Biological monitoring of workers exposed to carcinogens using the buccal micronucleus approach: A systematic review and meta-analysis.

A biomarker-based approach using micronucleus (MN) (extranuclear DNA-containing bodies) frequencies in buccal cells has been proposed to monitor workers exposed to aero-digestive carcinogens for early detection of occupational cancer. To assess this non-invasive MN approach, we sought to understand: (A) What is the extent of MN frequency increase in occupationally exposed over non-exposed populations across studies published in the scientific literature for buccal cells; and (B) Which types of occupational exposures give relevant summary MN ratios across studies published in the scientific literature. A systematic literature review was performed, and the MN frequency ratios for buccal cells were calculated for each occupational study. Meta-analytic techniques were applied using the confidence interval or a standard error on the log-transformed ratio. Exposure categories were developed based on similar occupational exposures or jobs. A summary ratio and proportion of variance explained (the I <sup>2</sup> index) were derived assuming a Gaussian random effect model for each exposure category. The meta-analysis of the published literature (n = 96 studies) showed large random variability between studies within each category (I <sup>2</sup> > 90%), except where exposures were to a single carcinogenic substance (e.g. formaldehyde, silica) or similar jobs were performed (e.g. antineoplastic dispensing, gasoline attendants). The greatest summary frequency ratios were for silica (FR 9.02 95%CI 6.83-11.93), formaldehyde (FR 4.81 95%CI 2.19-10.60), and for hairdressers as an exposure category (FR 7.06 95%CI 3.96-12.57). The unexplained between-study variability can be related to exposures to mixtures of carcinogens with unknown mechanisms. If the latter had been measured, the between-study variability may have been explained. We conclude that better exposure assessments are needed to understand the relationship between occupational exposures and MN frequency responses in buccal cells. Nevertheless, our analysis indicates that the buccal cell MN assay is a promising tool for surveying workers exposed to genotoxic agents