Patient case: 26-year-old female with chondrosarcoma; genetic feature: IDH1

Clinical trial: Agriculture Health Study

Summary: The "Agricultural Health Study" (AHS) is a collaborative effort between the National Cancer Institute and the National Institute of Environmental Health Sciences. The U.S. Environmental Protection Agency and the National Institute for Occupational Safety and Health are providing support for a limited exposure assessment effort.
  Initial data collection on a prospective cohort of 89,658 study subjects has been completed as of December 1997. Participants completed questionnaires that included items on pesticides used, other agricultural exposures, and work practices that modify exposure as well as on other activities that may affect either exposure or disease risks (e.g., diet, exercise, alcohol consumption, medical conditions, family history of cancer, other occupations and smoking history). Phase II of the study (1998-2003) updated information on occupational exposures, diet, work practices and medical history by means of a computer assisted telephone interview. We also collected buccal cells on sample of 34,000 study participants to assess the effect of inheritable polymorphisms and the interaction of environment and genomic predisposition.
  The stimulus for this prospective investigation comes from the growing evidence that, despite a low mortality overall, farmers experience an excess of several cancers. These excesses have been observed in retrospective epidemiological studies among agricultural workers in several countries. Excess cancers are observed for the lymphatic and hematopoietic system, connective tissue, skin, brain, prostate, stomach and lips. Several of these tumors (brain, NHL, multiple myeloma, and prostate) are also increasing in the general population in many of these countries. This suggests a common set of exposures may explain the high rates in farmers and rising rates in the general population.
  Farmers, their families, and other pest control workers may have contact with a variety of potentially hazardous substances including pesticides, solvents, fuels and oils, engine exhaust, dust and zoonotic viruses and other microbes. Our cohort study includes all registered pesticide applicators in Iowa and North Carolina and the spouse of applicators who are farmers. The health effects of pesticide use are the primary focus of the study. The influence of other farm exposures are also being evaluated.
  The focus of the phase II follow-up period (2004-2008) is to update exposure information and health histories by means of a computer assisted interview and also following the cohort to determine disease incidence and mortality. The cohort is being followed through the cancer registries within Iowa and North Carolina, the Social Security Administration database, state vital statistics offices, National Death Index, and various in-state databases, such as the listing of registered pesticide applicators. Individuals who enrolled into the study but who are no longer at the address given during enrollment (based on subsequent attempts at follow up) have been submitted and will continue to be submitted (through NIOSH) in the standard format to the IRS under their Project 057 Taxpayer Address Request Program. Identifying data provided to the IRS include only SSN and the first four letters of last name of cohort member. IRS provides in return the most current address in IRS records if a match (SSN + all four letter of last name) is found. The purpose of this effort is to identify members of the cohort who have moved out of state, to enable adjustment of person-years for incidence and mortality calculations. Persons who have moved out of state can be followed for vital status and cause of death, but not for cancer incidence.
  Continuation of the protocol will provide a valuable epidemiologic resource to help prevent cancers in the future by identifying risk factors in the rural/agricultural environment. Because more cases of important cancer outcomes occur in this cohort every year, potential cancer causes can be evaluated with increased statistical power. Larger number of cases also allows for statistical control of confounding factors, making more meaningful conclusions about cancer risk, and, for some relatively infrequent cancers, such as the lyphomas and leukemias, greater follow-up time is necessary to make any meaningful observations.

Detailed description: The "Agricultural Health Study" (AHS) is a collaborative effort between the National Cancer Institute and the National Institute of Environmental Health Sciences. The US Environmental Protection Agency and the National Institute for Occupational Safety and Health are providing support for a limited exposure assessment effort.
  Initial data collection on a prospective cohort of 89,656 study subjects has been completed as of December 1997 (Phase I). Participants completed questionnaires that included items on pesticides used, other agricultural exposures, and work practices that modify exposure as well as on other activities that may affect either exposure or disease risks (e.g., diet, exercise, alcohol consumption, medical conditions, family history of cancer, other occupations and smoking history). Phase II of the study (1998-2003) updated information on occupational exposures, diet, work practices and medical history by means of a computer assisted telephone interview. We also collected buccal cells on a sample of 35,164 study participants to assess the effect of inheritable polymorphisms and the interaction of environment and genomic predisposition.
  The stimulus for this prospective investigation comes from the growing evidence that, despite a low mortality overall, farmers experience an excess of several cancers. These excesses have been observed in retrospective epidemiological studies among agricultural workers in several countries. Excess cancers are observed for the lymphatic and hematopoietic system, connective tissue, skin, brain, prostate, stomach and lips. Several of these tumors (e.g., brain, NHL, multiple myeloma, and prostate) are also increasing in the general population in many of these countries. This suggests a common set of exposures may explain the high rates in farmers and rising rates in the general population.
  Farmers, their families, and other pest control workers may have contact with a variety of potentially hazardous substances including pesticides, solvents, fuels and oils, engine exhaust, dust and zoonotic viruses and other microbes. Our cohort study includes all registered pesticide applicators in Iowa and North Carolina and the spouse of applicators who are farmers. The health effects of pesticide use are the primary focus of the study. The influence of other farm exposures is also being evaluated.
  Phase III data collection activity was completed in February 2010. The focus of the phase III follow-up period (2004- 2010) was to update exposure information and health histories by means of a computer assisted interview, to follow the cohort to determine disease incidence and mortality, and to collect buccal cell samples from newly-developing cancer cases (and matched controls) who have not previously donated a sample. Phase III follow-up interviews were completed with 44,130 participants; specifically, interviews were completed with 24,171 applicators and 19,959 spouses. Additionally, 1,245 buccal samples were collected in Phase III from among selected participants with incident cancers. No adverse events were reported during Phase III.
  The cohort continues to be followed through the cancer registries within Iowa and North Carolina, the Social Security Administration database, state vital statistics offices, National Death Index, and various in-state databases, such as the listing of registered pesticide applicators. Individuals who enrolled into the study but who are no longer at the address given during enrollment (based on subsequent attempts at followup) have been submitted and will continue to be submitted (through NIOSH) in the standard format to the IRS under their Project 057 Taxpayer Address Request Program. Identifying data provided to the IRS include only SSN and the first four letters of the last name of the cohort member. IRS provides in return the most current address in IRS records if a match (SSN + all four letters of last name) is found. The purpose of this effort is to identify members of the cohort who have moved out of state, to enable adjustment of person-years for incidence and mortality calculations. Persons who have moved out of state can be followed for vital status and cause of death, but not for cancer incidence.
  Additionally, the Iowa field station maintains a database of AHS cohort children in Iowa established through linkage of the cohort to Iowa birth certificates. This composite of children identified from the Iowa cohort data and birth certificates through 2008 (over 35,000 live births), is linked to Iowa drivers license tapes, the Iowa cancer incidence database, the Iowa mortality database, the NDI, and the Internal Revenue Service (to obtain updated addresses). As with the adult linkages, these data are held by the AHS coordinating center and are available for secondary analysis.
  Continuation of the protocol will provide a valuable epidemiologic resource to help prevent cancers in the future by identifying risk factors in the rural/agricultural environment. Because more cases of important cancer outcomes occur in this cohort every year, potential cancer causes can be evaluated with increased statistical power. Larger numbers of cases also allow for statistical control of confounding factors and more meaningful conclusions about cancer risk, and, for some relatively infrequent cancers, such as the lyphomas and leukemias, greater follow-up time is necessary to make any meaninful observations.
  The process of planning for Phase IV has begun and it is expected to begin before the close of FY2011.

Eligibility: -  INCLUSION CRITERIA:
  All registered pesticide applicators in Iowa and North Carolina and the spouse and children of applicators who are farmers.

Relevance to patient case: not relevant