Joint Effects of Polycyclic Aromatic Hydrocarbons, Smoking, and XPC Polymorphisms on Damage in Exon 2 of KRAS Gene Among Young Coke Oven Workers

Overview

Journal Front Public Health

Specialty Public Health

Date 2022 Aug 22

PMID 35991047

Authors

Siqin Chen

Xingyue Yin

Yuefeng He

Qinghua He

Xiaomei Li

Maosheng Yan

Suli Huang

Jiachun Lu

Binyao Yang

Affiliations

Soon will be listed here.

Abstract

Genetic polymorphisms may contribute to individual susceptibility to DNA damage induced by environmental exposure. In this study, we evaluate the effects of co-exposure to PAHs, smoking and XPC polymorphisms, alone or combined, on damage in exons. A total of 288 healthy male coke oven workers were enrolled into this study, and urinary 1-hydroxypyrene (1-OH-Pyr) was detected. Base modification in exons of KRAS and BRAF gene, and polymorphisms of XPC were determined in plasma by real-time PCR. We observed 1-OH-Pyr was positively related to damage in exon 2 of KRAS (KRAS-2) and in exon 15 of BRAF (BRAF-15), respectively, and KRAS-2 and BRAF-15 were significantly associated with increased 1-OH-Pyr. A stratified analysis found 1-OH-Pyr was significantly associated with KRAS-2 in both smokers and non-smokers, while 1-OH-Pyr was significantly associated with BRAF-15 only in smokers. Additionally, individuals carrying both rs2228001 G-allele (GG+GT) and rs3731055 GG homozygote (GG) genotype appeared to have more significant effect on KRAS-2. The high levels of 1-OH-Pyr were associated with KRAS-2 only in rs2228001 GG+GT genotype carriers and the high levels of 1-OH-Pyr were associated with KRAS-2 only in rs3731055 GG genotype carriers and the most severe KRAS-2 was observed among subjects carrying all four of the above risk factors. Our findings indicated the co-exposure effect of PAHs and smoking could increase the risk of KRAS-2 by a mechanism partly involving XPC polymorphisms.

References

Chen S, He Y, Yan M, Zhou Y, He Q, Tan J . The interaction effects of FEN1 rs174538 polymorphism and polycyclic aromatic hydrocarbon exposure on damage in exon 19 and 21 of EGFR gene in coke oven workers. Environ Sci Pollut Res Int. 2021; 28(43):60692-60703. DOI: 10.1007/s11356-021-15013-y. View

Czarny P, Kwiatkowski D, Toma M, Kubiak J, Sliwinska A, Talarowska M . Impact of Single Nucleotide Polymorphisms of Base Excision Repair Genes on DNA Damage and Efficiency of DNA Repair in Recurrent Depression Disorder. Mol Neurobiol. 2016; 54(6):4150-4159. PMC: 5509815. DOI: 10.1007/s12035-016-9971-6. View

Ferrara M, Di Noia V, DArgento E, Vita E, Damiano P, Cannella A . Oncogene-Addicted Non-Small-Cell Lung Cancer: Treatment Opportunities and Future Perspectives. Cancers (Basel). 2020; 12(5). PMC: 7281569. DOI: 10.3390/cancers12051196. View

Singh A, Kamal R, Ahamed I, Wagh M, Bihari V, Sathian B . PAH exposure-associated lung cancer: an updated meta-analysis. Occup Med (Lond). 2018; 68(4):255-261. DOI: 10.1093/occmed/kqy049. View

Lee G, Jang J, Lee S, Jeon H, Kim K, Choi J . XPC polymorphisms and lung cancer risk. Int J Cancer. 2005; 115(5):807-13. DOI: 10.1002/ijc.20900. View

Sikorsky J, Primerano D, Fenger T, Denvir J . DNA damage reduces Taq DNA polymerase fidelity and PCR amplification efficiency. Biochem Biophys Res Commun. 2007; 355(2):431-7. PMC: 1945218. DOI: 10.1016/j.bbrc.2007.01.169. View

Liu Y, Li H, Zhu J, Zhang Y, Liu X, Li R . The Prevalence and Concurrent Pathogenic Mutations of in Northeast Chinese Non-small-cell Lung Cancer Patients. Cancer Manag Res. 2021; 13:2447-2454. PMC: 7979353. DOI: 10.2147/CMAR.S282617. View

Zhang X, He N, Gu D, Wickliffe J, Salazar J, Boldogh I . Genetic Evidence for XPC-KRAS Interactions During Lung Cancer Development. J Genet Genomics. 2015; 42(10):589-596. PMC: 4643398. DOI: 10.1016/j.jgg.2015.09.006. View

Paris C, Do P, Mastroianni B, Dixmier A, Dumont P, Pichon E . Association between lung cancer somatic mutations and occupational exposure in never-smokers. Eur Respir J. 2017; 50(4). DOI: 10.1183/13993003.00716-2017. View

10.

Hansen A, Mathiesen L, Pedersen M, Knudsen L . Urinary 1-hydroxypyrene (1-HP) in environmental and occupational studies--a review. Int J Hyg Environ Health. 2008; 211(5-6):471-503. DOI: 10.1016/j.ijheh.2007.09.012. View

11.

Yamano Y, Hara K, Ichiba M, Hanaoka T, Pan G, Nakadate T . Urinary 1-hydroxypyrene as a comprehensive carcinogenic biomarker of exposure to polycyclic aromatic hydrocarbons: a cross-sectional study of coke oven workers in China. Int Arch Occup Environ Health. 2013; 87(7):705-13. DOI: 10.1007/s00420-013-0913-6. View

12.

Ferrer I, Zugazagoitia J, Herbertz S, John W, Paz-Ares L, Schmid-Bindert G . KRAS-Mutant non-small cell lung cancer: From biology to therapy. Lung Cancer. 2018; 124:53-64. DOI: 10.1016/j.lungcan.2018.07.013. View

13.

Gou L, Niu F, Wu Y, Zhong W . Differences in driver genes between smoking-related and non-smoking-related lung cancer in the Chinese population. Cancer. 2015; 121 Suppl 17:3069-79. DOI: 10.1002/cncr.29531. View

14.

de Oliveira Alves N, Pereira G, Di Domenico M, Costanzo G, Benevenuto S, de Oliveira Fonoff A . Inflammation response, oxidative stress and DNA damage caused by urban air pollution exposure increase in the lack of DNA repair XPC protein. Environ Int. 2020; 145:106150. DOI: 10.1016/j.envint.2020.106150. View

15.

Uras I, Moll H, Casanova E . Targeting Mutant Non-Small-Cell Lung Cancer: Past, Present and Future. Int J Mol Sci. 2020; 21(12). PMC: 7352653. DOI: 10.3390/ijms21124325. View

16.

Maitre A, Petit P, Marques M, Herve C, Montlevier S, Persoons R . Exporisq-HAP database: 20 years of monitoring French occupational exposure to polycyclic aromatic hydrocarbon mixtures and identification of exposure determinants. Int J Hyg Environ Health. 2018; 221(2):334-346. DOI: 10.1016/j.ijheh.2017.12.008. View

17.

Riely G, Marks J, Pao W . KRAS mutations in non-small cell lung cancer. Proc Am Thorac Soc. 2009; 6(2):201-5. DOI: 10.1513/pats.200809-107LC. View

18.

Han F, Guo H, Hu J, Zhang J, Ying Q, Zhang H . Sources and health risks of ambient polycyclic aromatic hydrocarbons in China. Sci Total Environ. 2019; 698:134229. DOI: 10.1016/j.scitotenv.2019.134229. View

19.

Hainaut P, Pfeifer G . Patterns of p53 G-->T transversions in lung cancers reflect the primary mutagenic signature of DNA-damage by tobacco smoke. Carcinogenesis. 2001; 22(3):367-74. DOI: 10.1093/carcin/22.3.367. View

20.

Quezada-Maldonado E, Sanchez-Perez Y, Chirino Y, Garcia-Cuellar C . Airborne particulate matter induces oxidative damage, DNA adduct formation and alterations in DNA repair pathways. Environ Pollut. 2021; 287:117313. DOI: 10.1016/j.envpol.2021.117313. View