7 research outputs found
Polymorphisms associated with the risk of lung cancer in a healthy Mexican Mestizo population: Application of the additive model for cancer
Lung cancer is the leading cause of cancer mortality in Mexico and worldwide. In the past decade, there has been an increase in the number of lung cancer cases in young people, which suggests an important role for genetic background in the etiology of this disease. In this study, we genetically characterized 16 polymorphisms in 12 low penetrance genes (AhR, CYP1A1, CYP2E1, EPHX1, GSTM1, GSTT1, GSTPI, XRCC1, ERCC2, MGMT, CCND1 and TP53) in 382 healthy Mexican Mestizos as the first step in elucidating the genetic structure of this population and identifying high risk individuals. All of the genotypes analyzed were in Hardy-Weinberg equilibrium, but different degrees of linkage were observed for polymorphisms in the CYP1A1 and EPHX1 genes. The genetic variability of this population was distributed in six clusters that were defined based on their genetic characteristics. The use of a polygenic model to assess the additive effect of low penetrance risk alleles identified combinations of risk genotypes that could be useful in predicting a predisposition to lung cancer. Estimation of the level of genetic susceptibility showed that the individual calculated risk value (iCRV) ranged from 1 to 16, with a higher iCRV indicating a greater genetic susceptibility to lung cancer
Cytogenetic biomarkers, urinary metabolites and metabolic gene polymorphisms in workers exposed to styrene
The present study comprised a biomonitoring study in 95
workers occupationally exposed to styrene and 98
unexposed controls, employing an integrated approach
involving biomarkers of exposure, effect, and susceptibility.
Airborne styrene was evaluated at workplace, and urinary
styrene metabolites, mandelic acid (MA), phenylglyoxylic
acid (PGA), vinylphenols (VPTs) and Phenylhydroxyethylmercapturic
acids (PHEMAs), were measured as
biomarkers of internal dose. Cytogenetic alterations were
evaluated by analysing the frequency of chromosomal
aberrations (CAs) and micronucleated binucleated cells
(MNBN) in peripheral blood lymphocytes. The micronucleus
assay was coupled with centromeric fluorescence
in situ hybridization to distinguish micronuclei (MN) arising
from chromosomal breakage (C â MN) from those
harboring whole chromosomes (C + MN). The possible
influence of genetic polymorphisms of xenobiotic-metabolizing
enzymes involved in styrene biotransformation
(EPHX1, GSTT1, GSTM1, GSTP1) and NAT2 on the
cytogenetic endpoints was investigated. The exposed
workers showed a significantly higher frequency of MNBN
(13.8 ± 0.5% versus 9.2± 0.4%; P <0.001) compared to
control subjects. The effect appeared to concern both
C â and C+ MN. A positive correlation was seen between
the frequency of C+ MN and urinary level of MA+ PGA
(P < 0.05) and VPTs (P < 0.001). Chromosome-type CAs
positively correlated with airborne styrene level and VPTs
(P < 0.05), whereas chromatid-type CAs correlated with
PHEMAs (P <0.05). Workers bearing GSTM1 null genotype
showed lowered levels of PHEMAs (P <0.001). The GSTT1
null genotype was associated with increased MNBN frequencies in the exposed workers (P < 0.05) and the fast
activity EPHX genotype with a moderate decrease in both
MNBN and CAs in the controls. Our results suggest that
occupational exposure to styrene has genotoxic effects
that are potentiated by the GSTT1 gene deletion.
These observations may have relevance considering
the risk of lymphatic and haematopoietic malignancies
tentatively associated with styrene exposure