Association of genetic polymorphisms in GADD45A, MDM2, and p14 ARF with the risk of chronic benzene poisoning in a Chinese occupational population.

Abstract

Benzene reactive metabolites can lead to DNA damage and trigger the p53-dependent defense responses to maintain genomic stability. We hypothesized that the p53-dependent genes may play a role in the development of chronic benzene poisoning (CBP). In a case-control study of 303 patients with benzene poisoning and 295 workers occupationally exposed to benzene in south China, we investigated associations between the risk of CBP and polymorphisms in three p53-dependent genes. Potential interactions of these polymorphisms with lifestyle factors were also explored. We found p14(ARF) rs3731245 polymorphism was associated with risk of CBP (P=0.014). Compared with those carrying the GG genotype, individuals carrying p14(ARF) rs3731245 GA+AA genotypes had a reduced risk of CBP ([adjusted odds ratio (OR(adj))=0.57, 95%CI=0.36-0.89]. Further analysis showed p14(ARF) TGA/TAG diplotype was associated with an increased risk of CBP (P=0.0006), whereas p14(ARF) TGG/TAA diplotype was associated with a decreased risk of CBP (P=0.0000001). In addition, we found individuals carrying both MDM2 Del1518 WW genotype and p14(ARF) rs3731245 GA+AA genotypes had a lower risk of CBP (OR(adj)=0.25; 95%CI=0.10-0.62; P=0.003). Although these results require confirmation and extension, our findings suggest that genetic polymorphisms in p14(ARF) may have an impact on the risk of CBP in the study population.

• Authors: Pin Sun, Zhongbin Zhang, Junxiang Wan, Naiqing Zhao, Xipeng Jin, Zhaolin Xia
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 240 Issue 1 Pg. 66-72 (Oct 01 2009) ISSN: 1096-0333 [Electronic] United States
• PMID: 19596022 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Cycle Proteins
• GADD45A protein, human
• Nuclear Proteins
• Tumor Suppressor Protein p14ARF
• MDM2 protein, human
• Proto-Oncogene Proteins c-mdm2
• Benzene

Topics

• Adolescent
• Adult
• Aged
• Asian People (genetics)
• Benzene (poisoning)
• Case-Control Studies
• Cell Cycle Proteins (genetics)
• Chronic Disease
• Confounding Factors, Epidemiologic
• Female
• Genetic Predisposition to Disease
• Humans
• Male
• Middle Aged
• Nuclear Proteins (genetics)
• Occupational Diseases (chemically induced, epidemiology, genetics)
• Polymorphism, Genetic (genetics)
• Proto-Oncogene Proteins c-mdm2 (genetics)
• Risk Factors
• Tumor Suppressor Protein p14ARF (genetics)
• Young Adult