The influence of biological and lifestyle factors on circulating cell-free DNA in blood plasma

Abstract

Research and clinical use of circulating cell-free DNA (cirDNA) is expanding rapidly; however, there remain large gaps in our understanding of the influence of lifestyle and biological factors on the amount of cirDNA present in blood. Here, we review 66 individual studies of cirDNA levels and lifestyle and biological factors, including exercise (acute and chronic), alcohol consumption, occupational hazard exposure, smoking, body mass index, menstruation, hypertension, circadian rhythm, stress, biological sex and age. Despite technical and methodological inconsistences across studies, we identify acute exercise as a significant influence on cirDNA levels. Given the large increase in cirDNA induced by acute exercise, we recommend that controlling for physical activity prior to blood collection is routinely incorporated into study design when total cirDNA levels are of interest. We also highlight appropriate selection and complete reporting of laboratory protocols as important for improving the reproducibility cirDNA studies and ability to critically evaluate the results.

Clinical Application of Noninvasive Prenatal Testing for Sex Chromosome Aneuploidies in Central China

“…The maternal peripheral blood chromosomes of case 10 were proven to have triple X and the maternal karyotype of case 11 was mos 46,XXX,rob(13;14)(q10;q10)[31]/45,XX,rob(13;14)(q10;q10)[19], which led to discordant results ( Table 5 ). Maternal SCA (full or mosaic) is a common and important cause of discordant SCA ( 1 , 27 ) because the majority of plasma cfDNA of pregnant women are derived primarily from cellular apoptosis of the hematopoietic system ( 28 ). Thus, determining the maternal karyotype would increase the accuracy of NIPT results for SCA ( 1 , 29 ).…”

Transcending Blood—Opportunities for Alternate Liquid Biopsies in Oncology

“…cirDNA has been of interest as an analyte in liquid biopsies since 1977, when it was first found to contain ctDNA [ 9 ]. In healthy individuals, cirDNA is present at low levels (10–15 ng/mL blood), though it does increase during tissue stress instigated by exercise, inflammation, or injury [ 10 ]. In cancer patients it can be up to 10-fold higher, especially with metastatic disease, partially due to ctDNA contribution [ 9 ].…”

New Perspectives on the Importance of Cell-Free DNA Biology

“…An evaluation of 25 studies that reported on the relationship between cfDNA and biological sex revealed a greater likelihood of increased cfDNA levels in males vs. females. However, these differences are considered to be minor and may reflect lifestyle differences between males and females, and as such requires further investigation [ 59 ]. Other variables such as haematocrit or cannula placement pain [ 60 ], height [ 61 , 62 ], and the menstrual cycle [ 63 , 64 ] were not found to affect total cfDNA levels.…”

“…To-date, only two studies have investigated the effects of alcohol intake on total cfDNA levels, but no correlation was found [ 70 , 71 ]. However, more research is needed, as these studies had incomplete methodological reporting, used a non-specialized method for cfDNA isolation, failed to specify alcohol intake for subjects in the ‘moderate-severe’ category [ 71 ], have not in their cohort categorization accounted for possible differences between social drinkers and non-drinkers [ 70 ], and were performed in the context of a study on cancer [ 59 ].…”

“…Despite the DNA-damaging effects of cigarette smoking, surprisingly few studies have assessed the correlation between smoking and cfDNA levels. Of the ten studies that have been conducted so far, highly conflicting results were obtained, together showing virtually no correlation between smoking and cfDNA levels [ 59 ]. It is possible that a correlation may be found in clinical studies that have enrolled appropriately powered, equally balanced, and sex- and age-matched subjects into their cohorts, for example.…”