Polymorphism of XRCC1 Gene Exon 6 (Arg194Trp) in Relation to Micronucleus Frequencies in Hospital Radiation Workers

The genetic polymorphism of deoxyribonucleic acid (DNA) repair genes plays
important roles in regulating individual sensitivity to ionizing radiation, maintaining
DNA integrity, and preventing cancer and DNA damage. X-ray repair crosscomplementary
group 1 (XRCC1) as one of the members of base excision repair
(BER) is involved in the repairement of oxidized bases and single-strand breaks
DNA after exposure by reactive oxygen species (ROS), including ionizing radiation.
This study aimed to examine the correlation between XRCC1 exon 6 gene
polymorphism and micronucleus (MN) frequency in radiation workers and their
relation to age, gender, smoking status and years of exposure. This study involved
81 hospital radiation workers and 20 controls from several hospitals in Indonesia.
Genotyping of XRCC1 exon 6 gene polymorphism and MN assay were performed
using polymerase chain reaction-restriction fragment length polymorphism
(PCR-RFLP) and cytokinesis-block micronucleus assay (CBMN assay),
respectively. The results indicated that MN frequency was significantly higher in
the exposed workers than in the controls (15.38 ± 7.72 versus 9 ± 5.49; p = 0.001).
Radiation workers with heterozygous alleles for XRCC1 polymorphisms showed a
significantly higher MN frequency than controls with the same genotypes
(17.5 ± 8.36 versus 7.44 ± 5.05; p = 0.002). The confounding factors, like gender
and age, were significantly associated with increased MN frequency both in
radiation workers and controls. Smoking status was significantly associated with
MN frequency in the controls only, while years of exposure did not affect
MN frequency either in radiation workers or controls. These results suggest
that the genetic polymorphism of XRCC1 gene exon 6 with a mutant
heterozygous/cytosine-thymine (CT) variant demonstrated an association with the
extent of DNA damage in the hospital radiation workers in this study. In the
subsequent studies, it will be necessary to examine the DNA repair
genes polymorphism in populations with controlled non-genetic factors, such as
lifestyle, environment, and exercise, that affect the MN frequency as a biomarker of
DNA damage