Chunyan Wang, Lifang Liu, Xiaoli Liu, Wenjun Chen, and Guoping He＊

1Xiangya Nursing School, Central South University, Changsha 410013, China

2Organ Transplant Department, Third Xiangya Hospital, Central South University, Changsha 410013, China

Mechanisms of Lung Cancer Caused By Cooking Fumes Exposure: A Minor Review△

Chunyan Wang1, Lifang Liu2, Xiaoli Liu1, Wenjun Chen1, and Guoping He1＊

1Xiangya Nursing School, Central South University, Changsha 410013, China

2Organ Transplant Department, Third Xiangya Hospital, Central South University, Changsha 410013, China

cooking fumes exposure; lung cancer; toxic mechanisms

Cooking fumes (CFs) are mixtures of many toxic components, such as aldehydes,heterocyclic amines, polycyclic aromatic hydrocarbons, fat aerosols and particulate matters. CFs exposure has been proven to be associated with many diseases. Lung cancer takes the leading place among the diseases being reported caused by CFs exposure. Molecular and biochemical studies have found that CFs exposure may lead to lung cancer by gene damage, formation of reactive oxygen species, blockage of related proteins’ function,and even cell death. However, reviews about the mechanisms of how CFs exposure leads to lung cancer are still lacking. Elucidation of the mechanisms of lung cancer caused by CFs exposure may provide a new insight into the prevention of lung cancer caused by CFs exposure, as well as laying the foundation for the toxicity study of CFs. In this minor review, the mechanisms of how CFs exposure leads to lung cancer were summarized and discussed.

C OOKING fumes (CFs) are mainly produced during cooking fuels burning, cooking oil volatilization and reaction during heating process, the reaction between food and cooking oil.1-3CFs are mixture of many components, and the composition of CFs may depend on the kinds of food, the kinds of cooking oil and the cooking method.4Though the composition of CFs may be varied, it always contains many toxic components such as aldehydes, heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs), fat aerosols and particulate matters (PM).1,5-6

The production of CFs was recognized as the main source of indoor air pollution.7Due to the complex toxic compounds in CFs, CFs exposure may lead to lung toxicity,immune toxicity, hereditary toxicity, potential carcinogenicity, and so on. According to the World Health Organization (WHO), nearly 3% of the global burden of diseases(approximately 1.6 million excess deaths annually) was caused by human-based combustion activities such ascooking and heating.8Among the diseases caused by CFs exposure, lung cancer was the most reported one.3,9-16Many studies have demonstrated the relationship between CFs exposure and lung cancer. The mechanisms of lung cancer caused by CFs exposure were also investigated in several studies. However, reviews about the mechanisms of how CFs exposure leads to lung cancer are still lacking.

Elucidation of the mechanisms of lung cancer caused by CFs exposure may provide new methods to prevent lung cancer caused by CFs exposure. It can also provide the foundation for the toxicity study of CFs. In this review, the effects of CFs on lung cancer were summarized and discussed.

MECHANISMS OF HOW COOKING FUMES EXPOSURE LEADS TO LUNG CANCER

CFs exposure had been proven to be associated with the increased risk of lung toxicity, immune toxicity, hereditary toxicity, potential carcinogenicity, and so on,7,14,17among which, the relationship between lung cancer and CFs exposure was studied most intensively. The association between lung cancer and CFs exposure has been proven in several epidemiologic studies.18Molecular and biochemical studies have found many toxic components in CFs that may lead to gene damage and lung carcinogenesis(Fig. 1). In addition, CFs exposure is related to the formation of reactive oxygen species (ROS), the blockage of related proteins’ function, and even cell death (Fig. 1). Particularly fine particulate matter (PM2.5) of CFs could penetrate into the lungs readily, which would increase the incidence of respiratory and cardiovascular diseases.19

Cooking fumes exposure leads to lung cancer by gene damage

Many components in CFs are carcinogenic, especially the components of PAHs, aromatic hydrocarbons and HCAs.20Genotoxic studies showed that CFs own the ability to induce gene mutations in bacteria, oxidation of DNA bases,single stranded DNA cleavage, sister chromatid exchange and DNA cross-links.17,20

Cooking fumes exposure leads to lung cancer by affecting the function of DNA repair system

In human genomes, there is an important system named DNA repair system, which plays an important role in the maintenance of genomic integrity, and protecting the human genomes from damage by environmental carcinogens.Genetic variations in DNA repair genes could affect DNA repair capacity and lead to higher risk of lung cancer.21The human 8-oxoguanine DNA glycosylase 1 (hOGG1), apurinic/apyrimidinic endonuclease 1 (APE1), and adenosine diphosphate ribosyl transferase (ADPRT) genes are among the most important DNA base excision repair genes. Xueet al22studied the effect of these genes polymorphisms combined with CFs exposure on the risk of lung adenocarcinoma in Chinese non-smoking females. Their study indicated that the hOGG1 Ser326Cys polymorphism showed to be associated with the risk of lung adenocarcinoma. In addition, significant gene-environment association between CFs exposure and hOGG1 326Cys/Cys genotype was found in lung adenocarcinoma among female non-smokers. Yinet al23studied the association between single nucleotide polymorphisms of DNA repair genes and the risk of lung adenocarcinoma, and the stratified analysis suggested that increased risk associated with ERCC2 751 variant genotypes (AC/CC)was more pronounced in individuals without exposure to cooking oil fume (OR1.98, 95%CI1.18-3.32) and those without exposure to fuel smoke (OR2.47, 95%CI1.46-4.18). Urinary 8-OHdG is an important repair product through the base excision repair pathway.24The measurement of urinary 8-OHdG is useful in evaluating the risk of lung cancer. By the measurement of urinary 8-OHdG,Panet al25found CFs exposure could lead to oxidative DNA damage. Furthermore, oxidative stress response of female restaurant workers was greater than male restaurant workers.Cooking fumes exposure leads to lung cancer by affecting the function of miRNAs

Figure 1.Mechanisms of lung cancer caused by cooking fumes exposure.

MicroRNAs (miRNAs) are of the class of noncoding RNAs,approximately 20 nucleotides in length, which play an important role in the pathogenesis of human lung cancer.26Yinet al9investigated the effect of polymorphisms of premiRNA genes and cooking oil fume exposure on the risk of lung cancer. They found the combination of the five risk genotypes of miRNA Single Nucleotide Polymorphisms(SNPs) (miR-146a rs2910164, miR-196a2 rs11614913,miR-608 rs4919510, miR-27a rs895819 and miR-423 rs6505162) with the risk factor (cooking oil fume exposure)contributed to a significantly higher risk of lung cancer.

Cooking fumes exposure leads to lung cancer by blocking the function of related proteins

There are many kinds of proteins that playing important roles in regulating cellular function or DNA repair. These proteins play important roles in various diseases such as cancer. Many studies demonstrated that exposure to CFs might lead to polymorphism of such proteins, thus affecting the function of them. Among these proteins, X-ray repair cross-complementing group 1 (XRCC1) protein plays an important role in DNA repair.27In the study of Liet al,13they investigated the relationship among XRCC1 polymorphisms, CFs exposure and lung cancer. They found that,CFs exposure was associated with lung cancer, and XRCC1 Arg399Gln and T-77C polymorphisms may alter the risk of lung cancer in female nonsmokers in China. Another important protein of glutathione S-transferases also plays an important role in regulating cellular functions. Phukanet al11investigated the relationship among household exposure, dietary habits, glutathione S-transferases M1, T1 polymorphisms, and the risk of lung cancer. They found CFs exposure was significantly associated with an increased risk of lung cancer. Significant correlation was also observed for interaction of glutathione S-transferases polymorphisms with some of dietary habits.

Cooking fumes exposure leads to lung cancer by affecting cell viability

Many toxic components in CFs were related to the formation of ROS and the induction of cellular events resulting in cell death.8PAHs of CFs especially have carcinogenic properties on mucosal and endothelial lining of the upper aerodigestive tract.28According to the study of Wu and Yen,17the compounds of trans-trans-2,4-decadienal, t-t-2,4-DDE in CFs might induct ROS to human lung carcinoma pulmonary type II-like epithelium cells. Caoet al29also demonstrated that, with CFs exposure, the viability of lung type Ⅱ-like epithelium cells decreased in a dose- and timedependent manner. Cell cycles of lung type Ⅱ-like epithelium cells were disturbed by CFs exposure at a low concentration. Similarly, Cheet al30also found CFs can lead to apoptosisviamitochondrial and death receptor pathways in alveolar epithelial type Ⅱ cells. In addition, particularly PM2.5 of CFs could penetrate into the lungs readily, which would directly lead to the death of cells.19

Cooking fumes exposure leads to lung cancer by direct invasion to organs

The evaporated oil, PM and many other macromolecules in CFs could enter respiratory system directly with the contact of breath. When these components go through the respiratory system, some of them may deposit and attach to the surface of respiratory system, which in turn will affect the function of respiratory system. Once these components attach to the surface of respiratory system, they might discourage the gas exchange between the pneumocytes and gas in lung. These would lead to respiratory system diseases such as lung cancer finally.

PROSPECTS

CFs are mixtures of many toxic components, which is a main source of indoor air pollution. Due to the toxic components in CFs, CFs exposure has been proved to be associated with the increased risk of lung toxicity, immune toxicity, hereditary toxicity potential carcinogenicity and so on.Among which, lung cancer caused by CFs exposure was most studied. The mechanisms of lung cancer caused by CFs exposure were also studied in several published papers.However, further research about how CFs exposure leads to lung cancer is still needed. In addition, the relationship between CFs exposure and lung cancers has been widely studied. However, the relationships between CFs exposure and other systemic diseases (e.g. blood circulation system,immune system, reproductive system) are less studied.Due to the strong toxic impact of CFs exposure on organs,more studies about the toxic impact, impact mechanism and disposal methods of CFs need to be carried out.

Conflict of Interest Statement

The authors have no conflict of interests to disclose.

1. Yu KP, Yang KR, Chen YC, Gong JY, Chen YP, Shih HC,et al. Indoor air pollution from gas cooking in five Taiwanese families. Build Environ 2015; 93(Part 2):258-66. doi:10.1016/j.buildenv.2015.06.024.

2. Park SS, Kang MS, Hwang J. Oil mist collection and oil mist-to-gas conversionviadielectric barrier discharge at atmospheric pressure. Sep Purif Technol 2015; 151(4):324-31. doi: 10.1016/j.seppur.2015.07.059.

3. Kim C, Gao YT, Xiang YB, Barone-Adesi F, Zhang YW, Hosgood HD, et al. Home kitchen ventilation, cooking fuels,and lung cancer risk in a prospective cohort of never smoking women in Shanghai, China. Int J Cancer 2015;136(3):632-8. doi: 10.1002/ijc.29020.

4. Liao L, Liu HT, Zhang BL. Biodegradability of pollutants from cooking fumes. Bull Environ Contam Toxicol 2009;82(4):428-34. doi: 10.1007/s00128-008-9595-2.

5. Kabir E, Kim KH. An investigation on hazardous and odorous pollutant emission during cooking activities. J Hazard Mater 2011; 188(1-3):443-54. doi: 10.1016/j.jhazmat.2011.01.113.

6. Yao ZL, Li J, Wu BB, Hao XW, Yin Y, Jiang X. Characteristics of PAHs from deep-frying and frying cooking fumes. Environ Sci Pollut Res Int 2015; 22(20):16110-20. doi:10.1007/s11356-015-4837-4.

7. Wu CC, Bao LJ, Guo Y, Li SM, Zeng EY. Barbecue fumes:an overlooked source of health hazards in outdoor settings? Environ Sci Technol 2015; 49(17):10607-15.

8. Liu Y, Chen YY, Cao JY, Tao FB, Zhu XX, Yao CJ, et al. Oxidative stress, apoptosis, and cell cycle arrest are induced in primary fetal alveolar type Ⅱ epithelial cells exposed to fine particulate matter from cooking oil fumes. Environ Sci Pollut Res Int 2015; 22(13):9728-41. doi: 10.1007/s11356-015-4140-4.

9. Yin ZH, Cui ZG, Guan P, Li XL, Wu W, Ren YW, et al. Interaction between polymorphisms in pre-miRNA genes and cooking oil fume exposure on the risk of lung cancer in Chinese non-smoking female population. PLoS One 2015;10(6):e0128572. doi: 10.1371/journal.pone.0128572.

10. Ren YW, Yin ZH, Li K, Wan Y, Li XL, Wu W, et al. TGFbeta-1 and TGFBR2 polymorphisms, cooking oil fume exposure and risk of lung adenocarcinoma in Chinese nonsmoking females: a case control study. BMC Med Genet 2015;16:22. doi: 10.1186/s12881-015-0170-5.

11. Phukan RK, Saikia BJ, Borah PK, Zomawia E, Sekhon GS,Mahanta J. Role of household exposure, dietary habits and glutathione S-transferases M1, T1 polymorphisms in susceptibility to lung cancer among women in Mizoram India.Asian Pac J Cancer Prev 2014; 15(7):3253-60. doi: 10.7314/apjcp.2014.15.7.3253.

12. Wang XR, Chiu YL, Qiu H, Au JSK, Yu ITS. The roles of smoking and cooking emissions in lung cancer risk among Chinese women in Hong Kong. Ann Oncol 2009; 20(4):746-51. doi: 10.1093/annonc/mdn699.

13. Li MC, Yin ZH, Guan P, Li XL, Cui ZS, Zhang J, et al. XRCC1 polymorphisms, cooking oil fume and lung cancer in Chinese women nonsmokers. Lung Cancer 2008; 62(2):145-51. doi: 10.1016/j.lungcan.2008.03.002.

14. Hung HS, Wu WJ, Cheng YW, Wu TC, Chang KL, Lee H.Association of cooking oil fumes exposure with lung cancer: involvement of inhibitor of apoptosis proteins in cell survival and proliferationin vitro. Mutat Res 2007;628(2):107-16. doi: 10.1016/j.mrgentox.2006.12.005.

15. Yu ITS, Chiu YL, Au JSK, Wong TW, Tang JL. Dose-response relationship between cooking fumes exposures and lung cancer among Chinese nonsmoking women.Cancer Res 2006; 66(9):4961-7. doi: 10.1158/0008-5472.CAN-05-2932.

16. Metayer C, Wang ZY, Kleinerman RA, Wang LD, Brenner AV, Cui HX, et al. Cooking oil fumes and risk of lung cancer in women in rural Gansu, China. Lung Cancer 2002; 35(2):112-7. doi: 10.1016/s0169-5002(01)00412-3.

17. Wu SC, Yen GC. Effects of cooking oil fumes on the genotoxicity and oxidative stress in human lung carcinoma (A-549) cells. Toxicol In Vitro 2004; 18(5):571-80. doi:10.1016/j.tiv.2004.01.004.

18. Lee T, Gany F. Cooking oil fumes and lung cancer: a review of the literature in the context of the U.S. population. J Immigr Minor Health 2013; 15(3):646-52. doi: 10.1007/s10903-012-9651-1.

19. Mohammed MO, Song WW, Ma WL, Li WL, Khan AU, Ibrahim MA, et al. Potential toxicological and cardiopulmonary effects of PM 2.5 exposure and related mortality: findings of recent studies published during 2003-2013. Biomed Environ Sci 2016; 29(1):66-79. doi: 10.3967/bes2016.007.

20. Wu M, Che W, Zhang Z. Enhanced sensitivity to DNA damage induced by cooking oil fumes in human OGG1 deficient cells. Environ Mol Mutagen 2008; 49(4):265-75.doi: 10.1002/em.20381.

21. Mi HH. Optical emission spectroscopy in cooking exhaust from a wet scrubber/atmospheric plasma reactor. Aerosol Air Qual Res 2014; 10(6):1665-74. doi: 10.4209/aaqr.2014.01.0002.

22. Xue X, Liao WT, Chang HC, Chen SJ, Lin CC, Hsieh LT. The joint effect of hOGG1, APE1, and ADPRT polymorphisms and cooking oil fumes on the risk of lung adenocarcinoma in Chinese non-smoking females. PLoS One 2013; 8(8):e71157. doi: 10.1371/journal.pone.0071157.

23. Yin ZH, Su M, Li XL, Li MC, Ma R, He QC, et al. ERCC2,ERCC1 polymorphisms and haplotypes, cooking oil fume and lung adenocarcinoma risk in Chinese non-smoking females. J Exp Clin Cancer Res 2009; 28:153. doi: 10.1186/1756-9966-28-153.

24. Cooke MS, Evans MD, Dove R, Rozalski R, Gachowski D,Siomek A, et al. DNA repair is responsible for the presence of oxidatively damaged DNA lesions in urine. Mutat Res 2005; 574(1):58-66. doi: 10.1016/j.mrfmmm.2005.01.022.

25. Pan CH, Chan CC, Wu KY. Effects on Chinese restaurant workers of exposure to cooking oil fumes: a cautionary note on urinary 8-hydroxy-2'-deoxyguanosine. Cancer Epidemiol Biomarkers Prev 2008; 17(12):3351-7. doi:10.1158/1055-9965.EPI-08-0075.

26. Lewis BP, Shih L, Jones-Rhoades MW, Bartel DP, Burge CB.Prediction of mammalian microRNA targets. Cell 2003;115(7):787-98. doi: 10.1016/s0092-8674(03)01018-3.

27. Petermann E, Keil C, Oei SL. Roles of DNA ligase Ⅲ and XRCC1 in regulating the switch between short patch and long patch BER. DNA Repair (Amst) 2006; 5(5):544-55.doi: 10.1016/j.dnarep.2005.12.008.

28. Josyula S, Lin J, Xue XN, Rothman N, Lan Q, Rohan TE,et al. Household air pollution and cancers other than lung:a meta-analysis. Environ Health 2015; 14:24. doi: 10.1186/s12940-015-0001-3.

29. Cao J, Ding R, Wang Y, Chen DJ, Guo DM, Liang CM, et al.Toxic effect of cooking oil fumes in primary fetal pulmonary type Ⅱ-like epithelial cells. Environ Toxicol Pharmacol 2013; 36(2):320-31. doi: 10.1016/j.etap.2013. 04.011.

30. Che Z, Liu Y, Chen YY, Cao JY, Liang CM, Wang L, et al.The apoptotic pathways effect of fine particulate from cooking oil fumes in primary fetal alveolar type Ⅱ epithelial cells. Mutat Res Genet Toxicol Environ Mutagen 2014;761:35-43. doi: 10.1016/j.mrgentox.2014.01.004.

10.24920/J1001-9294.2017.026