The interaction effects of zinc and polygenic risk score with benzo[a]pyrene exposure on lung cancer risk : A prospective case-cohort study among Chinese populations
Copyright © 2024. Published by Elsevier Inc..
The relationship of exposure to benzo [a]pyrene (BaP) with lung cancer risk has been firmly established, but whether this association could be modified by other environmental or genetic factors remains to be explored. To investigate whether and how zinc (Zn) and genetic predisposition modify the association between BaP and lung cancer, we performed a case-cohort study with a 5.4-years median follow-up duration, comprising a representative subcohort of 1399 participants and 359 incident lung cancer. The baseline concentrations of benzo [a]pyrene diol epoxide-albumin adduct (BPDE-Alb) and Zn were quantified. We also genotyped the participants and computed the polygenic risk score (PRS) for lung cancer. Our findings indicated that elevated BPDE-Alb and PRS were linked to increased lung cancer risk, with the HR (95%CI) of 1.54 (1.36, 1.74) per SD increment in ln-transformed BPDE-Alb and 1.27 (1.14, 1.41) per SD increment in PRS, but high plasma Zn level was linked to a lower lung cancer risk [HR (95%CI) per SD increment in ln-transformed Zn = 0.77 (0.66, 0.91)]. There was evidence of effect modification by Zn on BaP-lung cancer association (P for multiplicative interaction = 0.008). As Zn concentrations increased from the lowest to highest tertile, the lung cancer risk per SD increment in ln-transformed BPDE-Alb decreased from 2.07 (1.48, 2.89) to 1.45 (1.03, 2.05) to 1.33 (0.90, 1.95). Additionally, we observed a significant synergistic interaction of BPDE-Alb and PRS [RERI (95%CI) = 0.85 (0.03, 1.67)], with 42% of the incident lung cancer cases among individuals with high BPDE-Alb and high PRS attributable to their additive effect [AP (95%CI) = 0.42 (0.14, 0.69)]. This study provided the first prospective epidemiological evidence that Zn has protective effect against BaP-induced lung tumorigenesis, whereas high genetic risk can enhance the harmful effect of BaP. These findings may provide novel insight into the environment-environment and environment-gene interaction underlying lung cancer development, which may help to develop prevention and intervention strategies to manage BaP-induced lung cancer.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Environmental research - (2024) vom: 22. Feb., Seite 118539 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fu, Ming [VerfasserIn] |
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| Links: |
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| Themen: |
Benzo[a]pyrene |
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| Anmerkungen: |
Date Revised 24.02.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.envres.2024.118539 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368916626 |
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| 100 | 1 | |a Fu, Ming |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The interaction effects of zinc and polygenic risk score with benzo[a]pyrene exposure on lung cancer risk |b A prospective case-cohort study among Chinese populations |
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| 520 | |a Copyright © 2024. Published by Elsevier Inc. | ||
| 520 | |a The relationship of exposure to benzo [a]pyrene (BaP) with lung cancer risk has been firmly established, but whether this association could be modified by other environmental or genetic factors remains to be explored. To investigate whether and how zinc (Zn) and genetic predisposition modify the association between BaP and lung cancer, we performed a case-cohort study with a 5.4-years median follow-up duration, comprising a representative subcohort of 1399 participants and 359 incident lung cancer. The baseline concentrations of benzo [a]pyrene diol epoxide-albumin adduct (BPDE-Alb) and Zn were quantified. We also genotyped the participants and computed the polygenic risk score (PRS) for lung cancer. Our findings indicated that elevated BPDE-Alb and PRS were linked to increased lung cancer risk, with the HR (95%CI) of 1.54 (1.36, 1.74) per SD increment in ln-transformed BPDE-Alb and 1.27 (1.14, 1.41) per SD increment in PRS, but high plasma Zn level was linked to a lower lung cancer risk [HR (95%CI) per SD increment in ln-transformed Zn = 0.77 (0.66, 0.91)]. There was evidence of effect modification by Zn on BaP-lung cancer association (P for multiplicative interaction = 0.008). As Zn concentrations increased from the lowest to highest tertile, the lung cancer risk per SD increment in ln-transformed BPDE-Alb decreased from 2.07 (1.48, 2.89) to 1.45 (1.03, 2.05) to 1.33 (0.90, 1.95). Additionally, we observed a significant synergistic interaction of BPDE-Alb and PRS [RERI (95%CI) = 0.85 (0.03, 1.67)], with 42% of the incident lung cancer cases among individuals with high BPDE-Alb and high PRS attributable to their additive effect [AP (95%CI) = 0.42 (0.14, 0.69)]. This study provided the first prospective epidemiological evidence that Zn has protective effect against BaP-induced lung tumorigenesis, whereas high genetic risk can enhance the harmful effect of BaP. These findings may provide novel insight into the environment-environment and environment-gene interaction underlying lung cancer development, which may help to develop prevention and intervention strategies to manage BaP-induced lung cancer | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Benzo[a]pyrene | |
| 650 | 4 | |a Genetic susceptibility | |
| 650 | 4 | |a Interaction | |
| 650 | 4 | |a Lung cancer | |
| 650 | 4 | |a Zinc | |
| 700 | 1 | |a Meng, Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Minghui |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Ziwei |e verfasserin |4 aut | |
| 700 | 1 | |a Guan, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Bai, Yansen |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Chenming |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Yuhan |e verfasserin |4 aut | |
| 700 | 1 | |a Hong, Shiru |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a He, Meian |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xiaomin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Chaolong |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Huan |e verfasserin |4 aut | |
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