Validation of micronuclei frequency in peripheral blood lymphocytes as early cancer risk biomarker in a nested case–control study

Abstract

Aim of this work was to assess the predictive value of micronuclei (MN) frequency in peripheral blood lymphocytes (PBL) for the risk of cancer death in disease-free individuals. Blood samples from 1650 subjects selected from the general population of Pisa, Italy, were collected between June 1991 and November 1993. The follow-up until January 2005 recorded a total of 111 deaths (52 for cancer). MN frequency was assessed for 49 cancer cases and 101 matched controls. A significantly higher MN frequency was found in cancer cases (4.7 ± 3.4 MN/1000 BN cells) versus controls (1.5 ± 1.7; p < 0.0001). Donors were stratified in two classes and multivariate logistic regression analysis confirmed that individuals with high MN frequency (>2.5 MN/1000 BN cells) had a significantly increased risk of cancer death (OR = 10.7; 95% CI = 4.6–24.9; p < 0.0001) when compared to individuals with low MN frequency (≤2.5 MN/1000 BN cells). Ageing was associated with a 6% increased risk per year ( p = 0.03). No influence of other potential confounders (gender, occupation, smoking and drinking habits) was observed. Finally, subjects with a higher MN frequency showed a higher MR for CVD (Logrank test, p = 0.001). These findings provide strong evidence that MN frequency assessed in PBL of disease-free subjects is a good predictor of cancer death risk, evaluated by a nested case–control study performed 14 years after the original recruitment.