The role and limitations of retrospective investigations of factors possibly associated with the occurrence of a disease are discussed and their relationship to forward-type studies emphasized. Examples of situations in which misleading associations could arise through the use of inappropriate control groups are presented. The possibility of misleading associations may be minimized by controlling or matching on factors which could produce such associations; the statistical analysis will then be modified. Statistical methodology is presented for analyzing retrospective study data, including chi-square measures of statistical significance of the observed association between the disease and the factor under study, and measures for interpreting the association in terms of an increased relative risk of disease. An extension of the chi-square test to the situation where data are subclassified by factors controlled in the analysis is given. A summary relative risk formula, R, is presented and discussed in connection with the problem of weighting the individual subcategory relative risks according to their importance or their precision. Alternative relative-risk formulas, RI , R2, Ra, and R4/ which require the calculation of subcategory-adjusted proportions ot the study factor among diseased persons and controls for the computation of relative risks, are discussed. While these latter formulas may be useful in many instances, they may be biased or inconsistent and are not, in fact, overages of the relative risks observed in the separate subcategories. Only the relative-risk formula, R, of those presented, can be viewed as such an average. The relationship of the matched-sample method to the subclassification approach is indicated. The statistical methodolo~y presented is illustrated with examples from a study of women with epidermoid and undifferentiated pulmonary ccrclnomc.e
The premalignant process in the gastric mucosa was studied by gastroscopic surveys of Colombian populations, and the prevalence of superficial gastritis, chronic atrophic gastritis, and intestinal metaplasia was calculated for population samples having a very high gastric cancer risk (Nariño), very low risk (Cartagena), and intermediate risk (Cali). The prevalence of individuals with normal mucosa in successive age groups was used to estimate "depletion" curves, which were taken as indicators of the dynamics of the premalignant process in each community. Differences corresponding to the geographic variation in stomach cancer risk were found: In the high-risk areas of Nariño, around 75% of the population developed some type of gastritis by 45 years of age, whereas in the low- and intermediate-risk population of Cartagena and Cali, the proportion of such lesions did not exceed 50% at age 45 or thereafter. The effect of environmental factors in early life seemed to be important in determining the prevalence of lesions in each population.
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