Contribution of genetic and nutritional factors to DNA damage in heavy smokers.
Contribution of genetic and nutritional factors to DNA damage in heavy smokers.
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遗传和营养因素对重度吸烟者 DNA 损伤的影响。
DOI：
10.1093/carcin/18.3.503
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发表时间：
1997
期刊：
影响因子：
4.7
通讯作者：
Perera,FP
中科院分区：
文献类型：
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作者：
Mooney,LA;Bell,DA;Santella,RM;VanBennekum,AM;Ottman,R;Paik,M;Blaner,WS;Lucier,GW;Covey,L;Young,TL;Cooper,TB;Glassman,AH;Perera,FP
先前的流行病学证据表明，控制致癌物代谢和抗氧化/营养状态的基因与肺癌风险相关，可能是通过它们调节致癌物对DNA损伤的能力。我们对参加戒烟计划的159名重度吸烟者进行了横断面分析。共分析了159份血液样本，以确定遗传多态性[CYP 1A 1 MspI和外显子7和谷胱甘肽S-转移酶M1（GSTM 1）]和血浆微量营养素对多环芳烃-DNA（PAH-DNA）加合物水平的相对贡献。吸烟者的DNA损伤受遗传多态性和营养状况的影响。携带CYP 1A 1外显子7缬氨酸多态性的吸烟者DNA损伤水平显著高于不携带CYP 1A 1外显子7缬氨酸多态性的吸烟者（2倍，P <或= 0.03）。在平行模型中，在159名受试者中，PAH-DNA加合物与血浆视黄醇（β =-0.93，P = 0.01）、β-胡萝卜素（β =-0.18，P = 0.09）和α-生育酚（β =-0.28，P = 0.21）水平呈负相关。吸烟调整后的血浆β-胡萝卜素水平与DNA损伤之间的相关性仅在缺乏GSTM 1解毒基因的受试者中显着（β =-0.30，P = 0.05，n = 75）。β-胡萝卜素和α-生育酚之间存在统计学相互作用;当β-胡萝卜素较低时，α-生育酚对加合物具有显著的保护作用（β =-0.78，P = 0.04），但当β-胡萝卜素较高时（β =-0.16，P = 0.57）。血浆α-生育酚与β-胡萝卜素显著相关（r = 0.36，P = 0.0005），与视黄醇不太相关（r = 0.20，P = 0.0005）。这些结果表明，几种微量营养素可能共同作用，以防止DNA损伤，并强调评估整体抗氧化状态的重要性。总之，由于低血浆微量营养素和遗传易感性因素的综合作用，吸烟者的一个子集可能处于DNA损伤和可能的肺癌的风险增加。鉴于目前关于在高危人群中使用化学预防剂的辩论，使用生物标志物来评估干预措施的有效性和研究微量营养素的机制是及时的。
Prior epidemiological evidence suggests that genes controlling the metabolism of carcinogens and antioxidant/nutritional status are associated with lung cancer risk, possibly through their ability to modulate DNA damage by carcinogens. We performed a cross-sectional analysis of 159 heavy smokers from a cohort of subjects enrolled in a smoking cessation program. A total of 159 blood samples were analyzed to determine the relative contributions of genetic polymorphisms [CYP1A1 MspI and exon 7 and glutathione S-transferase M1 (GSTM1)] and plasma micronutrients to polycyclic aromatic hydrocarbon-DNA (PAH-DNA) adduct levels. DNA damage in smokers was affected by genetic polymorphisms and nutritional status. Smokers with the CYP1A1 exon 7 valine polymorphism had significantly higher (2-fold, P < or = 0.03) levels of DNA damage than those without. In parallel models, PAH-DNA adducts were inversely associated with plasma levels of retinol (beta = -0.93, P = 0.01), beta-carotene (beta = -0.18, P = 0.09), and alpha-tocopherol (beta = -0.28, P = 0.21) in 159 subjects. The association between smoking-adjusted plasma beta-carotene levels and DNA damage was only significant in those subjects lacking the GSTM1 detoxification gene (beta = -0.30, P = 0.05, n = 75). There was a statistical interaction between beta-carotene and alpha-tocopherol; when beta-carotene was low, alpha-tocopherol had a significant protective effect (beta = -0.78, P = 0.04) on adducts, but not when beta-carotene was high (beta = -0.16, P = 0.57). Plasma alpha-tocopherol was significantly correlated with beta-carotene (r = 0.36, P = 0.0005) and less strongly with retinol (r = 0.20, P = 0.0005). These results suggest that several micronutrients may act in concert to protect against DNA damage and highlight the importance of assessing overall antioxidant status. In conclusion, a subset of smokers may be at increased risk of DNA damage and possibly lung cancer due to the combined effect of low plasma micronutrients and genetic susceptibility factors. The use of biological markers to assess efficacy of interventions and to study mechanisms of micronutrients is timely given the current debate regarding the use of chemopreventive agents in high risk populations.