) Histamine (H2) blockers, such as cimetidine and ranitidine, first became available in the late 1970s and currently number among the most commonly prescribed drugs. Preventive effects of cimetidine on the risk of prostate and other hormonally-mediated cancers have been hypothesized based on the drug's influence on androgen binding and estrogen metabolism. The investigators propose to conduct a retrospective cohort study to assess risk of hormonally-mediated cancers (including prostate, breast, and endometrial) in users of H2 blockers identified within the membership of the Group Health Cooperative (GHC) of Puget Sound. The GHC pharmacy database will be used to identify a cohort of individuals prescribed H2 blockers between 1977 and 1995, and to assess the type, dosage, and duration of use of these drugs. The occurrence of cancer in cohort members will be identified using data provided by the Cancer Surveillance System of Western Washington (CSS), a population-based cancer registry. Standardized incidence ratios will be calculated comparing the observed numbers of cancers in the cohort overall and in subgroups (e.g., by specific drug used) to those expected based on age- and sex-specific population rates reported by the CSS. Because only cimetidine, and not ranitidine or other H2 blockers, influences hormonal activity and metabolism, the investigators will also assess the risk of hormonally-mediated cancers among individuals treated with cimetidine relative to that of individuals who exclusively used other H2 blockers. Such analyses will reduce the possibility that study results are influenced by confounding by indication of treatment. The proposed research will: (1) provide valuable analyses of considerable public health importance relevant to cancer prevention, in an area in which insufficient previous research has been conducted; (2) provide preliminary data that will allow an assessment of the need for further research; and (3) direct the design of future epidemiologic and intervention studies of this hypothesis.
