Centre for Addiction and Mental Health and Department of Pharmacology and Toxicology, University of Toronto, Ontario, Canada.
Cancer Epidemiol Biomarkers Prev. 2009 Dec;18(12):3426-34. doi: 10.1158/1055-9965.EPI-09-0956.
Although expired carbon monoxide (CO) and plasma cotinine (COT) have been validated as biomarkers of self-reported cigarettes per day (CPD) in heavy smoking Caucasians, their utility in light smokers is unknown. Further, variability in CYP2A6, the enzyme that mediates formation of COT from nicotine and its metabolism to trans-3'-hydroxycotinine (3HC), may limit the usefulness of COT. We assessed whether CO and COT are correlated with CPD in African-American light smokers (< or =10 CPD, n = 700), a population with known reduced CYP2A6 activity and slow COT metabolism. We also examined whether gender, age, body mass index, smoking mentholated cigarettes, or rate of CYP2A6 activity, by genotype and phenotype measures (3HC/COT), influence these relationships. At baseline, many participants (42%) exhaled CO of < or =10 ppm, the traditional cutoff for smoking, whereas few (3.1%) had COT below the cutoff of < or =14 ng/mL; thus, COT seems to be a better biomarker of smoking status in this population. CPD was weakly correlated with CO and COT (r = 0.32-0.39, P < 0.001), and those reporting fewer CPD had higher CO/cigarette and COT/cigarette, although the correlations coefficients between these variables were also weak (r = -0.33 and -0.08, P < 0.05). The correlation between CPD and CO was not greatly increased when analyzed by CYP2A6 activity, smoking mentholated cigarettes, or age, although it appeared stronger in females (r = 0.38 versus 0.21, P < 0.05) and obese individuals (r = 0.38 versus 0.24, P < 0.05). Together, these results suggest that CO and COT are weakly associated with self-reported cigarette consumption in African-American light smokers, and that these relationships are not substantially improved when variables previously reported to influence these biomarkers are considered.
尽管已验证过期的一氧化碳(CO)和血浆可替宁(COT)可作为重度吸烟白种人群自我报告的每日香烟量(CPD)的生物标志物,但它们在轻度吸烟者中的效用尚不清楚。此外,细胞色素 P450 2A6(CYP2A6)的变异性,该酶介导尼古丁形成 COT 及其代谢为反式-3'-羟基可替宁(3HC),可能限制了 COT 的有用性。我们评估了 CO 和 COT 是否与非裔美国轻吸烟者(<或=10 CPD,n=700)的 CPD 相关,该人群已知 CYP2A6 活性降低且 COT 代谢缓慢。我们还检查了性别、年龄、体重指数、吸烟薄荷醇香烟或通过基因型和表型测量(3HC/COT)的 CYP2A6 活性率是否会影响这些关系。在基线时,许多参与者(42%)呼出的 CO 低于<或=10 ppm,这是吸烟的传统临界值,而很少有参与者(3.1%)的 COT 低于<或=14 ng/mL;因此,在该人群中,COT 似乎是吸烟状态的更好生物标志物。CPD 与 CO 和 COT 呈弱相关(r=0.32-0.39,P<0.001),报告吸烟量较少的人 CO/支和 COT/支更高,尽管这些变量之间的相关系数也较弱(r=-0.33 和-0.08,P<0.05)。当按 CYP2A6 活性、吸烟薄荷醇香烟或年龄进行分析时,CPD 与 CO 的相关性并没有大大增加,尽管在女性中似乎更强(r=0.38 与 0.21,P<0.05)和肥胖者中更强(r=0.38 与 0.24,P<0.05)。总的来说,这些结果表明,CO 和 COT 与非裔美国轻吸烟者自我报告的香烟消耗量弱相关,并且当考虑到先前报道会影响这些生物标志物的变量时,这些关系并没有得到实质性改善。