Loss of Y Chromosome in Peripheral Blood of Colorectal and Prostate Cancer Patients

Abstract

BackgroundAlthough age-related loss of chromosome Y (LOY) in normal hematopoietic cells is a well-known phenomenon, the phenotypic consequences of LOY have been elusive. However, LOY has been found in association with smoking, shorter survival and higher risk of cancer. It was suggested that LOY in blood cells could become a predictive biomarker of male carcinogenesis.Aims, Methods & FindingsTo investigate the association of LOY in blood cells with the risk for development of colorectal (CC) and prostate cancers (PC), we have analyzed DNA samples from peripheral blood of 101 CC male patients (mean age 60.5±11.9 yrs), 70 PC patients (mean age 68.8±8.0 yrs) and 93 healthy control males (mean age 65.8±16.6 yrs). The methodology included co-amplification of homologous sequences on chromosome Y and other chromosomes using multiplex quantitative fluorescent (QF) PCR followed by automatic detection and analysis on ABI 3500 Genetic Analyzer. The mean Y/X ratio was significantly lower in the whole group of cancer patients (0.907±0.12; p = 1.17x10-9) in comparison to the controls (1.015±0.15), as well as in CC (0.884±0.15; p = 3.76x10-9) and PC patients (0.941±0.06; p = 0.00012), when analyzed separately. Multivariate logistic regression analysis adjusting for LOY and age showed that LOY is a more significant predictor of cancer presence than age, and that age probably does not contribute to the increased number of subjects with detectable LOY in cancer patients cohort.ConclusionIn conclusion, our results support the recent findings of association of LOY in blood cells with carcinogenesis in males.

Human Y-chromosome variation in the genome-sequencing era

“…LOY is the most common known acquired human mutation in surveyed populations 96 , and its frequency increases with age ( Figure 3A), and is associated with smoking 97 . It has also been associated with decreased survival time from all causes ( Figure 3B), including cancer ( Figure 3C) 96 , and with increased risk of Alzheimer disease ( Figure 3D) 98 ; these associations have been replicated in some but not all studies [99][100][101][102] . The SNP rs2887399 near TCL1A on chromosome 14 is associated with LOY risk (OR = 1.55, 95% CI = 1.36-1.78; P = 1.37 x 10 -10 ) 101 and more recently 18 additional associated genomic regions have been identified 102,103 .…”

Loss of Y Chromosome in Blood Is Associated With Major Cardiovascular Events During Follow-Up in Men After Carotid Endarterectomy

“…2,3 This relationship was speculated to be because of smoking and a disrupted tumor immunosurveillance. …”

Copy‐number analysis of Y‐linked loci in young men with non‐obstructive azoospermia: Implications for the rarity of early onset mosaic loss of chromosome Y

“…The present study aimed to clarify the frequency of cryptic mLOY in young men with spermatogenic failure. To this end, we screened 198 samples using a semi‐quantitative multiplex PCR method, whose sensitivity has been confirmed in previous studies …”

“…Genomic DNA samples were obtained from peripheral blood of each patient. We utilized a previously established method with slight modifications . In brief, copy numbers of chromosome Y relative to chromosome X were assessed by comparing the area under the curve of PCR products for AMELY at Yp11.2 to that for AMELX at Xp22.2.…”

“…To this end, we screened 198 samples using a semi-quantitative multiplex PCR method, whose sensitivity has been confirmed in previous studies. [10][11][12] 2 | MATERIAL S AND ME THODS…”