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most cancers, the lag between exposure and diagnosis is at least 10 years; however, there are exceptions, such as leukemia. Eliminating study participants who died from cancer that occurred within 10 years of exposure should increase the SMR if there is a true association between exposure to the agent and the cancer. Conversely, the case for an association is much weaker when the death rate relative to that in the US population is the same whether or not the author considered the early cancer deaths.

Specificity of Outcome

The study had to specify a distinct outcome rather than a nonspecific group of health outcomes. Lack of specificity occurs primarily in mortality studies that examine all-cause mortality (such as deaths from all types of cancer) as opposed to cause-specific mortality (such as deaths from lung cancer). All-cause mortality studies were excluded unless they analyzed specific health outcomes.

Adverse Clinical Outcomes

After reviewing the approximately 1,000 articles in the reference database, the committee focused on a number of relevant health outcomes on which to draw conclusions (see Chapters 6 and 8). The selected health outcomes are 10 types of cancer and several nonmalignant diseases or conditions. The types of cancer are lung cancer, leukemia, lymphoma, bone cancer, renal cancer, bladder cancer, brain and other central nervous system cancers, stomach cancer, prostatic cancer, and testicular cancer; the nonmalignant diseases or conditions include renal disease, respiratory disease, neurologic disease, and reproductive and developmental effects. With the exception of prostatic and testicular cancers, the health outcomes were selected by the committee because there are plausible mechanisms of action (for example, lung cancer and respiratory disease were selected because inhaled insoluble uranium oxides lodge in the lung). Prostatic cancer is the most frequently diagnosed cancer in men in the United States, and any slight increase in risk could result in large numbers of cases and deaths. Testicular cancer, the most common cancer in young men, is of special interest to Gulf War veterans, and some recent studies of veterans suggested a higher but nonsignificant risk in them than in their nondeployed counterparts (IOM, 2006).

Considerations in Statistical Inference

Tests of Association

Studies of a possible relationship between an exposure of interest and an outcome typically report statistical tests of association. Those tests assess whether the data are consistent with the claim of an association between exposure and outcome. The association is commonly expressed in terms of null and alternative



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