CAPP2 RCT: Resistant Starch Planned Long-term Follow-up—Letter

We read with great interest the article by Mathers and colleagues (1) on the large impact of resistant starch intake on the extracolonic cancer risk in Lynch syndrome (LS). Even though these analyses did not confirm the original hypothesis when starting this intervention study, that is, no impact on colon cancer risk was found, the outcomes of this study should be taken into account when formulating lifestyle advice because extracolonic cancers are more difficult to detect with screening.Although the size of the cohort and follow-up time is impressive and numbers are convincing, some questions came up, which need to be answered before specific dietary recommendations can be given to patients with LS.In fact, LS is a composite term for several hereditary disorders. Germline pathogenic variants in the MLH1, MSH2 (including Epcam) MSH6, and PMS2 mismatch repair genes all lead to an increased cancer risk. As shown by the ongoing European PLSD study (2), cancer risk for these genes differs considerably though. The lifetime risk for colon cancer is highest in patients with germline MLH1 and MSH2 LS and the risk for extracolonic cancer is by far the highest for MSH2 LS and lowest for PMS2 LS (2, 3). For example, the lifetime risk for urothelial cancer is about 18% in MSH2 LS, and only about 4% for MLH1 and MSH6 LS (2, 3). For PMS2 LS, the risk is not significantly higher than in the general population (4).Most patients with LS in the cohort of Mathers and colleagues are patients with a MLH1 453/758 (60%) or MSH2 germline variant 280/758 (37%), and only few MSH6 25/758 (3%) and no PMS2 variant carriers were included (1). The question therefore remains what the effect of the use of resistant starch in patients with MSH6 and PMS2 LS is. And whether there was difference in effect between MLH1 and MSH2 variant carriers in this study.Also, the question is whether the effect of the used Novelose powder on cancer risk is also observed when eating resistant starch by consuming bananas, pulses, and other foods containing this kind of starch, which might be relevant when giving dietary advice to patients with LS in daily practice.These questions should be taken into account when advising patients with Lynch syndrome and writing guidelines.See the Response, p. 59No disclosures were reported.