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. 2016 Jan 8;11(1):e0146264.
doi: 10.1371/journal.pone.0146264. eCollection 2016.

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

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Free PMC article

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

Predrag Noveski et al. PLoS One. .
Free PMC article

Abstract

Background: Although 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 & findings: To 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.

Conclusion: In conclusion, our results support the recent findings of association of LOY in blood cells with carcinogenesis in males.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Electrophoregrams of co-amplified homologous sequences.
Electrophoregrams from subjects with a) normal amelogenin Y/X ratio (approximately equal peak areas of X chromosome and Y chromosome sequences) and b) patient with colorectal cancer and significantly increased proportion of cells with LOY (amelogenin Y/X ratio of 0.28).
Fig 2
Fig 2. Scatter plot of amelogenin Y/X ratio obtained from different proportions of 45,X0 and 46,XY DNA samples.
Dots represent averaged amelogenin Y/X ratio values corresponding to 0%, 2.5%, 5%, 10%, 15%, 20%, 30%, 50%, 70% and 90% of the 45,X0 in the mixed DNA samples. Regression line was estimated using percentage of 45,X0 sample as independent and amelogenin Y/X ratio as dependent variable. Slope (s) and standard deviation (σ) of the regression line were used to calculate the limit of detection using the formula LOD = 3.3σ/s [28].
Fig 3
Fig 3. Histograms of distribution of Y/X ratios in colorectal and prostate cancer patients and controls.
Mean values and standard deviations are also shown.

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This study was supported by project 13-3595/1 from Ministry of Education and Science, Republic of Macedonia (to DPK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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