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NCI case-control studies

During the 1980s, the U.S. National Cancer Institute (NCI) conducted three case-control studies in four mid-western states (Iowa, Minnesota, Kansas, and Nebraska) to evaluate pesticides and cancer at multiple sites. Non-Hodgkin lymphoma was evaluated in all three studies. Additionally, in the Kansas study, Hodgkin lymphoma and soft tissue sarcoma were included, while in the Iowa/Minnesota study, multiple myeloma was included, and in the Nebraska study, Hodgkin lymphoma, multiple myeloma and chronic lymphocytic leukemia were evaluated.   

Men and women who were diagnosed with these cancers during the study years were recruited from area hospitals and cancer registries. Women were only included in the study in Nebraska. Controls were selected from the general population by random digit dialing, random listings from Medicare, and from state mortality files. Cases and controls were matched on a variety of criteria such as age, state, sex, race, and other variables that may be associated with both agricultural exposures and the different types of cancers that were evaluated. Telephone and in person questionnaires, as well as pesticide suppliers’ surveys, were used to obtain pesticide exposure data and other information related to the different cancer types. In each case-control study, participants were asked detailed questions about the use of agricultural pesticides, farming practices, and exposure to other known or suspected risk factors for the cancer site under study. These interviewer-administered questionnaires were conducted by telephone and in person with cases and controls, and can be found in the links below. To evaluate possible recall bias of self-reported pesticide use, pesticide suppliers were asked to provide information on crops and pesticide purchases for a sample of subjects with farming experience.

Early results from the individual studies showed an association between 2,4-D use and non-Hodgkin lymphoma. More recently, data from the non-Hodgkin lymphoma studies have been pooled to include approximately 1000 cases and 3000 controls. Many analyses have been conducted on this large dataset to assess various hypotheses about the development of non-Hodgkin lymphoma. These have shown increased risks from exposure to several individual pesticides, including 2,4-D, lindane, malathion, carbaryl, and DDT, as well as from exposure to multiple pesticides. Several studies demonstrated that pesticides may contribute to the development of non-Hodgkin lymphoma through mechanisms that involve chromosomal abnormalities. Furthermore, there was some evidence that asthma modified the association between pesticide exposure and the risk of this cancer.

Key findings for other cancer sites suggest potentially important roles for pesticides and other factors on cancer risk. For example, the use of insecticides on animals was linked to an increase in risk of soft tissue sarcoma. Non-occupational factors, such as family history of cancer, also elevated the risk of soft tissue sarcoma. There was little evidence to support associations between farming or pesticides and the risks of multiple myeloma or Hodgkin lymphoma, however, the use of hair coloring products among women was related to increased odds of these two cancer sites.

The methodologies used in the NCI case-control studies are described in detail in the publications below.

 

Questionnaires

In each case-control study, participants were asked detailed questions about the use of agricultural pesticides, farming practices, and exposure to other known or suspected risk factors for the cancer site under study. These interviewer-administered questionnaires were conducted by telephone and in person with cases and controls. To evaluate the validity of self-reported pesticide use, pesticide suppliers were asked to provide information on crops and pesticide purchases for a sample of subjects with farming experience. The questionnaires used in each study are below.

Iowa and Minnesota Questionnaire

Nebraska Questionnaire

Kansas Questionnaire

 

Current analyses

There are currently no analyses in progress.

 

Publications

  1. Hoar SK, Blair A, Holmes FF, Boysen CD, Robel RJ, Hoover R, Fraumeni JF Jr. Agricultural herbicide use and risk of lymphoma and soft-tissue sarcoma.  Journal of the American Medical Association 1986;256:1141-1147.
  2. Dick FR, Van Lier SF, McKeen K, Everett GD, Blair A. Nonconcurrence in abstracted diagnoses of non-Hodgkin’s lymphoma.  Journal of the National Cancer Institute 1987;78:675-678.
  3. Dick F, Van Lier S, Banks P, Frizzera G, Witrak G, Gibson R, Everett G, Schuman L, Isacson P, O’Conor G, Cantor K, Blattner W, Blair A.  Use of the working formulation for non-Hodgkin’s lymphoma in epidemiologic studies: agreement between reported diagnoses and a panel of experienced pathologists. Journal of the National Cancer Institute 1987;78:1137-1144.
  4. Cantor KP, Blair A, Everett G, Van Lier S, Burmeister L, Dick FR, Gibson RW, Schuman L.  Hair dye use and risk of leukemia and lymphoma.  American Journal of Public Health 1988;78:570-571.
  5. Zahm SH, Blair A, Holmes FF, Boysen CD, Robel RJ. A case-referent study of soft-tissue sarcoma and Hodgkin’s disease: Farming and insecticide use.  Scandinavian Journal of Work, Environment, and Health 1988;14:224-230.
  6. Zahm SH, Blair A, Holmes FF, Boysen CD, Robel RJ, Fraumeni JF Jr. A case-control study of soft-tissue sarcoma.  American Journal of Epidemiology 1989;130:665-674.
  7. Linos A, Blair A, Cantor KP, Burmeister L, Van Lier S, Gibson RW, Schuman L, Everett G. Leukemia and non-Hodgkin’s lymphoma among embalmers and funeral directors (letter).  Journal of the National Cancer Institute 1990;82:66.
  8. Zahm SH, Weisenburger DD, Babbitt PA, Saal RC, Vaught JB, Cantor KP, Blair A. A case-control study of non-Hodgkin’s lymphoma and the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) in eastern Nebraska.  Epidemiology 1990;1:349-356.
  9. Weisenburger DD. Environmental epidemiology of non-Hodgkin’s lymphoma in eastern Nebraska. American Journal of Industrial Medicine 1990;18:303-305.
  10. Linos A, Blair A, Gibson RW, Everett G, Van Lier S, Cantor KP, Schuman L, Burmeister L. Leukemia and non-Hodgkin’s lymphoma and residential proximity to industrial plants.  Archives of Environmental Health 1991;46:70-74.
  11. Pottern LM, Linet M, Blair A, Dick F, Burmeister LF, Gibson R, Schuman LM, Fraumeni JF Jr. Familial cancers associated with subtypes of leukemia and non-Hodgkin’s lymphoma.  Leukemia Research 1991;15:305-314.
  12. Brown LM, Everett GD, Gibson R, Burmeister LF, Schuman LM, Blair A. Smoking and risk of non-Hodgkin’s lymphoma and multiple myeloma.  Cancer Causes & Control 1992;3:49-55.
  13. Cantor KP, Blair A, Everett G, Gibson R, Burmeister LF, Brown LM, Schuman L, Dick FR. Pesticides and other agricultural risk factors for non-Hodgkin’s lymphoma among men in Iowa and Minnesota.  Cancer Research 1992;52:2447-2455.
  14. Zahm SH, Weisenburger DD, Babbitt PA, Saal RC, Vaught JB, Blair A. Use of hair coloring products and the risk of lymphoma, multiple myeloma, and chronic lymphocytic leukemia.  American Journal of Public Health 1992;82:990-997.
  15. Blair A, Linos A, Stewart PA, Burmeister LF, Gibson R, Everett G, Schuman L, Cantor KP. Comments on occupational and environmental factors in the origin of non-Hodgkin’s lymphoma.  Cancer Research 1992;52:5501-5502s.
  16. Brown LM, Everett GD, Burmeister LF, Blair A. Hair dye use and multiple myeloma in white men.  American Journal of Public Health 1992;82:1673-1674.
  17. Brown LM, Gibson R, Burmeister LF, Schuman LM, Everett GD, Blair A. Alcohol consumption and risk of leukemia, non-Hodgkin’s lymphoma, and multiple myeloma.  Leuk Res 1992;16:979-84.
  18. Blair A, Zahm SH. Patterns of pesticide use among farmers: Implications for epidemiologic research.  Epidemiology 1993;4:55-62.
  19. Blair A, Linos A, Stewart PA, Burmeister LF, Gibson R, Everett G, Schuman L, Cantor KP. Evaluation of risks of non-Hodgkin’s lymphoma by occupation and industry exposures from a case-control study.  American Journal of Industrial Medicine 1993;23:301-312.
  20. Brown LM, Burmeister LF, Everett GD, Blair A. Pesticide exposures and multiple myeloma in Iowa men.  Cancer Causes & Control 1993;4:153-156.
  21. Zahm SH, Weisenburger DD, Cantor KP, Holmes FF, Blair A. Role of the herbicide atrazine in the development of non-Hodgkin’s lymphoma.  Scandinavian Journal of Work, Environment, and Health 1993;19:108-114.
  22. Cantor KP, Blair A, Brown LM, Burmeister LF, Everett G. Correspondence Re – Pesticides and other agricultural risk factors for non-Hodgkin lymphoma among men in Iowa and Minnesota (letter). Cancer Research 1993;53:2421s.
  23. Ward MH, Zahm SH, Weisenburger DD, Gridley G, Cantor KP, Saal RC, Blair A. Dietary factors and non-Hodgkin’s lymphoma in Nebraska (United States).  Cancer Causes & Control 1994;5:422-432.
  24. Zahm SH, Weisenburger DD, Cantor KP, Holmes FF, Blair A.  Non-Hodgkin’s lymphoma and use of atrazine:  results from three case-control studies.  In: McDuffie HH, Dosman JA, Semchuk D, Olenchock S, Senthilselvan A, eds. Agricultural health and safety: workplace, environment and sustainability.  Boca Raton: CRC Lewis Publishers, 1995;151-156.
  25. Ward MH, Zahm SH, Weisenburger DD, Saal R, Cantor KP, Blair A.  Diet and drinking water source:  association with non-Hodgkin’s lymphoma in eastern Nebraska.  In:  McDuffie HH, Dosman JA, Semchuk K, Olenchock S, Senthilselvan A, eds. Agricultural health and safety: workplace, environment, sustainability. Boca Raton: CRC Press, Inc., 1995;143-150.
  26. Zahm SH, Weisenburger DD, Holmes FF, Cantor KP, Blair A. Tobacco and non-Hodgkin’s lymphoma: Combined analysis of three case-control studies (United States). Cancer Causes & Control 1997;8:159-166.
  27. Baris D, Zahm SH, Cantor KP, Blair A. Agricultural use of DDT and risk of non-Hodgkin’s lymphoma: Pooled analysis of three case-control studies in the United States. Occupational and Environmental Medicine 1998;55:522-527.
  28. Blair A, Cantor KP, Zahm SH. Non-Hodgkin’s lymphoma and agricultural use of the insecticide lindane. American Journal of Industrial Medicine 1998;33:82-87.
  29. Waddell BL, Blair A, Zahm SH. Re: Relation of cigarette smoking to non-Hodgkin’s lymphoma among middle-aged men. American Journal of Epidemiology 1999;150:661-662.        
  30. Waddell BL, Zahm SH, Baris D, Weisenburger DD, Holmes F, Burmeister LF, Cantor KP, Blair A. Agricultural use of organophosphate pesticides and the risk of non-Hodgkin’s lymphoma among male farmers (United States). Cancer Causes & Control 2001;12:509-517.
  31. Schroeder JC, Olshan AF, Baric R, Dent GA, Weinberg CR, Yount B, Cerhan JR, Lynch CF, Schuman LM, Tolbert PE, Rothman N, Cantor K, Blair A. Agricultural risk factors for t(14;18) subtypes of non-Hodgkin’s lymphoma. Epidemiology 2001;12:701-709.  
  32. Zheng T, Zahm SH, Cantor KP, Weisenburger DD, Zhang Y, Blair A. Agricultural exposure to carbamate pesticides and risk of non-Hodgkin lymphoma. Journal of Occupational and Environmental Medicine 2001;43:641-649.
  33. Schroeder J, Olshan A, Baric R, Dent G, Weinberg C, Yount B, Cerhan J, Lynch C, Schuman L, Tolbert P, Rothman N, Cantor K, Blair A. A case-control study of tobacco use and other non-occupational risk factors for t(14;18) subtypes of non-Hodgkin’s lymphoma (United States). Cancer Causes & Control 2002;13:159-168. 
  34. Zheng T, Blair A, Zhang Y, Weisenburger DD, Zahm SH. Occupation and risk of non-Hodgkin’s lymphoma and chronic lymphocytic leukemia. Journal of Occupational and Environmental Medicine 2002;44:469-474. 
  35. Chiu BCH, Weisenburger DD, Cantor KP, Zahm SH, Holmes F, Burmeister LF, Blair A. Alcohol consumption, family history of hematolymphoproliferative cancer, and the risk of non-Hodgkin’s lymphoma in men.  Annals of Epidemiology 2002;12:309-315.
  36. DeRoos AJ, Zahm SH, Weisenburger DD, Holmes FF, Burmeister LF, Blair A. Integrative assessment of multiple pesticides as risk factors for non-Hodgkin’s lymphoma among men.  Occupational and Environmental Medicine 2003;60. 
  37. Chiu BC-H, Weisenburger DD, Zahm SH, Cantor KP, Gapstur SM, Holmes FF, Burmeister LF, Blair A. Agricultural pesticide use, familial cancer, and risk of non-Hodgkin’s lymphoma.  Cancer Epidemiology, Biomarkers, and Prevention 2004;13:525-531.
  38. Lee WJ, Cantor KP, Berzofsky JA, Zahm SH, Blair A. Risk of non-Hodgkin’s lymphoma among asthmatic subjects exposed to pesticides. International Journal of Cancer 2004;111:298-302.
  39. Chiu B,Dave BJ,  Blair A, JS, Gapstur SM, Chmiel JS, Fought AJ, Zahm SH, Weisenburger DD. Cigarette smoking, familial hematopoietic cancer, hair dye use, and risk of t(14;18)-defined subtypes of non-Hodgkin lymphoma. American Journal of Epidemiology 2007;165:652-659.
  40. Chiu BC-H, Lan Q, Dave BJ, Blair A, Zahm SH, Weisenburger DD. The utility of t(14;18) in understanding risk factors for non-Hodgkin lymphoma.  Journal of the National Cancer Institute Monographs 2008;39:69-73.
  41. Chiu BCH, Dave BJ, Ward MH, Hou L, Fought AJ, Jain S, Evens AM, Zahm SH, Blair A, Weisenburger DD.  Dietary factors and risk of t(14;18)-defined subgroups of non-Hodgkin lymphoma.  Cancer Causes & Control 2008;19:859-867.
  42. Chiu BC-H, Blair A.  Pesticides, chromosomal aberrations, and non-Hodgkin’s lymphoma.  Journal of Agromedicine 2009;14 :250-255.
  43. Chang CM, Schroeder JC, Dunphy CH, Baric RS, Olshan AF, Dorsey KC, Huang W-Y, Blair A.  Non-Hodgkin lymphoma (NHL) subtypes defined by common translocations: Utility of fluorescence in situ hybridization (FISH) in a case-control study.  Leukemia Research 2010;34:190-195.
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