Polymorphisms in the p53 pathway genes and micronucleus occurrence in Chinese vinyl chloride-exposed workers.
OBJECTIVE
To investigate the association between polymorphisms in the p53 pathway genes and chromosomal damage in vinyl chloride (VC)-exposed workers.


METHODS
Cytokinesis block micronucleus test was performed in 310 VC-exposed workers and 149 non-exposed workers to determine chromosomal damage. The polymerase chain reaction and restriction fragment length polymorphism technique were used to detect six SNPs in the p53 pathway genes involved in the cell cycle.


RESULTS
There was a highly significant dose-response relationship between VC exposure and chromosomal damage. Individuals carrying the variant genotypes were at higher risk for chromosomal damage compared with their wild type genotype: p53rs1042522, MDM2 Del1518rs3730485, MDM2rs2279744 and GADD45Ars532446. On the other hand, individuals possessing the variant genotype of CDKN2A rs3088440 had significantly decreased risk compared with the corresponding wild-type.


CONCLUSIONS
Genetic polymorphisms in P53 pathway genes may have an impact on VC-induced chromosomal damage.
Department of Occupational Health and Toxicology, School of Public Health, Fudan University, Shanghai, China.
Yong
Y
Li
Nan-Nan
NN
Feng
Guang-Hui
GH
Zhang
Qi
Q
Wang
Yan-Hui
YH
Hao
Ya-Nanzhang
Changxu
C
Long
Yongliang
Y
Li
Paul W
PW
Brandt-Rauf
Zhao-Lin
ZL
Xia
D000328:Adult; D002453:Cell Cycle / Q000235:genetics; D002681:China; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects* / Q000032:analysis; D012150:Polymorphism, Restriction Fragment Length / Q000187:drug effects; D020641:Polymorphism, Single Nucleotide / Q000187:drug effects; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D014752:Vinyl Chloride / Q000633:toxicity*; D055815:Young Adult; D000097642:GADD45 Proteins
D019941:Cyclin-Dependent Kinase Inhibitor p16; D047908:Intracellular Signaling Peptides and Proteins; D051736:Proto-Oncogene Proteins c-mdm2; D016159:Tumor Suppressor Protein p53; D014752:Vinyl Chloride; D000097642:GADD45 Proteins