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.
Highlights
Loss of Y chromosome (LOY) is a well-known phenomenon that is associated with aging and observed with varying frequencies in bone marrow cells [1,2] or in peripheral blood cells [3,4] from healthy older males
Our results support the recent findings of association of LOY in blood cells with carcinogenesis in males
Normal 46,XY DNA sample and nine mixed DNA samples with different proportions of 46, XY and 45,X0 DNA samples were amplified in triplicate and corresponding amelogenin Y/X ratio was obtained for each proportion
Summary
Loss of Y chromosome (LOY) is a well-known phenomenon that is associated with aging and observed with varying frequencies in bone marrow cells [1,2] or in peripheral blood cells [3,4] from healthy older males. Other studies have found the association only in patients who showed LOY in more than 75% [10] or 100% of the affected cells [11]. Recent study investigating LOY in two separate peripheral blood cell fractions found significantly higher frequency of LOY in CD34+ cells in patients with myelodysplastic syndromes compared with elderly men without hematologic diseases [12]. A study showing no association between LOY and hematological cancers has been published [13]. It was suggested that LOY in blood cells could become a predictive biomarker of male carcinogenesis
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