Body mass index modulates aromatic DNA adduct levels and their persistence in smokers.
Body mass index modulates aromatic DNA adduct levels and their persistence in smokers.
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发表时间：
2002-08
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通讯作者：
R. Godschalk;Dorien E M Feldker;P. Borm;E. Wouters;F. V. van Schooten
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作者：
R. Godschalk;Dorien E M Feldker;P. Borm;E. Wouters;F. V. van Schooten
与体重平均的吸烟者相比，体重指数(BMI；体重/身高(2))低的吸烟者患肺癌的风险更高，但这一观察结果没有机制上的解释。香烟烟雾中的致癌物被认为是通过DNA加合物的形成而诱发癌症的，这为进一步研究BMI和肺癌之间的生物学联系提供了机会。24例健康吸烟志愿者外周血淋巴细胞DNA加合物水平(0.76+/-0.41个/10(8)核苷酸加合物)与吸烟呈正相关(r=0.51；P=0.01)，与BMI呈负相关(r=-0.48；P=0.02)。当这两个参数被纳入多元回归分析时，两者之间存在显著的总体关系(r=0.63；P=0.007)。此外，身体成分可能会影响DNA加合物的持久性，因为亲脂性烟草烟雾衍生的致癌物会在脂肪组织中积累，一旦暴露停止，就可以被动员起来。因此，在不吸烟22周后，对所有受试者的DNA加合物水平和BMI进行了重新评估。加合物水平下降到每10(8)个核苷酸0.44+/-0.23(P=0.002)，根据指数衰减到不吸烟对照组的本底水平(每10(8)个核苷酸0.33+/-0.18)，估计半衰期为11周。超重受试者(BMI和GT；25)戒烟后体重增加不大(体重增加的中位数为6%)，与体重指数较低和体重增加较高的人相比，他们的持续加合物水平更高(P=0.06)。总体而言，这些结果表明，瘦是影响DNA加合物形成的宿主易感因素，这可能是观察到的BMI和肺癌风险之间的关系的基础。
Smokers with a low body mass index (BMI; weight/height(2)) have a higher risk for developing lung malignancies as compared with smokers of average weight, but there is no mechanistic explanation for this observation. Carcinogens in cigarette smoke are thought to elicit cancer by the formation of DNA adducts, which give the opportunity to additionally investigate the biological link between BMI and lung cancer. DNA adduct levels in peripheral blood lymphocytes of 24 healthy smoking volunteers (0.76 +/- 0.41 adducts per 10(8) nucleotides) positively correlated with cigarette consumption (r = 0.51; P = 0.01) and were inversely related with BMI (r = -0.48; P = 0.02). A significant overall relationship was observed when both parameters were included in multiple regression analysis (r = 0.63; P = 0.007). Moreover, body composition may affect DNA adduct persistence, because lipophilic tobacco smoke-derived carcinogens accumulate in adipose tissue and can be mobilized once exposure ceases. Therefore, DNA adduct levels and BMI were reassessed in all of the subjects after a nonsmoking period of 22 weeks. Adduct levels declined to 0.44 +/- 0.23 per 10(8) nucleotides (P = 0.002), and the estimated half-life was 11 weeks on the basis of exponential decay to background levels in never-smoking controls (0.33 +/- 0.18 per 10(8) nucleotides). Overweight subjects (BMI >25) with little weight gain after smoking cessation (<median weight gain of 6%) had more persistent adduct levels as compared with those with lower BMI and higher weight gain (P = 0.06). Overall, these results suggest that leanness is a host susceptibility factor that affects DNA adduct formation, which could underlie the observed relationship between BMI and lung cancer risk.