Pesticide Exposure and Head and Neck Cancers: A Case-Control Study in an Agricultural Region

Document Type: Original

Authors

1 Department of Otorhinolaryngology, Kerman University of Medical Sciences, Kerman, Iran.

2 Plant Protection Research Department, Yazd Agricultural and Natural Resources Research and Education Center, AREEO, Yazd, Iran.

3 Department of Plant Protection, University of Tabriz, Tabriz, Iran.

4 Neurology Research Center, Kerman University of Medical Sciences, Kerman, Iran.

Abstract

Introduction:
Causes of head and neck cancers (HNCs) are multifactorial, and few studies have investigated the association between chemical exposure and HNCs. The objective of this study was to investigate associations between HNCs, agricultural occupations, and pesticide exposure. The potential for the accumulation of pesticides in the adipose tissue of patients was also investigated.
 
Materials and Methods:
A structured questionnaire was used to collect information on demographics, occupation, and exposure to pesticides in a hospital-based case-control study. Pesticide residue in the adipose tissue of the neck in both cases and controls was also monitored via gas chromatography–mass spectroscopy.
 
Results:
Thirty-one HNC cases were included in this study as well as 32 gender-, age-, and smoking-matched controls. An agricultural occupation was associated with HNC (odds ratio [OR], 3.26; 95% confidence interval [CI], 1.13–9.43) after controlling for age, sex, and smoking. Pesticide exposure was associated with total HNC cases (OR, 7.45; 95% CI, 1.78–3.07) and larynx cancer (OR, 9.33; 95% CI, 1.65–52.68). A dose-response pattern was observed for HNC cases (P=0.06) and larynx cancer (P=0.01). In tracing the pesticide residue, five chlorinated pesticides, namely dichlorodiphenyltrichloroethane (DDT), dichlorodipheny-ldichloroethane (DDD), dichlorodiphenyldichloroethylene (DDE), dieldrin, and lindane, were identified in the adipose tissue. Chlorinated pesticide detection was significantly associated with HNC (OR, 3.91; 95% CI 0.9–0.16.9).
 
Conclusion:
HNCs were found to be associated with pesticide exposure after controlling for confounders. A high education level was identified as a modifying factor decreasing the risk of HNCs. Further studies with larger number of subjects are recommended to assess these relationships in greater detail.

Keywords

Main Subjects


1. Keyghobadi N, Rafiemanesh H, Mohammadian-Hafshejani A, et al. Epidemiology and trend of cancers in the province of Kerman: southeast of Iran. Asian Pac J Cancer Prev. 2015; 16:1409–13.

2. Döbróssy L. Epidemiology of head and neck cancer: magnitude of the problem. Cancer Metastasis Rev. 2005; 24:9–17.

3. Braakhuis BJ, Leemans CR, Visser O. Incidence and survival trends of head and neck squamous cell carcinoma in the Netherlands between 1989 and 2011. Oral Oncol. 2014; 50:670–75.

4. Olshan AF (ed). Epidemiology, pathogenesis, and prevention of Head and Neck Cancer. New York: Springer; 2010.

5. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136: E 359-86.

6. Casás-Selves M, DeGregori J. How cancer shapes evolution, and how evolution shapes cancer. Evolution. 2011; 4: 624–34.

7. Maier H, Weidauer H, Zoller J, et al. Effect of chronic alcohol consumption on the morphology of the oral mucosa. Alcohol CIin Exp Res. 1994;18: 387–9.

8. Dich J, Zahm SH, Hanberg A, Adami H-O. 1997. Pesticides and cancer. Cancer Causes Control. 1997;8: 420–43.

9. Weichenthal S, Moase C, Chan P. A Review of Pesticide Exposure and Cancer Incidence in the agricultural health study cohort. Environ Health Perspect. 2010;118:1117–25.

10. Alavanja MC, Ward MH, Reynolds P. Carcinogenicity of agricultural pesticides in adults and children. J Agromedicine. 2007;12:39–56.

11. Tarvainen L, Kyyrronen P, Kauppinen T, Pukkala E. Cancer of the mouth and pharynx, occupation and exposure to chemical agents in Finland [in 1971–95]. Int J Cancer. 2008; 123:653–9.

12. Govett G, Genuis SJ, Govett HE, Beesoon S. Chlorinated pesticides and cancer of the head and neck: a retrospective case series. Eur J Cancer. 2011;20:320–5.

13. Costa LGGiordano GGuizzetti MVitalone A. Neurotoxicity of pesticides: a brief review. Front Biosci. 2008;13:1240–9.

14. Robert JR, Karr CJ. Pesticide Exposure in Children; Technical report. Pediatrics. 2012;130:6

15. Yu SJ. The toxicology and biochemistry of insecticides. 2nd ed. Boca Raton, FL: CRC Press, 2014.

16. Ministry of Jihad-e-Agriculture Iran (MOJA). Iran Agricultural Statistics, vol. 1. Crop year 2012-2013. Available from URL: http://www.maj.ir/

portal/ Home/Default.aspx?CategoryID=117564e0-507c-4565-9659-fbabfb4acb9b[accessed September 20, 2014].

17. Nourbakhsh S, Sahraian H, Soroush J, Rezaei V, Fotouhi AR. List of important plant pests, diseases, weeds and recommended pesticide. Karaj, Iran: Agricultural Education Publishing, 2012.

18. Kokouva M, Bitsolas N, Hadjigeorgiou GM, Rachiotis G, Papadoulis N, Hadjichristodoulou C. Pesticide exposure and lymphohaematopoietic cancers: a case-control study in an agricultural region (Larissa, Thessaly, Greece). BMC Public Health. 2011;11:5.

19. Waliszewski SM, Quintana RV, Corona CA, et al. Comparison of organochlorine pesticide levels in human adipose tissue of inhabitants from Veracruz and Puebla, Mexico. Arch Environ Contam Toxicol. 2010;58: 230–6.

20. Covacia A, Boer J, Ryan JK, Voorspoels S, Schepens P. Distribution of organobrominated and organochlorinated contaminants in Belgian human adipose tissue. Environ Res. 2002;88:210–18.

21. U.S. EPA (U.S. Environmental Protection Agency). List of Chemicals Evaluated for Carcinogenic Potential. Availablefrom URL: http://www.epa.gov/pesticides/carlist/ [accessed 1 February 2015].

22. IARC (International Agency for Research on Cancer). IARC monographs on the evaluation of carcinogenic risks to humans. Available from URL: http://www.iarc.fr/en/publications/list/monographs [accessed January 18, 2015].

23. Woo Y-t, Lai DY, Mary F, Argus MF, Arcos JC. 1996. Carcinogenicity of organophosphorus pesticides/compounds: an analysis of their structure‐activity relationships. J Environ Sci Heal C. 1996; 14:1–42.

24. Blasiak J, Jaloszynski P, Trzeciak A, Szyfter K. In vitro studies on the genotoxicity of the organophosphorus insecticide malathion and its two analogues. Mutat Res. 1999;445:275–83.

25. Kim HJ, Park YI, Dong MS. Effects of 2,4-D and DCP on the DHT-induced androgenic action in human prostate cancer cells. Toxicol Sci. 2005;88:52–9.

26. McKinlay R, Plant JA, Bell JNB, Voulvoulis N. Endocrine disrupting pesticides: implications for risk assessment. Environ Int. 2008;34:168–83.

27. Cabello G, Valenzuela M, Vilaxa A, et al. A rat mammary tumor model induced by the organophosphorus pesticides parathion and malathion, possibly through acetylcholinesterase inhibition. Environ Health Perspect. 2001;109:471–9.

28. Isoda H, Talorete TPN, Han J, Oka S, Abe Y, Inamori Y. Effects of organophosphorous pesticides used in China on various mammalian cells. Environ Sci. 2005;12:9–19.

29. Tamura H, Yoshikawa H, Gaido KW, et al. Interaction of organophosphate pesticides and related compounds with the androgen receptor. Environ Health Perspect. 2003;111:545–52.

30. Heinlein CA, Chang, C. Androgen receptor in prostate cancer. Endocr Rev. 2004;25:276–308.

31. Birrell SN, Hall RE, Tilley WD. Role of the androgen receptor in human breast cancer. J Mammary Gland Biol Neoplasia. 1998;3:95–103.

32. Sandal S, Yilmaz B. Genotoxic effects of chlorpyrifos, cypermethrin, endosulfan and 2,4-D on human peripheral lymphocytes cultured rom smokers and nonsmokers. Environ Toxicol. 2011;26:433–42.

33. Amer SM, Aly FAE. Genotoxic effect of 2,4-dichlorophenoxy acetic acid and its metabolite 2,4-dichlorophenol in mouse. Mutat Res. 2001;494:1–12.

34. Padula G, Ponzinibbio MV, Picco S, Seoane A. Assessment of the adverse effects of the acaricide amitraz: in vitroevaluation of genotoxicity. Toxicol Mech Methods. 2012;22:657–61.

35. Radakovic M, Stevanovic J, Djelic N, et al. Evaluation of the DNA damaging effects of amitraz on human lymphocytes in the Comet assay. J Biosci. 2013;38:53–62.

36. Pool-Zobel BL, Leucht U. Induction of DNA damage by risk factors of colon cancer in human colon cells derived from biopsies. Mutat Res. 1997;375:105–15.

37. Liehr JG. Genotoxicity of the steroidal oestrogens oestrone and oestradiol: possible mechanism of uterine and mammary cancer development. Hum Reprod Update. 2001;7: 273–81.

38. Dahmardeh BR, Esmaili Saria A, Bahramifar N, Ghasempouri SM. Organochlorine pesticide and polychlorinated biphenyl residues in human milk from the Southern Coast of Caspian Sea, Iran. Chemosphere. 2009;74:931–37.

39. Moosazadeh M, Khanjani N. Human contamination with organochlorine pesticides in Iran: A systematic review. J Health Develop.2015; 4:76-88.

40. Gobas FAPC, McCorquodale JR, Haffner GD. Intestinal absorption and biomagnification of organochlorines. Environ Toxicol Chem. 1993; 12:567–76.

41. Bagga D, Anders KH, Wang HJ, Roberts E, Glaspy JA. Organochlorine pesticide content of breast adipose tissue from women with breast cancer and control subjects. J Natl Cancer Inst. 2000; 92:750-3.

42. Frigo DE, Tang Y, Beckman BS, et al. Mechanism of AP-1-mediated gene expression by select organochlorines through the p38 MAPK pathway. Carcinogenesis. 2004; 25:249–61.

43. Payne J, Scholze M, Kortenkamp A. Mixtures of four organochlorines enhance human breast cancer cell proliferation. Environ Health Perspect. 2001; 109:391–7.

44. Rattenborg T. Inhibition of E2-induced expression of BRCA1 by persistent organochlorines. Breast Cancer Res. 2002; 4:R12.

45. Mathur V, Bhatnagar P, Sharma RG, Acharya V, Sexana R. Breast cancer incidence and exposure to pesticides among women originating from Jaipur. Environ Int. 2002; 28:331–6.

46. Starek, A. Estrogens and organochlorine xenoestrogens and breast cancer risk. Int J Occup Med Environ Health. 2003; 16:113-24.

47. Thongprakaisang S, Thiantanawat A, Rangkadilok N, Suriyo T, Satayavivad J. Glyphosate induces human breast cancer cells growth via estrogen receptors. Food Chem Toxicol. 2013; 59:129–36.

48. Garry VV. Pesticides and children. Toxicol Appl Pharmacol. 2004; 198:152–63.

49. Anway MD, Cupp AS, Uzumcu M, Skinner MK. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science. 2005; 308:1466–69.

50. Manson JM, Carr MC. Molecular epidemiology of hypospadias: review of genetic and environmental risk factors. Birth Defects Res. Part A CIin Mol Teratol. 2003; 67:825–36.

51. Carozza SE, Li B, Elgethun K, Whitworth R. Risk of childhood cancers associated with residence in agriculturally intense areas in the United States. Environ Health Perspect. 2008; 116:559–65.

52. Santamaría-Ulloa C. The Impact of Pesticide Exposure on Breast Cancer Incidence. Evidence from Costa Rica. Población y Salud en Mesoamérica. 2009;17.

53. Wesseling C, Antich D, Hogsted C, Rodríguez AC, Ahlbom A. Geographical differences of cancer incidence in Costa Rica in relation to environmental and occupational pesticide exposure. Int J Epidemiol. 1999;28:365–74.

54. Van Maele-Fabry G, Willems JL. Prostate cancer among pesticide applicators: a meta-analysis. Int Arch Occup Environ Health. 2004;77: 559–70.

55. Mills PK, Yang R. Breast cancer risk in Hispanic agricultural workers in California. Int J Occup Environ Health. 2005;11: 123–31.

56. Goldsmith DD. Linking environmental cancer with occupational epidemiology research: the role of the international agency for research on cancer (IARC). J Environ Pathol Toxicol Oncol. 2000; 19:171–175.

57. Koutros S, Mahajan R, Zheng T, et al. Dichlorvos exposure and human cancer risk: results from the agricultural health study. Cancer Causes Control. 2008;19:59–65.

58. Lee WJ, Blair A, Hoppin JA, et al. Cancer incidence among pesticide applicators exposed to chlorpyrifos in the Agricultural Health Study. J Natl Cancer Inst. 2004;96:1781–9.

59. Cocco P, Ward MH, Buiatti E. Occupational Risk Factors for Gastric Cancer: an Overview. Epidemiol Rev. 1996;18: 218–35.

60. Gürdal SO, Saraçoğlu GV, Oran EŞ, Yankol Y, Soybir GR. The Effects of educational level on breast cancer awareness: a cross-sectional study in Turkey.Asian Pac J Cancer Prev.2012; 13:295-300.

61. Alavanja MCR, Ross MK, Bonner MR. Increased cancer burden among pesticide applicators and others due to pesticide exposure. CA Cancer J CIin. 2013;63:120–42.

62. Issa YSham'a FANijem KBjertness EKristensen P. Pesticide use and opportunities of exposure among farmers and their families: cross-sectional studies 1998–2006 from Hebron governorate, occupied Palestinian territory. Environ Health. 2010;9:63.

63. Aydin ZD. Sun exposure may confound
physical activity–prostate cancer association. Arch Intern Med. 2005;165:2539–40.

64. Holick MF. Vitamin D and Sunlight: Strategies for Cancer Prevention and Other Health Benefits. CIin J Am Soc Nephrol. 2008;3:1548–54.

65. Wolin KY, Yan Y, Colditz GA. Physical activity and risk of colon adenoma: a meta-analysis. Br J Cancer. 2011;104:882–5.

66. van der Rhee H, Coebergh JW, de Vries E. Is prevention of cancer by sun exposure more than just the effect of vitamin D? A systematic review of epidemiological studies. Eur J Cancer. 2013; 49: 1422–36.