Veterans and Agent Orange: Update 1996

The importance of latency effects and other time-related factors in determining cancer risk has long been recognized, and statistical methodologies have been developed to study this issue. A variety of practical difficulties relating to exposure assessment and other data requirements, however, have limited the use of these methods in epidemiological studies of environmental carcinogens. In response to the request from the DVA to explore latency issues related to herbicides used in Vietnam, the committee attempts in Chapter 8 to establish a methodology to address the timing of herbicide exposure and the risk of cancer. This chapter also reviews the literature on herbicide exposure and cancers classified in the "Sufficient Evidence of an Association" and "Limited/Suggestive Evidence of an Association" categories for results that describe how timing of exposure affects the relative risk due to exposure.

For four of the cancers studied--soft-tissue sarcoma, non-Hodgkin's lymphoma, Hodgkin's disease, and multiple myeloma--the committee concluded that there was not enough information in the literature about the timing of exposure and subsequent risk to further discuss latency issues. The committee did find that there was enough information about the timing of exposure and respiratory and prostate cancers, with considerably more information about the former than the latter, to warrant analysis of results. Both of these cancers are in the "Limited/Suggestive Evidence of an Association" category, and this conclusion has not changed after this investigation of time-related factors.

The evidence in the literature suggests that the time from exposure to TCDD to increased risk of respiratory cancer is less than ten years, and that the increase in relative risk continues for somewhat more than 20 years. The available literature does not indicate how long it takes for relative risks to return to one. These conclusions are based primarily on the study conducted by the National Institute for Occupational Safety and Health (Fingerhut, 1991), since this study is the most informative about the changes in risk of respiratory cancer with time since first exposure to TCDD, but the calculations are supported by other studies that have investigated time-related effects. The epidemiological literature was not informative on the effect of the age at which the exposure was received, or whether the carcinogen appeared to act at an early or late stage of the carcinogenic process.

The limited data do not indicate any increase in the relative risk of prostate cancer with time since exposure to TCDD. For prostate cancer, the epidemiological literature was not informative on how long the effects of exposure last, the effect of the age at which the exposure was received, or whether the carcinogen acts at an early or late stage of the carcinogenic process.