We appreciate the opportunity to respond to the letter from Bilir and Engin regarding our article. They raise the important issue that the patient treated with amiodarone has a much higher intake of iodine compared with a patient with a regular diet. We agree that BRAF mutations may play an important role in amiodarone-induced carcinogenesis. The frequency of BRAF mutations varies widely in human cancers, being identified in 59% of melanomas, 18% of colorectal cancers, 11% of gliomas, 9% of sarcomas, 7% of liver cancers, 3% of lung cancers, and 2% of ovarian cancers. Greater than 90% of the observed mutations in BRAF result in the substitution of glutamic acid for valine at codon 600 (BRAF V600E mutation) and a number of researchers have pinpointed BRAF V600E mutation as a likely driver mutation in melanoma,[3, 4] colorectal cancer, thyroid cancer, hairy cell leukemia, etc. Further studies are required to clarify whether there is a link between amiodarone and BRAF mutations.
The effect of amiodarone on carcinogenesis may be more significant in patients with cancers of the digestive tract, lung cancer, thyroid cancer, and skin cancer than in those with other cancers because amiodarone may induce hepatitis, interstitial lung disease, thyrotoxicity, and photosensitivity, and these local inflammatory effects could predispose patients to the development of cancer. Nonetheless, the expected increased risk of specific cancer types was not observed in our study, although with a large person-time of observation might be explained by the limited follow-up duration. Our study focused on the risk of cancer in patients treated with amiodarone but did not clarify the mechanism. The result of our study may be biased due to its retrospective study design and therefore more research is needed.
Vincent Yi-Fong Su, MD
Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
Yu-Wen Hu, MD
Cancer Center, Taipei Veterans General Hospital; School of Medicine, National Yang-Ming University; Institute of Public Health, National Yang-Ming University, Taipei, Taiwan
Chia-Jen Liu, MD
Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital; School of Medicine, National Yang-Ming University, Taipei, Taiwan;
Department of Internal Medicine, National Yang-Ming University Hospital, Yilan, Taiwan;
Institute of Public Health, National Yang-Ming University, Taipei, Taiwan