Article Figures & Data
Figures
- Figure 1.
PLS-DA of all menthol and nonmenthol cigarette smokers. A, Three-dimensional score plot between the selected principle components (PC) showed difference between menthol (green) and nonmenthol (blue) smokers in their metabolomic profiles. B, Loadings plot showed MG as the most influential metabolite discriminating metabolome of menthol and nonmenthol smokers with an ANOVA assessment of the cross-validatory (CV) P = 0.0003. The P value indicates the probability level where a model with this F value may be the result of just chance.
- Figure 2.
Network associated with menthol boosts in menthol smokers. Yellow nodes, metabolites mapped from our study; magenta, seven molecules known as biomarkers for cancer.
Tables
- Table 1.
Study participant characteristics and differences between menthol and nonmenthol smokers
All (n = 105) Menthol (n = 71, 67.6%) Nonmenthol (n = 34, 32.4%) Variable n (%) Mean ± SD n (%) Mean ± SD n (%) Mean ± SD Pa Age (y) 43.1 ± 9.6 43.8 ± 9.3 41.4 ± 10.9 0.25 Age (y), categorical <44 yrs old 55 (52.4) 34 (47.9) 21 (61.8) 0.18 ≥44 yrs old 50 (47.6) 37 (52.1) 13 (38.2) Gender Male 67 (63.8) 43 (60.6) 24 (70.6) 0.32 Female 38 (36.2) 28 (39.4) 10 (29.4) Race AA 63 (60.0) 58 (81.7) 5 (14.7) <0.00001 EA 38 (36.2) 12 (16.9) 26 (76.5) Biracial 4 (3.8) 1 (1.4) 3 (8.8) Yrs smoked (y) 22.9 ± 9.9 22.5 ± 9.8 23.7 ± 10.3 0.57 Yrs smoked (y), categorical <22 yrs 52 (49.5) 39 (54.9) 13 (38.2) 0.11 ≥22 yrs 53 (50.5) 32 (45.1) 21 (61.8) Plasma cotinine (ng/mL) 252.6 ± 103.3 247.5 ± 97.3 263.4 ± 115.6 0.46 Plasma cotinine, categorical Low (<200) 35 (33.3) 23 (32.4) 12 (35.3) 0.96 Medium (200–279) 35 (33.3) 24 (33.8) 11 (32.4) High (>279) 35 (33.3) 24 (33.8) 11 (32.4) NMR 0.38 ± 0.22 0.37 ± 0.24 0.41 ± 0.17 0.44 NMR, categorical Q1 (<0.238) 25 (23.8) 20 (28.2) 5 (14.7) 0.25 Q2 (0.238–0.34) 27 (25.7) 19 (26.8) 8 (23.5) Q3 (0.341–0.458) 27 (25.7) 18 (25.4) 9 (26.5) Q4 (>0.458) 26 (24.8) 14 (19.7) 12 (35.3) FTND scoring 5.0 ± 2.3 4.8 ± 2.1 5.4 ± 2.7 0.20 FTND scoring, categorical <5 points 44 (41.9) 32 (45.1) 12 (35.3) 0.31 5–6 points 33 (31.4) 23 (32.4) 10 (29.4) >6 points 27 (25.7) 15 (21.1) 12 (35.3) Abbreviations: AA, African Americans; EA, European Americans.
↵aP values represent differences in menthol versus nonmenthol smokers for each characteristic. Continuous variables were evaluated by two-sample t tests (italics), and χ2 tests were used to investigate the differences in distributions of categorical variables from menthol to nonmenthol smokers.
- Table 2.
Correlation of the second MG boost to smoking-related variables
All smokers Menthol Nonmenthol ra Pa r P r P Average puff volume (mL) 0.36 0.0003 0.48 6.22E−05 0.09 0.64 CO boost 0.31 0.001 0.22 0.06 0.47 0.006 Average puff duration (sec) 0.30 0.003 0.33 0.008 0.10 0.58 Total smoke exposure (mL) 0.26 0.01 0.35 0.004 0.14 0.46 Nicotine boost 0.26 0.04 0.32 0.05 0.28 0.19 Average interpuff interval (sec) −0.14 0.17 −0.37 0.002 0.27 0.14 Number of puffs 0.11 0.27 0.17 0.18 0.07 0.69 Cotinine (ng/mL) 0.05 0.61 0.18 0.12 −0.15 0.40 Maximum puff velocity (mL/sec) 0.05 0.62 0.18 0.14 0.16 0.38 FTND 0.04 0.65 0.22 0.06 0.02 0.90 3HC (ng/mL) 0.04 0.69 0.23 0.06 −0.11 0.54 NMR 0.01 0.90 0.13 0.27 0.04 0.84 NOTE: Data significant at P < 0.05.
↵ar and P were computed on the basis of Spearman rank correlation coefficient.
- Table 3.
Differences in the smoking-related characteristics of participants from self-reported menthol and nonmenthol smokers in the study
Menthol (71) Nonmenthol (34) Fold change Mean ± SD Mean ± SD Pa (Menthol/nonmenthol) MG boost 31.2 ± 42.8 −2.78 ± 18.3 2.31E−05 11.2 Maximum puff velocity (mL/sec) 47.5 ± 13.7 51.6 ± 16.1 0.20 −1.1 FTND 4.8 ± 2.1 5.4 ± 2.7 0.20 −1.1 CO boost 5.2 ± 3.1 4.4 ± 3.6 0.20 1.2 3HC (ng/mL) 90.8 ± 67.9 106.7 ± 62.7 0.25 −1.2 Nicotine boost 14.0 ± 8.6 11.9 ± 7.0 0.31 1.2 NMR 0.4 ± 0.2 0.4 ± 0.2 0.44 −1.1 Average puff volume (mL) 55.7 ± 18.5 52.7 ± 18.0 0.45 1.1 Average puff duration (sec) 1.8 ± 0.6 1.6 ± 0.8 0.46 1.1 Cotinine (ng/mL) 247.5 ± 97.3 263.4 ± 115.6 0.46 −1.1 Average interpuff interval (sec) 20.0 ± 12.7 21.0 ± 14.7 0.74 −1.0 Number of puffs 12.6 ± 7.5 12.3 ± 6.6 0.87 1.0 Total smoke exposure (mL) 691.7 ± 455.9 690.3 ± 547.8 0.99 1.0 ↵aP value was computed on the basis of two-sample t tests. Data significant at P < 0.05.
- Table 4.
Known metabolites significantly correlated with MG boost among 71 menthol smokers
m/z RT Metabolites Adducts Category Δppm q-value PartialCorr 331.18 3.07 MG [M−H]− Prenol lipids 1 0.0040 0.53 640.29 5.52 S-(PGA2)-glutathione [M−H]− Carboxylic acids and derivatives 1 0.0042 −0.52 231.00 1.70 2,4-Dihydroxyacetophenone 5-sulfate [M−H]− Benzene and substituted derivatives 6 0.0199 0.42 205.10 0.36 l-Tryptophan [M+H]+ Indoles and derivatives 8 0.0288 0.53 167.02 0.34 Uric acid [M−H]− Alkaloids and derivatives 7 0.0344 0.39 187.01 1.71 Benzyl sulfate [M−H]− Organic sulfuric acids and derivatives 5 0.0344 0.42 462.30 5.01 PC(O-12:0/O-1:0) [M+Na]+ Glycerophospholipids 4 0.0344 −0.54 799.48 4.65 Thalicoside A [M+H]+ Terpenoids 7 0.0344 −0.54 460.28 4.63 PE(P-16:0/0:0) [M+Na]+ Glycerophospholipids 6 0.0364 −0.54 185.08 4.74 2-(1-Ethoxyethoxy)propanoic acid [M+Na]+ Carboxylic acids and derivatives 7 0.0397 −0.53 585.27 3.95 Bilirubin [M+H]+ Tetrapyrroles and derivatives 0 0.0408 0.52 189.00 1.71 Oxalosuccinic acid [M−H]− Carboxylic acids and derivatives 2 0.0472 0.41 792.60 8.48 PC(O-16:0/22:6) [M+H]+ Glycerophospholipids 8 0.0480 0.49 567.27 4.87 2-deoxy-20-hydroxyecdysone 22-phosphate [M+H]+ Sterol lipids 0 0.0485 −0.50 240.10 4.73 N-Ornithyl-L-taurine [M+H]+ Carboxylic acids and derivatives 3 0.0491 −0.49 313.27 4.85 10-oxo-nonadecanoic acid [M+H]+ Fatty acyls 0 0.0491 −0.51 481.32 5.00 20-hydroxyecdysone [M+H]+ Sterol lipids 2 0.0491 −0.52 505.35 5.03 Isothankunic acid [M+H]+ Prenol lipids 7 0.0491 −0.51 834.60 8.73 PC(22:2/16:1) [M+Na]+ Glycerophospholipids 1 0.0491 0.45 544.34 5.03 LysoPC(20:4) [M+H]+ Glycerophospholipids 0 0.0498 −0.48 *q-value (corrected P value) was computed on the basis of two-way ANCOVA model adjusted for gender, race, and cotinine levels. Data significant at q < 0.05 after correcting for multiple testing. PartialCorr represents the correlation between the second MG boost and the metabolites.
Abbreviations: m/z, mass-to-charge ratio; RT, retention time.
Supplementary Data
- Supplemental table 1 - Correlation of the significant metabolite boosts from the 2nd cigarette to smoking-related variables.
- Supplemental table 2 - Models determining the correlations of the MG boost to smoking-related variables.
- Supplemental table 3 - Correlation of pre- and post-cigarette MG levels to topography profiles.
- Supplemental table 4 - Correlation of the 2nd nicotine boost to smoking-related variables.
- Supplemental table 5 - Correlation of the 2nd CO boost to smoking-related variables.
- Supplemental figure 1 - Significant correlations of the 2nd MG boost to smoking-related variables.
Volume 26, Issue 1
