Highlights • Cr(VI) could cause genetic damage in chromate- exposed populations. • Gene polymorphisms in HRR pathway may modulate the capacity of the repair of DNA damage induced by Cr(VI). • The interaction between rs2295152 polymorphism of XRCC3 and chromate exposure could influence MNF in lymphocytes. • Genetic biomarkers of susceptibility could be potentially helpful in the risk assessment of chromate exposure. Abstract Hexavalent chromium [Cr(VI)] is one of the most common environmental carcinogens, which is associated with DNA damage, genetic instability and increase the risk of cancer development. However, the mechanisms of genetic damage induced by Cr(VI) remains to be thoroughly illustrated. A molecular epidemiological study was conducted on 120 chromate exposed workers and 97 controls. Results indicated that,the rs12432907 of XRCC3 carrying T allele, the rs144848 of BRCA2 with C allele and the rs1805800 of NBS1 with genotype(TT) of individuals were associated with lower genetic damage, while the rs2295152 of XRCC3 carrying T allele, the rs13312986 (CC and CT genotypes) and the rs2697679 of NBS1 with A allele were associated with higher genetic damage in workers exposed to chromate. The interaction of chromate exposure with rs2295152 of XRCC3 had a significant effect on micronuclei frequency (MNF). The gene polymorphisms in homologous recombination repair pathway could modulate chromate-induced genetic damage. [ABSTRACT FROM AUTHOR]