacco consumption, number of aliquots of
buffy coat used for DNA extraction, extraction machine or procedure, DNA quantification method, degree of haemolysis and
variations in the timing of sample processing. We show that the largest significant variations in DNA yield were observed
with degree of haemolysis and with center of subject recruitment. Age, gender, body-mass index, cancer case or control
status and tobacco consumption also significantly impacted DNA yield. Feedback from laboratories which have analyzed
DNA with different SNP genotyping technologies demonstrate that the vast majority of samples (approximately 88%)
performed adequately in different types of assays. To our knowledge this study is the largest to date to evaluate the sources
of pre-analytical variations in DNA extracted from peripheral leucocytes. The results provide a strong evidence-based
rationale for standardized recommendations on blood collection and processing protocols for large-scale genetic studies.