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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Carcinogenesis / genetics*
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Case-Control Studies
  • Chromosome Deletion*
  • Chromosomes, Human, Y*
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / pathology
  • Logistic Models
  • Male
  • Middle Aged
  • Multiplex Polymerase Chain Reaction
  • Neoplasm Staging
  • Prognosis
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology

Substances

  • Biomarkers, Tumor

Grant support

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.