Correlation analysis
Spearman correlation was applied to evaluate the association of the sociodemographic variables and oxidant and antioxidant parameters with OCP levels in patients with lung cancer (Table 3 and Table 4).
Table 3
Overall correlation among studied parameters of OCPs exposed subjects.
| AChE | PON1 | MDA | TAC | NO | PC | SOD3 | GPx3 | CAT | Age | BMI | α-HCH | β-HCH | γ-HCH | 2,4 DDE | 4,4 DDE | 2,4 DDT | 4,4 DDT |
AChE | 1.0 | 0.085 | -0.222 | 0.217 | -0.280* | -0.165 | -0.285* | 0.220 | 0.254 | 0.041 | -0.346* | -0.276 | -0.204 | -0.283* | -0.198 | -0.325* | -0.303* | -0.459** |
PON1 | - | 1.0 | -0.202 | 0.164 | -0.168 | -0.185 | 0.088 | 0.281* | 0.305* | 0.116 | -0.202 | -0.181 | -0.320* | -0.348* | -0.325* | -0.394** | -0.385** | -0.169 |
MDA | - | - | 1.0 | 0.135 | 0.230 | 0.287* | 0.105 | -0.246 | -0.314* | 0.083 | 0.297* | 0.088 | 0.268 | 0.095 | 0.327* | -0.096 | -0.020 | 0.461** |
TAC | - | - | - | 1.0 | .004 | -0.164 | -0.026 | 0.223 | 0.288* | 0.296* | -0.142 | -0.310* | -0.394** | -0.412** | -0.022 | -0.437** | -0.434** | -0.010 |
NO | - | - | - | - | 1.0 | 0.396** | 0.073 | -0.115 | -0.129 | -0.074 | 0.324* | -0.007 | 0.305* | 0.194 | 0.280* | 0.159 | 0.145 | 0.516** |
PC | - | - | - | - | - | 1.0 | 0.052 | -0.003 | -0.165 | -0.047 | 0.441** | 0.158 | 0.261 | 0.327* | 0.351* | 0.221 | -0.004 | 0.512** |
SOD3 | - | - | - | - | - | - | 1.0 | -0.271 | 0.035 | 0.126 | -0.045 | 0.020 | 0.082 | 0.173 | -0.114 | -0.010 | -0.064 | 0.112 |
GPx3 | - | - | - | - | - | - | - | 1.0 | 0.196 | 0.070 | -0.022 | -0.065 | -0.337* | -0.294* | -0.178 | -0.028 | -0.257 | -0.131 |
CAT | - | - | - | - | - | - | - | - | 1.0 | -0.061 | -0.439** | -0.086 | -0.261 | -0.335* | -0.200 | -0.288* | -0.107 | -0.461** |
Age | - | - | - | - | - | - | - | - | - | 1.0 | -0.053 | -0.214 | -0.336* | -0.009 | -0.010 | 0.048 | -0.388** | 0.040 |
BMI | - | - | - | - | - | - | - | - | - | - | 1.0 | 0.187 | 0.280* | 0.251 | 0.143 | 0.271 | 0.202 | 0.562** |
α-HCH | - | - | - | - | - | - | - | - | - | - | - | 1.0 | 0.544** | 0.333* | -0.022 | 0.596** | 0.522** | 0.053 |
β-HCH | - | - | - | - | - | - | - | - | - | - | - | - | 1.0 | 0.668** | 0.447** | 0.298* | 0.408** | 0.261 |
γ-HCH | - | - | - | - | - | - | - | - | - | - | - | - | - | 1.0 | 0.290* | 0.495** | 0.304* | 0.246 |
2,4 DDE | - | - | - | - | - | - | - | - | - | - | - | - | - | - | 1.0 | 0.064 | -0.031 | 0.401** |
4,4 DDE | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | 1.0 | 0.466** | 0.099 |
2,4 DDT | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | 1.0 | 0.009 |
4,4 DDT | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | 1.0 |
*. Spearman correlation is significant at the 0.05 level (2-tailed). |
**. Spearman correlation is significant at the 0.01 level (2-tailed). |
Eta co-efficient was used nominal variables. |
AChE: Acetylcholinesterase; PON1: Paraoxonase1; MDA: Malondialdehyde; TAC: Total antioxidant capacity. NO: Nitric oxide; PC: Protein carbonyl; SOD3: Superoxide dismutase3; GPx3: Glutathione peroxidase3; CAT: Catalase; α-HCH: α-Hexachlorocyclohexane; β-HCH: β-Hexachlorocyclohexane; γ-HCH: γ-Hexachlorocyclohexane; 2,4-DDE: 2,4-Dichlorodiphenyldichloroethylene; 4,4-DDE: 4,4-Dichlorodiphenyldichloroethylene; 2,4-DDT: 2,4-Dichlorodiphenyltrichloroethane; 4,4-DDT: 4,4-Dichlorodiphenyltrichloroethane. |
Table 4
Associations of OCPs with oxidative stress
| α-HCH | β-HCH | γ-HCH | 2,4 DDE | 4,4 DDE | 2,4 DDT | 4,4 DDT |
Slope | 95% CI | P-value | Slope | 95% CI | P-value | Slope | 95% CI | P-value | Slope | 95% CI | P-value | Slope | 95% CI | P-value | Slope | 95% CI | P-value | Slope | 95% CI | P-value |
AChE | -0.26 | -0.66-0.01 | 0.05 | -0.34 | -0.65--0.08 | 0.01 | -0.32 | -0.76--0.07 | 0.01 | -0.18 | -0.45-0.09 | 0.19 | -0.34 | -0.48--0.06 | 0.01 | -0.44 | -0.75--0.19 | 0.001 | -0.63 | -0.61--0.29 | <0.001 |
PON1 | -0.17 | -3.3-0.78 | 0.22 | -0.47 | -4.61--1.39 | <0.001 | -0.49 | -5.67--1.88 | <0.001 | -0.28 | -3.23--0.02 | 0.04 | -0.51 | -3.6--1.27 | <0.001 | -0.34 | -3.94--0.49 | 0.01 | -0.38 | -2.80--0.53 | 0.005 |
MDA | 0.11 | -0.16-0.38 | 0.42 | 0.36 | 0.07-0.53 | 0.009 | 0.14 | -0.14-0.43 | 0.3 | 0.42 | 0.12-0.53 | 0.002 | 0.02 | -0.16-0.19 | 0.88 | 0.14 | -0.11-0.36 | 0.3 | 0.59 | 0.20-0.47 | <0.001 |
TAC | -0.31 | -45.49--2.95 | 0.026 | -0.40 | -45.88--9.98 | 0.003 | -0.42 | -56.39--13.92 | 0.002 | 0.03 | -16.07-19.9 | 0.83 | -0.50 | -38.15--12.8 | <0.001 | -0.47 | -49.98--15.09 | <0.001 | -0.32 | -27.39--2.24 | 0.022 |
NO | -0.01 | -0.82-0.73 | 0.90 | 0.22 | -0.12-1.21 | 0.10 | 0.14 | -0.39-1.23 | 0.30 | 0.32 | 0.10-1.29 | 0.022 | 0.10 | -0.32-0.69 | 0.46 | 0.10 | -0.44-0.93 | 0.47 | 0.51 | 0.44-1.23 | <0.001 |
PC | 0.07 | -0.19-0.33 | 0.58 | 0.32 | 0.03-0.48 | 0.022 | 0.36 | 0.09-0.61 | 0.008 | 0.35 | 0.06-0.46 | 0.011 | 0.24 | -0.02-0.31 | 0.08 | 0.04 | -0.20-0.26 | 0.77 | 0.50 | 0.14-0.41 | <0.001 |
SOD3 | -0.07 | -4.07-2.39 | 0.60 | 0.03 | -2.55-3.14 | 0.83 | 0.04 | -2.91-3.89 | 0.77 | -0.11 | -3.58-1.59 | 0.44 | -0.06 | -2.59-1.63 | 0.64 | -0.05 | -3.41-2.31 | 0.70 | 0.08 | -1.35-2.47 | 0.56 |
GPx3 | -0.01 | -2.62-2.35 | 0.91 | -0.22 | -3.88-0.38 | 0.10 | -0.33 | -5.48--0.54 | 0.018 | -0.03 | -2.23-1.79 | 0.81 | -0.17 | -2.60-0.60 | 0.21 | -0.19 | -3.63-0.69 | 0.17 | -0.29 | -2.92--0.10 | 0.036 |
CAT | -0.17 | -17.53-3.95 | 0.21 | -0.31 | -19.46--1.23 | 0.027 | -0.38 | -25.82--4.62 | 0.006 | -0.13 | -12.82-4.57 | 0.34 | -0.37 | -15.83--2.57 | 0.007 | -0.37 | -21.42--3.49 | 0.007 | -59 | -18.62--8.22 | <0.001 |
AChE activity was inversely significantly associated with α-HCH, β-HCH, 4,4-DDE, 2,4 DDT, and 4,4 DDT. PON1 activity was inversely significantly associated with β-HCH, γ-HCH, 2,4 DDE, 4,4-DDE, 2,4 DDT, and 4,4 DDT. MDA was positivity significantly associated with β-HCH, 2,4 DDE, and 4,4 DDT. TAC was inversely significantly associated with α-HCH, β-HCH, γ-HCH, 4,4-DDE, 2,4-DDT, and 4,4 DDT. NO was directly significantly associated with 2,4 DDE and 2,4 DDT. PC was positivity significantly related to β-HCH, γ-HCH, 2,4 DDE, and 4,4 DDT. GPx3 activity was inversely significantly related to γ-HCH, and 4,4 DDT. CAT activity was inversely significantly associated with β-HCH, γ-HCH, 4,4-DDE, 2,4 DDT, and 4,4 DDT. |
a CI: confidence interval; Adjusted for BMI and total lipids. |
Table 3 presents the overall correlations between the studied parameters. As indicated by the results, AChE activity was negatively correlated with NO levels (r = -0.280; p < 0.05), SOD3 activity (r = -0.285; P < 0.05), and BMI (r = -0.346; P < 0.05). In addition, PON-1 had a significant positive correlation with GPx3 activity level (r = 0.281, P < 0.05) and CAT activity level (r = 0.305; P < 0.05). Moreover, MDA levels showed a significant positive association with PC levels (r = 0.287; P < 0.05) and BMI (r = 0.297; P < 0.01), and a negative correlation with CAT activity (r = -0.314; P < 0.05). TAC had a significant positive relationship with CAT activity (r = 0.288; P < 0.05) and age (r = 0.296; P < 0.05). NO was positively correlated with PC (r = 0.396; P < 0.01) and BMI (r = 0.324; P < 0.05). Furthermore, a negative significant correlation was seen between CAT activity and BMI (r = -0.439; P < 0.01).
In addition, the results indicated that γ-HCH (r = -0.283; P < 0.05), 4,4 DDE (r = -0.325; P < 0.05), 2,4 DDT (r = -0.303; P < 0.05), and 4,4 DDT (r = -0.459; P < 0.01) were negatively correlated with AChE activity. However, β-HCH (r = -0.320; P < 0.05), γ-HCH (r = -0.348; P < 0.05), 2,4 DDE (r = -0.325; P < 0.05), 4,4 DDE (r = -0.394; P < 0.01), and 2,4 DDT (r = -0.385; P < 0.01) had a negative correlation with PON-1 activity. Furthermore, 2,4 DDE (r = 0.327; P < 0.05) and 4,4 DDT (r = 0.461; P < 0.01) exhibited a positive significant association with MDA levels. Moreover, TAC had a significant negative correlation with α-HCH (r = -0.310; P < 0.05), β-HCH (r = -0.394; P < 0.01), γ-HCH (r = -0.412; P < 0.01), 4,4 DDE (r = -0.437; P < 0.01), and 2,4 DDT (r = -0.434; P < 0.01). Data also showed that the NO level had a direct significant relationship with β-HCH (r = 0.305; P < 0.05), 2,4 DDE (r = 0.280; P < 0.05), and 4,4 DDT (r = 0.516; P < 0.01). It was observed that the PC level was positively correlated with γ-HCH (r = 0.327; P < 0.05), 2,4 DDE (r = 0.351; P < 0.05), and 4,4 DDT (r = 0.512; P < 0.01). The GPx3 activity level had a significant negative relation with β-HCH (r = -0.437; P < 0.01) and γ-HCH (r = -0.437; P < 0.01). Moreover, γ-HCH (r = -0.335; P < 0.05), 4,4 DDE (r = -0.288; P < 0.05), and 4,4 DDT (r = -0.461; P < 0.01) had a significant negative correlation with the CAT activity level. Finally, age was shown to be negatively associated with β-HCH (r = -0.336; P < 0.05) and 2,4 DDT (r = -0.388; P < 0.01).
Table 4 demonstrates the correlation of oxidant and antioxidant parameters with OCP levels. Data showed a negative significant association between 4,4 DDE and AChE activity (P = 0.011). The results also indicated that NO and PC levels had a positive correlation with 2,4 DDT (P = 043) and 4,4 DDT (P = 0.003), respectively. However, MDA, TAC, PON-1, SOD, GPx, and CAT activity levels did not show any correlation with the measured OCP levels (P > 0.05).
To assess the effects of pesticide exposure on OS parameters, a linear regression analysis was used (Table 4). AChE activity showed a significant inverse relationship with α-HCH (β = -0.26, P = 0.05), β-HCH (β = -0.34, P = 0.01), γ-HCH (β = -0.32, P = 0.01), 4,4 DDE (β = -0.34, P = 0.01), 2,4 DDT (β = -0.44, P = 0.001), and 4,4 DDT (β = -0.63, P = 0.001). The regression results also showed that the PON-1 activity had an inverse significant association with β-HCH (β = -0.47, P < 0.001), γ-HCH (β = -0.49, P < 0.001), 2,4 DDE (β = -0.28, P = 0.04), 4,4-DDE (β = -0.51, P < 0.001), 2,4 DDT (β = -0.34, P = 0.01), and 4,4 DDT (β = -0.38, P = 0.005). TAC activity showed an inverse significant relationship with α-HCH (β = -0.31, P < 0.026), β-HCH (β = -0.40, P < 0.003), γ-HCH (β = -0.42, P = 0.002), 4,4 DDE (β = -0.50, P < 0.001), 2,4 DDT (β = -0.47, P < 0.001), and 4,4 DDT (β = -0.32, P = 0.022). Moreover, NO had a significant relationship with 2,4 DDE (β = 0.32, P = 0.022) and 4,4 DDT (β = 0.51, P = 0.001). GPx3 activity was shown to have an inverse relationship with γ-HCH (β = -0.33, P = 0.018) and 4,4 DDT (β = -0.29, P = 0.036). CAT activity also had an inverse relationship with β-HCH (β = -0.31, P = 0.027), γ-HCH (β = -0.38, P = 0.006), 4,4 DDE (β = -0.37, P = 0.007), 2,4 DDT (β = -0.37, P = 0.007), and 4,4 DDT (β = -0.59, P < 0.001).
MDA level had a positive significant association with β-HCH (β = 0.36, P = 0.009), 2,4 DDE (β = 0.42, P = 0.002), and 4,4 DDT (β = 0.59, P < 0.001). In addition, PC was positively associated with β-HCH (β = 0.32, P = 0.022), γ-HCH (β = 0.36, P = 0.008), 2,4 DDE (β = 0.35, P = 0.011), and 4,4-DDT (β = 0.50, P < 0.001). SOD3 activity had no significant association with OCPs.
Logistic regression analysis revealed that higher levels of OCPs were linked to an increased risk of lung cancer (Table 5). Moreover, analyses were adjusted for potential confounding factors, which included BMI, TG, and cholesterol. Lung cancer was associated with α-HCH (multivariable-adjusted OR = 3.19, 95% CI: 1.77-5.75, P < 0.001), β-HCH (OR = 5.68, 95% CI: 2.71-11.90, P < 0.001), γ-HCH (OR = 5.64, 95% CI: 2.55-12.47, P < 0.001), 2, 4 DDE (OR = 6.40, 95% CI: 2.93-13.94, P < 0.001), 4,4 DDE (OR = 3.80, 95% CI: 2.11-6.86, P < 0.001), 2, 4 DDT (OR = 5.13, 95% CI: 2.58-10.17, P < 0.001), and 4, 4 DDT (OR = 3.72, 95% CI: 2.71-6.39, P < 0.001).
Table 5
Association between lung cancer incidence and OCPs by quartiles.
| Crude | Adjusted |
| B | OR | CI-95% | P-value | B | OR | CI-95% | P-value |
α-HCH Q1(≤0.92) Q2(0.93-1.30) Q3(1.31-2.36) Q4(>2.36) p for trend | 0.27 Ref 0.97 1.04 1.68 | 1.31 2.64 2.85 5.40 | 19 – 1.44 0.94-7.40 0.92-8.80 1.58-18.39 | <0.001 0.064 0.068 0.007 | 1.16 Ref 1.63 0.94 1.72 | 3.19 5.12 2.56 5.59 | 1.77-5.75 1.39-18.74 0.67-9.79 1.31-23.80 | <0.001 0.014 0.16 0.02 |
β-HCH Q1(≤0.57) Q2(0.58-1.08) Q3(1.09-2.91) Q4(>2.91) p for trend | 0.43 Ref 0.51 1.53 1.80 | 1.53 1.66 4.64 6.07 | 1.31 – 1.79 0.51-5.39 1.46-14.76 1.96-18.72 | <0.001 0.39 0.009 0.002 | 1.73 Ref 1.38 2.97 2.76 | 5.68 3.97 19.50 15.87 | 2.71-11.90 0.81-19.53 3.25-116.8 3.45-72.94 | <0.001 0.,08 0.001 <0.001 |
γ-HCH Q1(≤0.35) Q2(0.36-1.22) Q3(1.23-2.14) Q4(>2.14) p for trend | 0.44 Ref -0.39 0.56 1.86 | 1.56 0.67 1.75 6.44 | 1.31 – 1.79 0.22-2.01 0.52-5.84 1.99-20.79 | <0.001 0.47 0.36 0.002 | 1.73 Ref -0.54 0.07 1.99 | 5.64 0.57 1.07 7.36 | 2.55-12.47 0.15-2.21 0.26-4.40 1.85-29.17 | <0.001 0.42 0.91 0.005 |
2,4-DDE Q1(≤0.95) Q2(0.96-1.72) Q3(1.73-2.62) Q4(>2.62) p for trend | 0.18 Ref 0.73 1.27 1.55 | 1.21 2.07 3.56 4.74 | 1.13 – 1.28 0.69-6.22 1.13-11.16 1.56-14.36 | <0.001 0.19 0.02 0.006 | 1.85 Ref 1.50 2.14 2.27 | 6.40 4.52 8.51 9.76 | 2.93-13.94 1.13-17.98 1.87-38.74 2.31-41.24 | <0.001 0.03 0.006 0.002 |
4,4-DDE Q1(≤0.86) Q2(0.87-1.62) Q3(1.63-4.27) Q4(>4.27) p for trend | 0.64 Ref 0.05 1.26 1.99 | 1.91 1.05 3.54 7.34 | 1.48 – 2.45 0.32-3.41 1.09-11.46 2.29-23.57 | <0.001 0.92 0.03 0.001 | 1.33 Ref 0.79 1.95 2.54 | 3.80 2.22 7.04 12.74 | 2.11-6.86 0.55-8.96 1.54-32.14 2.71-59.88 | <0.001 0.26 0.012 0.001 |
2,4-DDT Q1(≤1.36) Q2(1.37-1.64) Q3(1.65-3.77) Q4(>3.77) p for trend | 0.15 Ref 0.49 1.56 1.60 | 1.16 1.63 4.76 5.00 | 1.07 – 1.27 0.57-4.66 1.54-14.64 1.43-17.45 | <0.001 0.35 0.006 0.012 | 1.63 Ref 0.59 1.64 1.97 | 5.13 1.82 5.16 7.20 | 2.58-10.17 0.51-6.48 1.36-19.57 1.53-33.81 | <0.001 0.35 0.016 0.012 |
4,4-DDT Q1(≤1.42) Q2(1.43-2.33) Q3(2.34-4.61) Q4(>4.61) p for trend | 0.21 Ref 0.03 1.20 2.00 | 1.24 1.03 3.33 7.40 | 1.11 – 1.38 0.31-3.42 1.08-10.23 2.22-24.70 | <0.001 0.95 0.03 0.001 | 1.31 Ref 0.55 1.22 1.86 | 3.72 1.75 3.40 6.44 | 2.17-6.39 0.42-7.27 0.93-12.42 1.62-25.57 | <0.001 0.44 0.064 0.008 |
The estimation of the associations between lung cancer development and OCPs was performed by the continuous logistic regression model. a Adjusted for BMI and total lipids. Q: Quartile. Q was adjusted with age. OR: Odds ratio. |