Changing population characteristics, effect-measure modification, and cancer risk factor identification

Epidemiologic Perspectives & Innovations BioMed Central Analytic Perspective Open Access Changing population characteristics, effect-measure modification, and cancer risk factor identification Martha L Slattery*1, Maureen A Murtaugh1, Charles Quesenberry2, Bette J Caan2, Sandra Edwards1 and Carol Sweeney1 Address: 1University of Utah, School of Medicine, Department of Medicine, Salt Lake City, Utah 84108 USA and 2Kaiser Permanente Medical Research Program, Department of Research, 3505 Broadway, Oakland CA 94611 USA Email: Martha L Slattery* - ; Maureen A Murtaugh - ; Charles Quesenberry - ; Bette J Caan - ; Sandra Edwards - ; Carol Sweeney - * Corresponding author Published: 1 October 2007 Epidemiologic Perspectives & Innovations 2007, 4:10 doi:10.1186/1742-5573-4-10 Received: 11 April 2005 Accepted: 1 October 2007 This article is available from: http://www.epi-perspectives.com/content/4/1/10 © 2007 Slattery et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Epidemiologic studies have identified a number of lifestyle factors, e.g. diet, obesity, and use of certain medications, which affect risk of colon cancer. However, the magnitude and significance of risk factor-disease associations differ among studies. We propose that population trends of changing prevalence of risk factors explains some of the variability between studies when factors that change prevalence also modify the effect of other risk factors. We used data collected from population-based control who were selected as study participants for two time periods, 1991– 1994 and 1997–2000, along with data from the literature, to examine changes in the population prevalence of aspirin and non-steroidal anti-inflammatory medication (NSAID) use, obesity, and hormone replacement therapy (HRT) over time. Data from a population-based colon cancer casecontrol study were used to estimate effect-measurement modification among these factors. Sizeable changes in aspirin use, HRT use, and the proportion of the population that is obese were observed between the 1980s and 2000. Use of NSAIDs interacted with BMI and HRT; HRT use interacted with body mass index (BMI). We estimate that as the prevalence of NSAIDs use changed from 10% to almost 50%, the colon cancer relative risk associated with BMI >30 would change from 1.3 to 1.9 because of the modifying effect of NSAIDs. Similarly, the relative risk estimated for BMI would increase as the prevalence of use of HRT among post-menopausal women increased. In conclusion, as population characteristics change over time, these changes may have an influence on relative risk estimates for colon cancer for other exposures because of effect-measure modification. The impact of population changes on comparability between epidemiologic studies can be kept to a minimum if investigators assess exposure-disease associations within strata of other exposures, and present results in a manner that allows comparisons across studies. Effectmeasure modification is an important component of data analysis that should be evaluated to obtain a complete understanding of disease etiology. Page 1 of 9 (page number not for citation purposes) Epidemiologic Perspectives & Innovations 2007, 4:10 Background Epidemiologic investigations have detected associations between colon cancer and several diet and lifestyle risk factors, but the relative importance of risk factors has changed over time [1,2]. Studies of diet and colon cancer conducted in the early 1980s showed that fat was statistically significantly associated with colon cancer, but more recent studies have not supported that association [3-6]. More recently use of aspirin and hormone replacement therapy (HRT) have emerged as being statistically significant risk factors for colon cancer as well as significantly interacting with other risk factors [7-9]. For example, it has been shown that the association between obesity as indicated by a high body mass index (BMI) and increased relative risk of colon cancer is influenced by estrogen or hormone replacement therapy use [10,11]; reports suggest that aspirin may influence the colon cancer relative risk associated with fat intake [12,13]; other data support the role of effect modification on diet and lifestyle factors in colon cancer etiology [12,14]. Inconsistencies in results for risk factor-disease associations for colon cancer have been attributed to a variety of non-biological factors. Since earlier results for colon cancer came primarily from case-control studies, while cohort studies contributed more to the recent literature, study design, i.e. the potential biased reporting in case-control studies, has been cited as a potential explanation for differences between results of older and more recent studies[15]. However, results of cohort studies may be affected by measurement error from imprecise exposure assessment when data are collected using a self-administered format. Thus case-control and cohort studies each have strengths and weaknesses, yet many risk factor associations are observed to be similar from both case-control and cohort studies. While random and systematic errors may explain differences in study results, even for similar, well-conducted studies, a very plausible explanation for a trend in study results is a change in prevalence of exposures that modify effects of other risk factors. We propose that risk factors associated with colon cancer at the population level exist in a shifting context. We hypothesize that the ability of studies to estimate the influence of risk factors for colon cancer depends on the presence of effect-measure modifiers that are changing in the population. We hypothesize that change in the estimated relative risk from a given exposure can occur if prevalence of other exposures that modify its risk are changing. Thus, it is possible that differences in risk factors identified between studies can be attributed, at least in part, to differences in the prevalence of important population characteristics. http://www.epi-perspectives.com/content/4/1/10 Changes in U.S. population during the last quarter of the 20th century in diet, physical activity, and weight, characteristics that affect colon cancer risk, have been described based on national surveys [16]. In this paper we examine changes in the use of aspirin, HRT, and obesity in population-based samples from two western states between the early 1990s and the late 1990s. Data from these populations were rigorously collected using the same questionnaire and recruitment methods. We evaluate trends in use of HRT and aspirin over the last three decades of the 20th century as reported in the literature and in National Health and Nutrition Examinat (...truncated)