Sun Pin, Qiu Yulan, Zhang Zhongbin, Wan Junxiang, Wang Tong, Jin Xipeng, Lan Qing, Rothman Nathaniel, Xia Zhao-lin
Department of Occupational Health, School of Public Health, Fudan University, Shanghai, China.
Cancer Epidemiol Biomarkers Prev. 2009 Jun;18(6):1821-8. doi: 10.1158/1055-9965.EPI-09-0140.
DNA damage induced by benzene reactive metabolites is thought of as an important mechanism underlying benzene hematotoxicity and genotoxicity, and genetic variation in cell-cycle control genes may contribute to susceptibility to chronic benzene poisoning (CBP). Using a case-control study that included 307 benzene-poisoned patients and 299 workers occupationally exposed to benzene in south China, we aimed to investigate the association between genetic polymorphisms of p53 and p21 and the odds of CBP. To investigate whether benzene exposure may influence mRNA expression of p53 and p21 in benzene-exposed workers, we also chose 39 CBP workers, 38 occupationally benzene-exposure workers, and 37 nonexposure workers in the same region of China. PCR-restriction fragment length polymorphism technique was applied to detect polymorphisms of p53 (rs17878362, rs1042522, and rs1625895) and p21 (rs1801270 and rs1059234), and real-time PCR was applied to detect the quantity of gene mRNA expression. We found that p21 C98A variant genotypes (CA+AA) or C70T variant genotypes (CT+TT) were associated with decreased odds of CBP [odds ratio (OR), 0.51; 95% confidence interval (95% CI), 0.32-0.83, and OR, 0.53; 95% CI, 0.29-0.95, respectively. Further analysis showed the decreased odds of CBP in the subjects with p21 CC/AT diplotype (OR, 0.51; 95% CI, 0.30-0.85). In addition, p53 mRNA expression of CBP workers or benzene-exposure workers was significantly lower than that of nonexposure workers. Although these results require confirmation and extension, our results show that polymorphisms in p21 may be protective against the risk of CBP in the Chinese occupational population.
苯反应性代谢产物诱导的DNA损伤被认为是苯血液毒性和遗传毒性的重要潜在机制，细胞周期调控基因的遗传变异可能导致对慢性苯中毒（CBP）的易感性。我们采用病例对照研究，纳入了中国南方307名苯中毒患者和299名职业性接触苯的工人，旨在研究p53和p21基因多态性与CBP发病几率之间的关联。为了研究苯暴露是否会影响苯接触工人中p53和p21的mRNA表达，我们还在中国同一地区选择了39名CBP工人、38名职业性苯接触工人和37名非接触工人。应用聚合酶链反应-限制性片段长度多态性技术检测p53（rs17878362、rs1042522和rs1625895）和p21（rs1801270和rs1059234）的多态性，并应用实时聚合酶链反应检测基因mRNA表达量。我们发现，p21 C98A变异基因型（CA+AA）或C70T变异基因型（CT+TT）与CBP发病几率降低相关[比值比（OR）分别为0.51；95%置信区间（95%CI）为0.32-0.83，以及OR为0.53；95%CI为0.29-0.95]。进一步分析显示，p21 CC/AT双倍型受试者的CBP发病几率降低（OR为0.51；95%CI为0.30-0.85）。此外，CBP工人或苯接触工人的p53 mRNA表达显著低于非接触工人。尽管这些结果需要进一步证实和拓展，但我们的结果表明，p21基因多态性可能对中国职业人群的CBP风险具有保护作用。
