DPYD and TYMS polymorphisms as predictors of 5 fluorouracil toxicity in colorectal cancer patients.

Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer death. 5-Fluorouracil (5-FU) is an essential component of systemic chemotherapy for CRC. Our objective was to determine the genotypic frequency of polymorphisms affecting dihydropyrimidine dehydrogenase (DPYD) and thymidylate synthetase (TYMS) genes and to correlate the genetic profile with the toxicity due to 5-FU, also considering nongenetic factors. This is a prospective study that involved 66 patients. We extracted DNA by salting out methods. We carried out the genotyping of the different polymorphisms by simple PCR for the TYMS 5'UTR and by PCR-RFLP for DPYD: 1905 + 1 G > A, 85 T > C, 496 A > G, 1679 T > G, c.483 + 18G > A and the TYMS: 5'UTR VNTR, 5'UTR G > C and 3'UTR. The study of the association of DPYD and TYMS polymorphisms with the various signs of toxicity under 5-FU revealed that the polymorphisms 496 A > G were significantly associated with hepatotoxicity: OR = 3.85 (p = 0.04). In addition, 85 T > C was significantly associated with mucositis and neurotoxicity: OR = 4.35 (p = 0.03), OR = 3.79 (p = 0.02). For TYMS, the only significant association we observed for 5'UTR with vomiting: OR = 3.34 (p = 0.04). The incidence of adverse reactions related to 5-FU appears to be influenced in patients with CRC by the identified DPYD and TYMS gene polymorphisms in the Tunisian population.

Effect of chemotherapy on autoimmune hepatitis in thymoma: a case report and literature review.

Autoimmune hepatitis (AIH) has rarely been described as an autoimmune paraneoplastic syndrome of thymoma. This case is the seventh case of AIH revealed by cholestasis few years after the diagnosis of thymoma and the first case treated with chemotherapy alone. We report in this paper a new approach to this rare severe condition. A 29 year-old man presented with chest pain and dyspnea with a history of thymoma surgically removed 4 years ago. CT scan showed the recurrence of an anterior mediastinal mass. Biology showed elevated liver enzymes and profound cholestasis. No sign of viral or toxic hepatitis or bile duct abnormalities were observed. Autoimmune antibodies, except for the anti-nuclear antibody, were negative. Liver biopsy showed active chronic AIH. The patient was diagnosed with recurrent thymoma with AIH and underwent 6 cycles of chemotherapy. A complete response on thymoma and cholestasis was obtained after 10 months of follow-up. Steroids and immunosuppressors are the standard treatment for AIH. The effect of chemotherapy as a specific treatment of this paraneoplastic syndrome needs to be considered.