Reply to “The causal association between sarcopenia and colorectal cancer: a Mendelian randomization analysis”
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We appreciate the critical comments by Dr. Ran on our study [1]. Sarcopenia seems to be a very complex clinical condition in which the function and quality of muscles must also be considered, in addition to the loss of muscle mass. Currently, various criteria have been proposed to define sarcopenia, but there are still no clearly unified diagnostic criteria. Therefore, variable diagnostic criteria have been applied in many studies regarding sarcopenia and this could be one of the reasons of the difficulty in studying the relationship between sarcopenia and various diseases [2–4].
Although sarcopenia has been considered as one of aging process, it is also associated with decreased physical activity, dietary habits, and chronic diseases. In addition, these factors could be aggravated by sarcopenia itself. In other words, there are many factors that interact with sarcopenia and those factors directly or indirectly affect each other [5–8]. So, there could be many confounding factors in analyzing the relationship between sarcopenia and specific diseases.
The aim of our study was to evaluate the relationship between sarcopenia and colon neoplasia [8–10]. However, since the criteria for defining sarcopenia are diverse and complex, we defined sarcopenia using three commonly used criteria among the methods that can easily measure, albeit indirectly, in actual clinical practice. And using this, we analyzed the relationship with colon neoplasia. In our study, all measurable confounding factors suggested by various previous studies were adjusted.
The limitation of our study was that we simply considered only muscle mass in sarcopenia and measured muscle mass in an indirect way. Despite these limitations, our results are meaningful in that there was significant relationship between sarcopenia and colon neoplasia after adjusting for all measurable confounding factors, and that possible mechanisms were also inferred through previous studies [11–19].
It is very interesting that the results of Medelian randomization analysis using genetic variation on the relationship between sarcopenia and colon neoplasia yielded results opposite to those of our study. We believe that the results of your study are also meaningful in that Medelian randomization analysis has little influence of confounding factors and can evaluate causality between exposure and outcome. However, there are also limitations in predicting the relationship between sarcopenia and colon neoplasia simply with genetic variation. In other words, the reason why the result of your study was different from ours is that our study analyzed based on various clinical factors rather than genetic factors. Although we cannot know which one has more powerful impact on the development of colorectal neoplasia, we think that race, age, and other acquired factors also must be fully considered because the development of colorectal neoplasia is associated with both genetic and environ mental factors.
In summary, sarcopenia is a very complex clinical condition that interacts with various factors, and some of those factors are also related to the development of colorectal neoplasia, so it can be difficult to find a clear association between sarcopenia and colorectal neoplasia. We analyzed the relationship considering various clinical factors rather than genetic variation. On the other hand, Dr. Ran analyzed the relationship based on genetic factors. Difference in these research approaches or methods led to different results, and more research is needed on this.
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No potential conflict of interest relevant to this article was reported.