Environmental Risk Factors for Liver Cancer and Nonalcoholic Fatty Liver Disease

Abstract

Purpose of Review

The objective of this review was to summarize recent epidemiologic research examining the associations between environmental exposures and liver cancer and nonalcoholic fatty liver disease (NAFLD).

Recent Findings

There were 28 liver cancer studies showing positive associations for exposures to aflatoxin, air pollution, polycyclic aromatic hydrocarbons, asbestos, chimney sweeping occupation, and paints; an inverse association for ultraviolet radiation; and null/inconsistent results for organic solvents, pesticides, perfluorooctanoic acid, nuclear radiation, iron foundry occupation, and brick kiln pollution. There were n = 5 NAFLD studies showing positive associations for heavy metals, methyl tertiary-butyl ether, and selenium; and no association with trihalomethanes.

Summary

Evidence suggests that particular environmental exposures may be associated with liver cancer and NAFLD. Future liver cancer studies should examine specific histological subtypes and assess historical environmental exposures. Future NAFLD research should examine incident, biopsy-confirmed cases, and the potential role of obesity and/or diabetes in studies of environmental factors and NAFLD.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.

    Tapper EB, Parikh ND. Mortality due to cirrhosis and liver cancer in the United States, 1999–2016: observational study. BMJ. 2018;362:k2817. https://doi.org/10.1136/bmj.k2817.

    PubMed  PubMed Central  Article  Google Scholar 

  2. 2.

    Ryerson AB, Eheman CR, Altekruse SF, Ward JW, Jemal A, Sherman RL, et al. Annual report to the nation on the status of cancer, 1975-2012, featuring the increasing incidence of liver cancer. Cancer. 2016;122(9):1312–37. https://doi.org/10.1002/cncr.29936.

    PubMed  PubMed Central  Article  Google Scholar 

  3. 3.

    Wong MC, Jiang JY, Goggins WB, Liang M, Fang Y, Fung FD, et al. International incidence and mortality trends of liver cancer: a global profile. Sci Rep. 2017;7:45846. https://doi.org/10.1038/srep45846.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  4. 4.

    Global Burden of Disease Liver Cancer C, Akinyemiju T, Abera S, Ahmed M, Alam N, Alemayohu MA, et al. The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the Global Burden of Disease Study 2015. JAMA Oncol. 2017;3(12):1683–91. https://doi.org/10.1001/jamaoncol.2017.3055.

    Article  Google Scholar 

  5. 5.

    Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424. https://doi.org/10.3322/caac.21492.

    PubMed  Article  Google Scholar 

  6. 6.

    Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Niksic M, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet. 2018;391(10125):1023–75. https://doi.org/10.1016/S0140-6736(17)33326-3.

    PubMed  Article  PubMed Central  Google Scholar 

  7. 7.

    El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132(7):2557–76. https://doi.org/10.1053/j.gastro.2007.04.061.

    PubMed  CAS  Article  Google Scholar 

  8. 8.

    Carr B, editor. Hepatocellular carcinoma: diagnosis and treatment. Third ed. Cham: Springer International Publishing; 2016.

  9. 9.

    McGlynn KA, London WT. The global epidemiology of hepatocellular carcinoma: present and future. Clin Liver Dis. 2011;15(2):223–43, vii-x. https://doi.org/10.1016/j.cld.2011.03.006.

    PubMed  PubMed Central  Article  Google Scholar 

  10. 10.

    Smith JW, Kroker-Lobos MF, Lazo M, Rivera-Andrade A, Egner PA, Wedemeyer H, et al. Aflatoxin and viral hepatitis exposures in Guatemala: molecular biomarkers reveal a unique profile of risk factors in a region of high liver cancer incidence. PLoS One. 2017;12(12):e0189255. https://doi.org/10.1371/journal.pone.0189255.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  11. 11.

    Makarova-Rusher OV, Altekruse SF, McNeel TS, Ulahannan S, Duffy AG, Graubard BI, et al. Population attributable fractions of risk factors for hepatocellular carcinoma in the United States. Cancer. 2016;122(11):1757–65. https://doi.org/10.1002/cncr.29971.

    PubMed  PubMed Central  Article  Google Scholar 

  12. 12.

    Bush H, Golabi P, Younossi ZM. Pediatric non-alcoholic fatty liver disease. Children. 2017;4(6). https://doi.org/10.3390/children4060048.

  13. 13.

    Loomba R, Sanyal AJ. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol. 2013;10(11):686–90. https://doi.org/10.1038/nrgastro.2013.171.

    PubMed  CAS  Article  Google Scholar 

  14. 14.

    Welsh JA, Karpen S, Vos MB. Increasing prevalence of nonalcoholic fatty liver disease among United States adolescents, 1988–1994 to 2007–2010. J Pediatr. 2013;162(3):496–500 e1. https://doi.org/10.1016/j.jpeds.2012.08.043.

    PubMed  Article  Google Scholar 

  15. 15.

    Kanwal F, Kramer JR, Mapakshi S, Natarajan Y, Chayanupatkul M, Richardson PA, et al. Risk of hepatocellular cancer in patients with non-alcoholic fatty liver disease. Gastroenterology. 2018;155:1828–1837.e2. https://doi.org/10.1053/j.gastro.2018.08.024.

    PubMed  Article  Google Scholar 

  16. 16.

    Younossi Z, Anstee QM, Marietti M, Hardy T, Henry L, Eslam M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2018;15(1):11–20. https://doi.org/10.1038/nrgastro.2017.109.

    PubMed  Article  Google Scholar 

  17. 17.

    Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73–84. https://doi.org/10.1002/hep.28431.

    PubMed  Article  Google Scholar 

  18. 18.

    Ray K. NAFLD-the next global epidemic. Nat Rev Gastroenterol Hepatol. 2013;10(11):621. https://doi.org/10.1038/nrgastro.2013.197.

    PubMed  Article  Google Scholar 

  19. 19.

    VanWagner LB, Armstrong MJ. Lean NAFLD: A not so benign condition? Hepatol Commun. 2018;2(1):5–8. https://doi.org/10.1002/hep4.1143.

    PubMed  PubMed Central  Article  Google Scholar 

  20. 20.

    Ahmed MH, Husain NE, Almobarak AO. Nonalcoholic fatty liver disease and risk of diabetes and cardiovascular disease: what is important for primary care physicians? J Fam Med Prim Care. 2015;4(1):45–52. https://doi.org/10.4103/2249-4863.152252.

    CAS  Article  Google Scholar 

  21. 21.

    Goh GB, Pagadala MR, Dasarathy J, Unalp-Arida A, Sargent R, Hawkins C, et al. Clinical spectrum of non-alcoholic fatty liver disease in diabetic and non-diabetic patients. BBA Clin. 2015;3:141–5. https://doi.org/10.1016/j.bbacli.2014.09.001.

    PubMed  Article  Google Scholar 

  22. 22.

    Kim D, Kim WR. Nonobese fatty liver disease. Clin Gastroenterol Hepatol. 2017;15(4):474–85. https://doi.org/10.1016/j.cgh.2016.08.028.

    PubMed  CAS  Article  Google Scholar 

  23. 23.

    Sturgill MG, Lambert GH. Xenobiotic-induced hepatotoxicity: mechanisms of liver injury and methods of monitoring hepatic function. Clin Chem. 1997;43(8 Pt 2):1512–26.

    PubMed  CAS  Google Scholar 

  24. 24.

    Ledda C, Loreto C, Zammit C, Marconi A, Fago L, Matera S, et al. Noninfective occupational risk factors for hepatocellular carcinoma: a review (review). Mol Med Rep. 2017;15(2):511–33. https://doi.org/10.3892/mmr.2016.6046.

    PubMed  CAS  Article  Google Scholar 

  25. 25.

    Yorita Christensen KL, Carrico CK, Sanyal AJ, Gennings C. Multiple classes of environmental chemicals are associated with liver disease: NHANES 2003-2004. Int J Hyg Environ Health. 2013;216(6):703–9. https://doi.org/10.1016/j.ijheh.2013.01.005.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  26. 26.

    Bishayee A. The role of inflammation and liver cancer. Adv Exp Med Biol. 2014;816:401–35. https://doi.org/10.1007/978-3-0348-0837-8_16.

    PubMed  CAS  Article  Google Scholar 

  27. 27.

    Wang Z, Li Z, Ye Y, Xie L, Li W. Oxidative stress and liver cancer: etiology and therapeutic targets. Oxidative Med Cell Longev. 2016;2016:7891574–10. https://doi.org/10.1155/2016/7891574.

    CAS  Article  Google Scholar 

  28. 28.

    Trevino LS, Katz TA. Endocrine disruptors and developmental origins of nonalcoholic fatty liver disease. Endocrinology. 2018;159(1):20–31. https://doi.org/10.1210/en.2017-00887.

    PubMed  Article  Google Scholar 

  29. 29.

    Deierlein AL, Rock S, Park S. Persistent endocrine-disrupting chemicals and fatty liver disease. Cur Environ Health Rep. 2017;4(4):439–49. https://doi.org/10.1007/s40572-017-0166-8.

    CAS  Article  Google Scholar 

  30. 30.

    Foulds CE, Trevino LS, York B, Walker CL. Endocrine-disrupting chemicals and fatty liver disease. Nat Rev Endocrinol. 2017;13(8):445–57. https://doi.org/10.1038/nrendo.2017.42.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  31. 31.

    Wahlang B, Beier JI, Clair HB, Bellis-Jones HJ, Falkner KC, McClain CJ, et al. Toxicant-associated steatohepatitis. Toxicol Pathol. 2013;41(2):343–60. https://doi.org/10.1177/0192623312468517.

    PubMed  CAS  Article  Google Scholar 

  32. 32.

    Al-Eryani L, Wahlang B, Falkner KC, Guardiola JJ, Clair HB, Prough RA, et al. Identification of environmental chemicals associated with the development of toxicant-associated fatty liver disease in rodents. Toxicol Pathol. 2015;43(4):482–97. https://doi.org/10.1177/0192623314549960.

    PubMed  CAS  Article  Google Scholar 

  33. 33.

    •• Lin YC, Lian IB, Kor CT, Chang CC, Su PY, Chang WT, et al. Association between soil heavy metals and fatty liver disease in men in Taiwan: a cross sectional study. BMJ Open. 2017;7(1):e014215. https://doi.org/10.1136/bmjopen-2016-014215. In a cross-sectional study in Taiwan, residential soil heavy metals exposure (arsenic, cadmium, chromium, copper, lead, mercury, nickel, zinc) was positively associated with NAFLD among males and among lean individuals with BMI < 24 kg/m 2 ; the potential environmental etiology of lean NAFLD should be investigated.

    PubMed  PubMed Central  Article  Google Scholar 

  34. 34.

    Do A, Lim JK. Epidemiology of nonalcoholic fatty liver disease: a primer. Clin Liver Dis. 2016;7(5):106–8.

    Article  Google Scholar 

  35. 35.

    Lazo M, Hernaez R, Eberhardt MS, Bonekamp S, Kamel I, Guallar E, et al. Prevalence of nonalcoholic fatty liver disease in the United States: the Third National Health and Nutrition Examination Survey, 1988–1994. Am J Epidemiol. 2013;178(1):38–45. https://doi.org/10.1093/aje/kws448.

    PubMed  PubMed Central  Article  Google Scholar 

  36. 36.

    Rinella M, Charlton M. The globalization of nonalcoholic fatty liver disease: prevalence and impact on world health. Hepatology. 2016;64(1):19–22. https://doi.org/10.1002/hep.28524.

    PubMed  Article  Google Scholar 

  37. 37.

    Baker DB, Nieuwenhuijsen MJ, editors. Environmental epidemiology: study methods and application. Oxford: Oxford University Press; 2008.

    Google Scholar 

  38. 38.

    • Long XD, Zhao D, Wang C, Huang XY, Yao JG, Ma Y, et al. Genetic polymorphisms in DNA repair genes XRCC4 and XRCC5 and aflatoxin B1-related hepatocellular carcinoma. Epidemiology. 2013;24(5):671–81. https://doi.org/10.1097/EDE.0b013e31829d2744. This retrospective case-control study in China showed evidence of a GxE interaction between serum aflatoxin and variants for the XRCC4 DNA repair gene, providing new perspectives on biological mechanisms and genetic susceptibility.

    PubMed  Article  Google Scholar 

  39. 39.

    •• Yao JG, Huang XY, Long XD. Interaction of DNA repair gene polymorphisms and aflatoxin B1 in the risk of hepatocellular carcinoma. Int J Clin Exp Pathol. 2014;7(9):6231–44. This retrospective case-control study in China investigated GxE interactions between serum aflatoxin exposure and genetic polymorphisms in DNA repair genes (e.g., XRCC4 ), providing new insights into aflatoxin (a known risk factor for HCC) through highlighting potential biological mechanisms for HCC development and identifying individuals at high risk for aflatoxin-induced HCC.

    PubMed  PubMed Central  Google Scholar 

  40. 40.

    Chu YJ, Yang HI, Wu HC, Liu J, Wang LY, Lu SN, et al. Aflatoxin B1 exposure increases the risk of cirrhosis and hepatocellular carcinoma in chronic hepatitis B virus carriers. Int J Cancer. 2017;141(4):711–20. https://doi.org/10.1002/ijc.30782.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  41. 41.

    Lai H, Mo X, Yang Y, He K, Xiao J, Liu C, et al. Association between aflatoxin B1 occupational airway exposure and risk of hepatocellular carcinoma: a case-control study. Tumour Biol. 2014;35(10):9577–84. https://doi.org/10.1007/s13277-014-2231-3.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  42. 42.

    • Pan WC, Wu CD, Chen MJ, Huang YT, Chen CJ, Su HJ, et al. Fine particle pollution, alanine transaminase, and liver cancer: a Taiwanese Prospective Cohort Study (REVEAL-HBV). J Natl Cancer Inst. 2016;108(3). https://doi.org/10.1093/jnci/djv341. In the REVEAL-HBV prospective cohort study, there was a statistically significant positive association between residential PM 2.5 exposure and HCC risk on the Taiwan Penghu Islands after adjustment for risk factors including HBV and HCV, although there was a temporal mismatch in the exposure assessment.

  43. 43.

    •• Pedersen M, Andersen ZJ, Stafoggia M, Weinmayr G, Galassi C, Sorensen M, et al. Ambient air pollution and primary liver cancer incidence in four European cohorts within the ESCAPE project. Environ Res. 2017;154:226–33. https://doi.org/10.1016/j.envres.2017.01.006. In the ESCAPE prospective cohort study in Europe, there were suggestive positive associations between geospatial-based residential exposures to air pollutants including NO 2 , NO x , PM 10 , PM 2.5 , and PM 2.5–10 and liver cancer risk. Exposure assessment was based on high-resolution land use regression models, although there was a temporal mismatch in exposures estimated after cases were diagnosed. However, these results are consistent with evidence showing that smoking, blood B[ a ]P (PAH found in tobacco smoke and air pollution), and occupational exposure among chimney sweepers (e.g., soot that contains PAHs) increase liver cancer risk.

    PubMed  CAS  Article  Google Scholar 

  44. 44.

    Niu J, Lin Y, Guo Z, Niu M, Su C. The epidemiological investigation on the risk factors of hepatocellular carcinoma: a case-control study in Southeast China. Medicine (Baltimore). 2016;95(6):e2758. https://doi.org/10.1097/MD.0000000000002758.

    Article  Google Scholar 

  45. 45.

    • Su Y, Zhao B, Guo F, Bin Z, Yang Y, Liu S, et al. Interaction of benzo[a]pyrene with other risk factors in hepatocellular carcinoma: a case-control study in Xiamen, China. Ann Epidemiol. 2014;24(2):98–103. https://doi.org/10.1016/j.annepidem.2013.10.019. This retrospective case-control study in China provided further evidence that B[ a ]P in blood is associated with increased HCC risk.

    PubMed  Article  Google Scholar 

  46. 46.

    • Tian M, Zhao B, Zhang J, Martin FL, Huang Q, Liu L, et al. Association of environmental benzo[a]pyrene exposure and DNA methylation alterations in hepatocellular carcinoma: a Chinese case-control study. Sci Total Environ. 2016;541:1243–52. https://doi.org/10.1016/j.scitotenv.2015.10.003. This retrospective case-control study in China investigated B[ a ]P exposure and epigenetics, showing higher levels GSTP (detoxification gene) hypermethylation among HCC cases compared to controls, and evidence of an interaction between GSTP gene methylation and serum BPDE-albumin adducts on HCC risk, although the determination of epigenetic alterations as a result of B[ a ]P vs. HCC is unclear. B[ a ]P is a PAH and IARC Group 1 human carcinogen found in air pollution and tobacco smoke.

  47. 47.

    Hogstedt C, Jansson C, Hugosson M, Tinnerberg H, Gustavsson P. Cancer incidence in a cohort of Swedish chimney sweeps, 1958-2006. Am J Public Health. 2013;103(9):1708–14. https://doi.org/10.2105/AJPH.2012.300860.

    PubMed  PubMed Central  Article  Google Scholar 

  48. 48.

    Boulanger M, Morlais F, Bouvier V, Galateau-Salle F, Guittet L, Marquignon MF, et al. Digestive cancers and occupational asbestos exposure: incidence study in a cohort of asbestos plant workers. Occup Environ Med. 2015;72(11):792–7. https://doi.org/10.1136/oemed-2015-102871.

    PubMed  Article  Google Scholar 

  49. 49.

    Wu WT, Lin YJ, Li CY, Tsai PJ, Yang CY, Liou SH, et al. Cancer attributable to Asbestos exposure in shipbreaking workers: a matched-cohort study. PLoS One. 2015;10(7):e0133128. https://doi.org/10.1371/journal.pone.0133128.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  50. 50.

    Wu WT, Lin YJ, Shiue HS, Li CY, Tsai PJ, Yang CY, et al. Cancer incidence of Taiwanese shipbreaking workers who have been potentially exposed to asbestos. Environ Res. 2014;132:370–8. https://doi.org/10.1016/j.envres.2014.04.026.

    PubMed  CAS  Article  Google Scholar 

  51. 51.

    Hansen J, Sallmen M, Selden AI, Anttila A, Pukkala E, Andersson K, et al. Risk of cancer among workers exposed to trichloroethylene: analysis of three Nordic cohort studies. J Natl Cancer Inst. 2013;105(12):869–77. https://doi.org/10.1093/jnci/djt107.

    PubMed  Article  Google Scholar 

  52. 52.

    Vlaanderen J, Straif K, Pukkala E, Kauppinen T, Kyyronen P, Martinsen JI, et al. Occupational exposure to trichloroethylene and perchloroethylene and the risk of lymphoma, liver, and kidney cancer in four Nordic countries. Occup Environ Med. 2013;70(6):393–401. https://doi.org/10.1136/oemed-2012-101188.

    PubMed  Article  Google Scholar 

  53. 53.

    Press DJ, McKinley M, Deapen D, Clarke CA, Gomez SL. Residential cancer cluster investigation nearby a superfund study area with trichloroethylene contamination. Cancer Causes Control. 2016;27(5):607–13. https://doi.org/10.1007/s10552-016-0734-5.

    PubMed  PubMed Central  Article  Google Scholar 

  54. 54.

    •• Yi SW, Ohrr H. Agent Orange exposure and cancer incidence in Korean Vietnam veterans: a prospective cohort study. Cancer. 2014;120(23):3699–706. https://doi.org/10.1002/cncr.28961. This prospective cohort study in the Korean Veterans Health Study showed that geospatial-based occupational Agent Orange exposure was associated with increased risk for liver cancer, adding to existing epidemiologic studies showing that DDT, another organochlorine compound, is associated with liver cancer risk.

    PubMed  Article  Google Scholar 

  55. 55.

    Yi SW, Ohrr H, Hong JS, Yi JJ. Agent Orange exposure and prevalence of self-reported diseases in Korean Vietnam veterans. J Prev Med Public Health. 2013;46(5):213–25. https://doi.org/10.3961/jpmph.2013.46.5.213.

    PubMed  PubMed Central  Article  Google Scholar 

  56. 56.

    Silver SR, Bertke SJ, Hines CJ, Alavanja MC, Hoppin JA, Lubin JH, et al. Cancer incidence and metolachlor use in the agricultural health study: an update. Int J Cancer. 2015;137(11):2630–43. https://doi.org/10.1002/ijc.29621.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  57. 57.

    VoPham T, Brooks MM, Yuan JM, Talbott EO, Ruddell D, Hart JE, et al. Pesticide exposure and hepatocellular carcinoma risk: A case-control study using a geographic information system (GIS) to link SEER-Medicare and California pesticide data. Environ Res. 2015;143(Pt A):68–82. https://doi.org/10.1016/j.envres.2015.09.027.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  58. 58.

    Kachuri L, Harris MA, MacLeod JS, Tjepkema M, Peters PA, Demers PA. Cancer risks in a population-based study of 70,570 agricultural workers: results from the Canadian census health and environment cohort (CanCHEC). BMC Cancer. 2017;17(1):343. https://doi.org/10.1186/s12885-017-3346-x.

    PubMed  PubMed Central  Article  Google Scholar 

  59. 59.

    Vieira VM, Hoffman K, Shin HM, Weinberg JM, Webster TF, Fletcher T. Perfluorooctanoic acid exposure and cancer outcomes in a contaminated community: a geographic analysis. Environ Health Perspect. 2013;121(3):318–23. https://doi.org/10.1289/ehp.1205829.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  60. 60.

    Barry V, Winquist A, Steenland K. Perfluorooctanoic acid (PFOA) exposures and incident cancers among adults living near a chemical plant. Environ Health Perspect. 2013;121(11–12):1313–8. https://doi.org/10.1289/ehp.1306615.

    PubMed  PubMed Central  Article  Google Scholar 

  61. 61.

    Westberg H, Andersson L, Bryngelsson IL, Ngo Y, Ohlson CG. Cancer morbidity and quartz exposure in Swedish iron foundries. Int Arch Occup Environ Health. 2013;86(5):499–507. https://doi.org/10.1007/s00420-012-0782-4.

    PubMed  CAS  Article  Google Scholar 

  62. 62.

    Labutina EV, Kuznetsova IS, Hunter N, Harrison J, Koshurnikova NA. Radiation risk of malignant neoplasms in organs of main deposition for plutonium in the cohort of Mayak workers with regard to histological types. Health Phys. 2013;105(2):165–76. https://doi.org/10.1097/HP.0b013e31828f57df.

    PubMed  CAS  Article  Google Scholar 

  63. 63.

    VoPham T, Bertrand KA, Yuan JM, Tamimi RM, Hart JE, Laden F. Ambient ultraviolet radiation exposure and hepatocellular carcinoma incidence in the United States. Environ Health. 2017;16(1):89. https://doi.org/10.1186/s12940-017-0299-0.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  64. 64.

    Pasetto R, Ranzi A, De Togni A, Ferretti S, Pasetti P, Angelini P, et al. Cohort study of residents of a district with soil and groundwater industrial waste contamination. Ann Ist Super Sanita. 2013;49(4):354–7. https://doi.org/10.4415/ANN_13_04_06.

    PubMed  Article  Google Scholar 

  65. 65.

    •• Janitz AE, Ramachandran G, Tomlinson GE, Krailo M, Richardson M, Spector L. Maternal and paternal occupational exposures and hepatoblastoma: results from the HOPE study through the Children’s Oncology Group. J Expo Sci Environ Epidemiol. 2017;27(4):359–64. https://doi.org/10.1038/jes.2017.1. A retrospective case-control study in the USA showed that self-reported paternal exposure to paints was associated with increased risk for hepatoblastoma, a rare pediatric liver tumor for which few modifiable risk factors are known.

    PubMed  PubMed Central  Article  Google Scholar 

  66. 66.

    Ross RK, Yuan JM, Yu MC, Wogan GN, Qian GS, Tu JT, et al. Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma. Lancet. 1992;339(8799):943–6.

    PubMed  CAS  Article  Google Scholar 

  67. 67.

    Davis GL, Dempster J, Meler JD, Orr DW, Walberg MW, Brown B, et al. Hepatocellular carcinoma: management of an increasingly common problem. PRO. 2008;21(3):266–80.

    Google Scholar 

  68. 68.

    International Agency for Research on Cancer. Outdoor Air Pollution. IARC Monographs on the evaluation of carcinogenic risks to humans. Geneva: WHO Press; 2016.

    Google Scholar 

  69. 69.

    Kim JW, Park S, Lim CW, Lee K, Kim B. The role of air pollutants in initiating liver disease. Toxicol Res. 2014;30(2):65–70.

    PubMed  PubMed Central  Article  Google Scholar 

  70. 70.

    Bostrom CE, Gerde P, Hanberg A, Jernstrom B, Johansson C, Kyrklund T, et al. Cancer risk assessment, indicators, and guidelines for polycyclic aromatic hydrocarbons in the ambient air. Environ Health Perspect. 2002;110(Suppl 3):451–88. https://doi.org/10.1289/ehp.110-1241197.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  71. 71.

    IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Some non-heterocyclic polycyclic aromatic hydrocarbons and some related exposures. IARC Monogr Eval Carcinog Risks Hum. 2010;92:1–853.

    PubMed Central  Google Scholar 

  72. 72.

    IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Chemical agents and related occupations. IARC Monogr Eval Carcinog Risks Hum. 2012;100(Pt F):9–562.

    PubMed Central  Google Scholar 

  73. 73.

    Baccarelli A, Bollati V. Epigenetics and environmental chemicals. Curr Opin Pediatr. 2009;21(2):243–51.

    PubMed  PubMed Central  Article  Google Scholar 

  74. 74.

    Klutstein M, Nejman D, Greenfield R, Cedar H. DNA methylation in cancer and aging. Cancer Res. 2016;76(12):3446–50. https://doi.org/10.1158/0008-5472.CAN-15-3278.

    PubMed  CAS  Article  Google Scholar 

  75. 75.

    IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Arsenic, metals, fibres, and dusts. IARC Monogr Eval Carcinog Risks Hum. 2012;100(Pt C):11–465.

    PubMed Central  Google Scholar 

  76. 76.

    IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Trichloroethylene, tetrachloroethylene, and some other chlorinated agents. IARC Monogr Eval Carcinog Risks Hum. 2014;106:1–512.

    PubMed Central  Google Scholar 

  77. 77.

    VoPham T, Bertrand KA, Hart JE, Laden F, Brooks MM, Yuan JM, et al. Pesticide exposure and liver cancer: a review. Cancer Causes Control. 2017;28(3):177–90. https://doi.org/10.1007/s10552-017-0854-6.

    PubMed  PubMed Central  Article  Google Scholar 

  78. 78.

    IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. DDT, Lindane, and 2,4-D. IARC monographs on the evaluation of carcinogenic risks to humans. Lyon: International Agency for Research on Cancer. 2018.

  79. 79.

    Steenland K, Fletcher T, Savitz DA. Epidemiologic evidence on the health effects of perfluorooctanoic acid (PFOA). Environ Health Perspect. 2010;118(8):1100–8. https://doi.org/10.1289/ehp.0901827.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  80. 80.

    IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Some chemicals used as solvents and in polymer manufacture. Lyon: International Agency for Research on Cancer. 2017.

  81. 81.

    Fukuhara T, Sharp GB, Mizuno T, Itakura H, Yamamoto M, Tokunaga M, et al. Liver cancer in atomic-bomb survivors: histological characteristics and relationships to radiation and hepatitis B and C viruses. J Radiat Res. 2001;42(2):117–30.

    PubMed  CAS  Article  Google Scholar 

  82. 82.

    • Hyder O, Chung M, Cosgrove D, Herman JM, Li Z, Firoozmand A, et al. Cadmium exposure and liver disease among US adults. J Gastrointest Surg. 2013;17(7):1265–73. https://doi.org/10.1007/s11605-013-2210-9. In a cross-sectional study in the USA, urinary cadmium levels (a heavy metal) was associated with NAFLD among males, representing additional evidence in a different study population showing a potential link between heavy metals exposure and NAFLD.

    PubMed  PubMed Central  Article  Google Scholar 

  83. 83.

    Burch JB, Everson TM, Seth RK, Wirth MD, Chatterjee S. Trihalomethane exposure and biomonitoring for the liver injury indicator, alanine aminotransferase, in the United States population (NHANES 1999–2006). Sci Total Environ. 2015;521–522:226–34. https://doi.org/10.1016/j.scitotenv.2015.03.050.

    PubMed  CAS  Article  Google Scholar 

  84. 84.

    Yang J, Wei Q, Peng X, Peng X, Yuan J, Hu D. Relationship between methyl tertiary butyl ether exposure and non-alcoholic fatty liver disease: a cross-sectional study among petrol station attendants in southern China. Int J Environ Res Public Health. 2016;13(10). https://doi.org/10.3390/ijerph13100946.

  85. 85.

    Yang Z, Yan C, Liu G, Niu Y, Zhang W, Lu S, et al. Plasma selenium levels and nonalcoholic fatty liver disease in Chinese adults: a cross-sectional analysis. Sci Rep. 2016;6:37288. https://doi.org/10.1038/srep37288.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  86. 86.

    Tchounwou PB, Yedjou CG, Patlolla AK, Sutton DJ. Heavy metal toxicity and the environment. EXS. 2012;101:133–64. https://doi.org/10.1007/978-3-7643-8340-4_6.

    PubMed  PubMed Central  Article  Google Scholar 

  87. 87.

    Dunn EC, Uddin M, Subramanian SV, Smoller JW, Galea S, Koenen KC. Research review: gene-environment interaction research in youth depression - a systematic review with recommendations for future research. J Child Psychol Psychiatry. 2011;52(12):1223–38. https://doi.org/10.1111/j.1469-7610.2011.02466.x.

    PubMed  PubMed Central  Article  Google Scholar 

  88. 88.

    Lee YC, Cohet C, Yang YC, Stayner L, Hashibe M, Straif K. Meta-analysis of epidemiologic studies on cigarette smoking and liver cancer. Int J Epidemiol. 2009;38(6):1497–511. https://doi.org/10.1093/ije/dyp280.

    PubMed  Article  Google Scholar 

  89. 89.

    IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Outdoor air pollution. IARC Monogr Eval Carcinog Risks Hum. 2016;109:9–444.

    Google Scholar 

  90. 90.

    Bowe B, Xie Y, Li T, Yan Y, Xian H, Al-Aly Z. The 2016 global and national burden of diabetes mellitus attributable to PM2.5 air pollution. Lancet Planet Health. 2018;2(7):e301–e12. https://doi.org/10.1016/S2542-5196(18)30140-2.

    PubMed  Article  Google Scholar 

  91. 91.

    Simon TG, King LY, Chong DQ, Nguyen LH, Ma Y, VoPham T, et al. Diabetes, metabolic comorbidities, and risk of hepatocellular carcinoma: results from two prospective cohort studies. Hepatology. 2018;67(5):1797–806. https://doi.org/10.1002/hep.29660.

    PubMed  CAS  Article  PubMed Central  Google Scholar 

  92. 92.

    Fedirko V, Duarte-Salles T, Bamia C, Trichopoulou A, Aleksandrova K, Trichopoulos D, et al. Prediagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations: a nested case-control study. Hepatology. 2014;60(4):1222–30. https://doi.org/10.1002/hep.27079.

    PubMed  CAS  Article  Google Scholar 

  93. 93.

    VoPham T, Weaver MD, Vetter C, Hart JE, Tamimi RM, Laden F, et al. Circadian misalignment and hepatocellular carcinoma incidence in the United States. Cancer Epidemiol Biomark Prev. 2018;27(7):719–27. https://doi.org/10.1158/1055-9965.EPI-17-1052.

    Article  Google Scholar 

  94. 94.

    La Merrill M, Emond C, Kim MJ, Antignac JP, Le Bizec B, Clement K, et al. Toxicological function of adipose tissue: focus on persistent organic pollutants. Environ Health Perspect. 2013;121(2):162–9. https://doi.org/10.1289/ehp.1205485.

    PubMed  CAS  Article  Google Scholar 

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Acknowledgments

The author would like to thank Isabel Holland for providing assistance in conducting the literature search.

Funding

This work was supported by the National Institutes of Health (NIH) National Cancer Institute (NCI) Training Program in Cancer Epidemiology (T32 CA009001).

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Correspondence to Trang VoPham.

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VoPham, T. Environmental Risk Factors for Liver Cancer and Nonalcoholic Fatty Liver Disease. Curr Epidemiol Rep 6, 50–66 (2019). https://doi.org/10.1007/s40471-019-0183-2

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Keywords

  • Liver cancer
  • Nonalcoholic fatty liver disease
  • Environmental exposures
  • Epidemiology
  • Risk factors