Telomere length and LINE1 methylation is associated with chromosomal aberrations in peripheral blood.

The frequency of chromosomal aberrations in peripheral blood predicts a probable cancer risk. The individual telomere length and methylation of repetitive elements may be susceptibility factors for chromosomal aberrations. A cohort of healthy Norwegian men (N = 364) recruited during 1980-1999 were analyzed for chromosomal aberrations in phytohemagglutinin-stimulated lymphocytes from peripheral blood. Chromosome-type or chromatid-type aberrations were scored. DNA was extracted from slides cytogenetically analyzed and relative average telomere length and methylation of LINE1 repeats were determined by quantitative polymerase chain reaction and bisulfite pyrosequencing, respectively. Information about individuals with malignant tumors (N = 49) diagnosed after chromosomal aberrations testing until end of 2008 was obtained and two matched controls per case were used in a nested case-control analysis. Shorter relative telomere length and higher methylation of LINE1 were associated with higher frequency of total chromosomal aberrations (β = -0.76, P = 0.022; and β = 0.042, P = 0.048, respectively; age-adjusted ordinal regression). The telomere length was stronger associated with chromosome-type (β = -1.00, P = 0.006) than with chromatid-type aberrations (β = -0.49, P = 0.115). The LINE1 methylation was stronger associated with chromatid-type (β = 0.062, P = 0.003) than with chromosome-type aberrations (β = 0.018, P = 0.41). Telomere length [individuals with short telomeres odds ratio (OR) = 0.87, 95% confidence interval (CI) 0.38-2.0], LINE1 (individuals with high methylation OR = 1.04, 95% CI 0.43-2.5) and chromosomal aberrations (individuals with high frequency OR = 1.6, 95% CI 0.63-3.9) at baseline did not predict cancer risk, but the conclusions were hampered by low statistical precision. The results suggest that shorter telomere length and higher LINE1 methylation in peripheral blood lymphocytes are predisposition factors for increased frequency of chromosomal aberrations.