セロトニン関連遺伝子多型とがん化学療法に伴う消化器症状の発現との関連性

抄録

Chemotherapy-induced gastrointestinal symptoms are one of the most distressing adverse side effects. To address this, serotonin (5-HT) 5-HT₃ receptor antagonists are recommended before chemotherapy and indicated when breakthrough chemotherapy-induced gastrointestinal symptoms occur. However, not all patients obtain sufficient effects with serotonin receptor antagonists. To provide precision medicine, we examined the relationship between the frequency or intensity of chemotherapy-induced gastrointestinal symptoms and polymorphisms of serotonin-related genes. We examined the association between gene polymorphisms and gastrointestinal symptoms in 55 patients with cancer who were undergoing chemotherapy at Nagoya University Hospital. Anorexia, nausea, and vomiting were graded based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. We found that the frequency and intensity of chemotherapy-induced gastrointestinal symptoms were associated with the gene polymorphisms of 5HTTLPR [serotonin transporter gene (SLC6A4)] and haplotype of VNTR [monoamine oxidase A gene (MAOA)]-rs1799836 [monoamine oxidase B gene (MAOB)]. Frequency was also associated with the gene polymorphism of VNTR (MAOA). Our study showed that certain gene polymorphisms were associated with the frequency and intensity of chemotherapy-induced gastrointestinal symptoms. These findings can help in the development of precision medicine for chemotherapy-induced side effects.