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 case-control 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. Effect-measure modification is an important component of data analysis that should be evaluated to obtain a complete understanding of disease etiology.
Highlights
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]
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]
The prevalence of aspirin use dramatically increased between population-based studies conducted in the late 1970s and early 1980s, in which use was reported at 7% [26] and 15% [27] respectively, and one conducted in 1997–2000, in which use was over 40%
Summary
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]. 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]. 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
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