MESLEK HASTALIKLARIYLA İLİŞKİLİ GENETİK POLİMORFİZMLERİN MOLEKÜLER MEKANİZMALARI

Meslek hastalıkları, iş yerinde fiziksel, kimyasal, biyolojik ve psikolojik etkenlerle karşılaşan çalışanın kişisel özelliklerine bağlı olarak gelişen geçici veya sürekli hastalıklardır. Tamamen önlenebilir hastalıklardan olan meslek hastalıkları, beslenme alışkanlığı, genetik varyasyonlar, sigara ve alkol kullanımı, obezite gibi bir çok faktöre bağlı olarak ortaya çıkmaktadır. Meslek hastalıklara karşı duyarlılıkta popülasyondaki kişisel farklılıkların belirlenmesini sağlayan hastalığa yatkınlık nedeni olan genetik polimorfizmlerin bir kısmı hastalık riskini arttırırken, bir kısmı da azaltabilmektedir. Bu derlemenin amacı; meslek hastalıklarına yatkınlıkla ilgili genetik polimorfizm profilleri kullanılarak genlerin ve polimorfizmlerin belirlenmesiyle hastalıklara yatkınlık taraması yapılmasının ve hastaların genotipine uygun bireysel tedavi seçeneklerinin geliştirilmesinin olası yararlarını araştırmaktır. Genel popülasyondaki yüksek prevalansları nedeniyle, çevresel risklere duyarlılığı belirleyen genetik polimorfizmler, işyerinde ortaya çıkan spesifik risklerin belirlenmesiyle mesleki hastalıkların tespitine büyük katkı sağlayabilirler. Korunma önlemleri yeterince alınmayan iş yerlerinde, genetik olarak yatkınlık taşıyan kişilerde, duyarlılaştırıcı özellik taşıyan etkenlerle yoğun ve uzun süreli temasta riskin artacağı açıktır. İşyerinde genetik duyarlılıkları araştıran çalışmalar, hastalığın etiyolojisinin, özellikle de çevreye duyarlı genlerin belirlenmesini; maruz kalma açısından hassas alt popülasyonların tanımlanmasını; genetik duyarlılığı göz önünde bulundurarak mesleki maruz kalma sınırlarının belirlenmesinde faydalı veriler sağlamaktadır. Genetik duyarlılık polimorfizmlerinin hastalık riskini belirlemede açık bir rolü olsa bile, çalışma ortamlarındaki geniş ölçekli genetik taramanın değeri, etik ve sosyal kaygılar nedeniyle sınırlı kalmaktadır. Bu nedenle, işyerlerinde büyük ölçekli genetik tarama yapılması şu anda önerilmemektedir.

Anahtar Kelimeler:

Genetik polimorfizm, meslek hastalıkları, gürültüye bağlı işitme kaybı, kurşun zehirlenmesi, pnömokonyoz

MOLECULAR MECHANISMS OF GENETIC POLYMORPHISMS RELATED TO OCCUPATIONAL DISEASES

Occupational diseases are transient or permanent and completely preventable diseases that occur due to many factors (feeding habits, genetic variations, obesity etc) that develop depending on the personal characteristics of the employees who encounter physical, chemical, biological and psychological factors at work. Some of the genetic polymorphisms may increase the risk of disease while others may reduce it. The aim of this review is to investigate the possible benefits of susceptibility screening for diseases by identifying genes and polymorphisms, using genetic polymorphism profiles related to occupational disease susceptibility, and developing individual treatment options appropriate to the genotype of the patients. Genetic polymorphisms that determine susceptibility to environmental risks can contribute greatly to the identification of occupational diseases by identifying specific risks in the workplace. It is evident that the risk of intense and prolonged contact with sensitizing agents will increase in genetically susceptible individuals. Studies investigating genetic susceptibilities in the workplace determine the etiology of the disease, environmentally sensitive genes and identify sensitive subpopulations; providing beneficial data for determining occupational exposure limits considering genetic sensitivity. The value of large-scale genetic screenings in work environments remains limited due to ethical and social concerns. Therefore, large-scale genetic screening in workplaces is not currently recommended.

Keywords:

Genetic polymorphism, occupational diseases, noise-induced hearing loss, lead poisoning, pneumoconiosis,

PDF

___

1. Çalışma ve Sosyal Güvenlik Bakanlığı İş Sağlığı ve Güvenliği Genel Müdürlüğü (İSGGM). Meslek Hastalıkları Rehberi. Ankara: Matsa Basımevi; 2011.
2. Güven R. Mesleki Hastalıkların Tanımı, Tarihçesi, Epidemiyolojisi. Özyardımcı N, editör. Mesleksel Hastalıklar Kitabı. Uludağ Üniversitesi Basımevi: Bursa; 2007. s. 3-61.
3. Davoodi S, Haghighi SK, Kalhori NRS, Hosseini SN, Mohammadzadeh Z, Safdari R. Occupational Disease Registries-Characteristics and Experiences. Acta Inform Med 2017;25(2):136-40.
4. T.C. Çalışma ve Sosyal Güvenlik Bakanlığı. Meslek Hastalıkları ve İş ile İlgili Hastalıklar Tanı Rehberi. 2018. s.490.
5. Machida S. List of occupational diseases (revised 2010). Identification and recognition of occupational diseases: Criteria for incorporating diseases in the ILO list of occupational diseases. Occupational Safety and Health Series. Programme of Safety and Health at Work and the Environment (SafeWork) (Genève 22, Switzerland). International Labour Office: 2010. Report No: MEULOD/2005/1-2-3.
6. Christiani DC, Mehta AJ, Yu CL. Genetic susceptibility to occupational exposures. Occup Environ Med 2008;65(6):430-6.
7. Khoury M, Beaty T, Cohen B. Fundamentals of genetic epidemiology. In: Morton EN, editor. Genetic epidemiology. New York: Oxford University Press; 1993. p. 389-90.
8. Zheng G, Tian L, Liang Y, Broberg K, Lei L, Guo W, et al. δ-Aminolevulinic acid dehydratase genotype predicts toxic effects of lead on workers’ peripheral nervous system. Neurotoxicology 2011;32(4):374-82.
9. Zhang H, Xu M, Zhao Q, Sun K, Gong W, Zhang Q, et al. Association between Polymorphism of Exportin-5 and Susceptibility to Lead Poisoning in a Chinese Population. Int J Environ Res Public Health 2017;14(1):36.
10. Lin C, Ni QZ, Rong XQ, Li BZ, Min ED, Shen BW, et al. Association between the HOTAIR Polymorphism and Susceptibility to Lead Poisoning in a Chinese Population. Biomed Environ Sci 2018;31(6):473-8.
11. Qian XR, Chen L, Liu JT, Zhu BL, Zhao QN, Ding EM, et al. Association between Polymorphisms of MALAT1 and Blood Lead Levels in Lead-exposed Workers. Biomed Environ Sci 2018;31(7):527-30.
12. Siha SM, Shaker AHD, Teleb SH, Rashed AL. Effects of delta- Aminolevulinic Acid Dehydratase Gene Polymorphism on Hematological Parameters and Kidney Function of Leadexposed Workers. Int J Occup Environ Med 2019:10(2):8993.
13. Songa X, Gongb W, Shenc H, Lia X, Dinge L, Hanb L, et al. Correlation between CAT polymorphism and susceptibility to DMAc-induced abnormal liver function: a case-control study of Chinese population. Biomarkers 2018;23(2):147-53.
14. Tong Z, Shen H, Dandan Y, Zhang F, Bai Y, Li Q, et al. Genetic Variations in the Promoter of the APE1 Gene Are Associated with DMF-Induced Abnormal Liver Function: A Case-Control Study in a Chinese Population. Int J Environ Res Public Health 2016;13(8):752.
15. Nomiyama T, Haufroid U, Buchet Pierre J, Miyauchi H, Tanaka S, Yamauchi T, et al. Insertion polymorphism of CYP2E1 and urinary N -methylformamide after N,N - dimethylformamide exposure in Japanese workers. Int Arch Occup Environ Health 2001;74(7):519-22.
16. Xue P, Gao L, Xiao S, Zhang G, Xiao M, Zhang Q, et al. Genetic Polymorphisms in XRCC1, CD3EAP, PPP1R13L, XPB, XPC, and XPF and the Risk of Chronic Benzene Poisoning in a Chinese Occupational Population. Plos One 2015;10(12): e0144458.
17. Nourozi AM, Neghab M, Bazzaz TJ, Nejat S, Mansoori Y, Shahtaheri JS. Association between polymorphism of GSTP1, GSTT1, GSTM1 and CYP2E1 genes and susceptibility to benzene-induced hematotoxicity. Archives of Toxicology 2018:92(6):1983-90.
18. Wu B, Ji X, Han R, Han L, Wang T, Yang J, et al. GITR promoter polymorphism contributes to risk of coal workers’ pneumoconiosis: a case-control study from China. Immunol Lett 2014;162(2):210-6.
19. Han R, Ji X, Wu B, Wang T, Han L, Yang J, et al. Polymorphisms in interleukin 17A gene and coal workers’ pneumoconiosis risk in a Chinese population. BMC Pulmonary Medicine 2015;15:79.
20. Ates I, Yucesoy B, Yucel A, Suzen SH, Karakas Y, Karakaya A. Possible effect of gene f] polymorphisms on the release of TNFα and IL1 cytokines in coal workers’ pneumoconiosis. Exp Toxicol Pathol 2011;63(1-2):175-9.
21. Ji X, Wang L, Wu B, Han R, Han L, Wang T, et al. Associations of MMP1, MMP2 and MMP3 Genes Polymorphism with Coal Workers’ Pneumoconiosis in Chinese Han Population. Int J Environ Res Public Health 2015;12(11):13901-12.
22. Ji X, Wu B, Han R, Yang J, Ayaaba E, Wang T, et al. The association of LAMB1 polymorphism and expression changes with the risk of coal workers’ pneumoconiosis. Environmental Toxicology 2017;32(9):2182-90.
23. Stanilova S, Miteva L, Prakova G. IL-12Bpro and GSTP1 polymorphisms in association with silicosis. Tissue Antigens 2008;71(2):169-74.
24. Stanilova S, Miteva L, Prakova G. Interleukin-12B-3’UTR polymorphism in association with IL-12p40 and IL-12p70 serum levels and silicosis severity. Int J Immunogenet 2007;34(3):193-9.
25. Weng S, Wang L, Rong Y, Liu Y, Wang X, Guan H, et al. Effects of the Interactions between Dust Exposure and Genetic Polymorphisms in Nalp3, Caspase-1, and IL-1β on the Risk of Silicosis: A Case-Control Study. Plos One 2015;10(10):e0140952.
26. Wang W, Yu Y, Wu S, Sang L, Wang X, Qiua A, et al. The rs2609255 polymorphism in the FAM13A gene is reproducibly associated with silicosis susceptibility in a Chinese population. Gene 2018;30(661):196-201.
27. Wang B, Ding E, Shen H, Wang J, Sun K, Chen S, et al. Association of TagSNP in lncRNA HOTAIR with susceptibility to noise-induced hearing loss in a Chinese population. Hearing Research 2017;347:41-6.
28. Abreu-Silva RS, Rincon D, Horimoto AR, Sguillar AP, Ricardo LA, Kimura L,et al. The search of a genetic basis for noiseinduced hearing loss (NIHL). Ann Hum Biol 2011;38(2):2108.
29. Guo H, Ding E, Sheng R, Cheng J, Cai W, Guo J, et al. Genetic variation in KCNQ4 gene is associated with susceptibility to noise induced hearing loss in a Chinese population. Environmental Toxicology and Pharmacology 2018;63:55-9.
30. Ding E, Liu J, Shen H, Gong W, Zhang H, Song H, et al. Notch polymorphisms associated with sensitivity of noise induced hearing loss among Chinese textile factory workers. BMC Medical Genetics 2018;19(1):168.
31. Xu X, Yang Q, Jiao J, He L, Yu S, Wang J, et al. Genetic Variation in POU4F3 and GRHL2 Associated with NoiseInduced Hearing Loss in Chinese Population: A CaseControl Study. Int J Environ Res Public Health 2016;13(6):561.
32. Braga MP, Maciel SM, Marchiori LL, Poli-Frederico RC. Association between interleukin-6 polymorphism in the -174 G/C region and hearing loss in the elderly with a history of occupational noise exposure. Braz J Otorhinolaryngol 2014;80(5):373-8.
33. Li X, Cao J, Wang J, Song H, Ji G, Dong Q, et al. PON2 and ATP2B2 gene polymorphisms with noise-induced hearing loss. J Thorac Dis 2016;8(3):430-8.
34. Guo H, Ding E, Bai Y, Zhang H, Shen H, Wang J, et al. Association of genetic variations in FOXO3 gene with susceptibility to noise induced hearing loss in a Chinese population. Plos One 2017;12(12):e0189186.
35. Shen H, Dou J, Han L, Bai Y, Li Q, Hong Z, et al. Genetic variation in APE1 gene promoter is associated with noiseinduced hearing loss in a Chinese population. Int Arch Occup Environ Health 2016;89(4):621-8.
36. Yang Q, Xu X, Jiao J, Zheng Y, He L, Yu S, et al. Genetic variation in EYA4 on the risk of noise-induced hearing loss in Chinese steelworks firm sample. Occup Environ Med 2016;73(12):823-8.
37. Bhatt I, Phillips S, Richter S, Tucker D, Lundgren K, Morehouse R, Henrich V. A polymorphism in human estrogen-related receptor beta (ESRRβ) predicts audiometric temporary threshold shift. Int J Audiol 2016;55(10):571-9.
38. Christiani DC, Sharp RR, Collman GW, Suk WA. Applying genomic technologies in environmental health research: challenges and opportunities. J Occup Environ Med 2001;43(6):526-33.
39. Vineis P, Christiani DC. Genetic testing for sale. Epidemiology 2004;15(1):3-5.
40. Khoury MJ. Will genetics revolutionize medicine? N Engl J Med 2000;343(20):1497-98.
41. Burke W. Genetic testing. N Engl J Med 2002;347(23):186775.
42. Vineis P, Schulte P, McMichael AJ. Misconceptions about the use of genetic tests in populations. Lancet 2001;357(9257):709-12.
43. Easton D, Farin F, Omiecinski C, et al. Genetic susceptibility. In: Rom W, editor. Environmental and occupational medicine. Philadelphia: Lippincott-Raven; 1998. p. 209-21.