We investigated the association between thymidylate synthase (TS) germline polymorphisms and response to 5-fluorouracil-based chemotherapy in 80 patients with liver-only metastatic colorectal cancer (MCRC). The tandem repeat polymorphism ( VNTR) in TS 50-untranslated region ( 50-UTR), which consists of two ( 2R) or three ( 3R) 28-bp repeated sequences, with or without a G/C nucleotide change in 3R carriers ( 3G or 3C) and a 6-bp insertion/deletion (6+/6-) in the TS 30-UTR, was studied. The distinction between high ( 2R/3G, 3C/3G and 3G/3G) and low ( 2R/2R, 2R/3C and 3C/3C) TS expression genotypes according to the 50-UTR VNTR+G/C nucleotide change showed significant association with tumour response ( P = 0.01). In particular, high TS expression genotypes were found in 8 out of 34 patients ( 23.5%) with complete or partial response and in 24 out of 46 patients ( 52%) with stable disease and disease progression. Liver-only MCRC patients are a homogeneous and clinical relevant subgroup that may represent an ideal setting for studying the actual influence of TS polymorphisms.

Liver-only metastatic colorectal cancer patients and thymidylate synthase polymorphisms for predicting response to 5-fluorouracil-based chemotherapy

RUZZO, ANNAMARIA;MAGNANI, MAURO
2008-01-01

Abstract

We investigated the association between thymidylate synthase (TS) germline polymorphisms and response to 5-fluorouracil-based chemotherapy in 80 patients with liver-only metastatic colorectal cancer (MCRC). The tandem repeat polymorphism ( VNTR) in TS 50-untranslated region ( 50-UTR), which consists of two ( 2R) or three ( 3R) 28-bp repeated sequences, with or without a G/C nucleotide change in 3R carriers ( 3G or 3C) and a 6-bp insertion/deletion (6+/6-) in the TS 30-UTR, was studied. The distinction between high ( 2R/3G, 3C/3G and 3G/3G) and low ( 2R/2R, 2R/3C and 3C/3C) TS expression genotypes according to the 50-UTR VNTR+G/C nucleotide change showed significant association with tumour response ( P = 0.01). In particular, high TS expression genotypes were found in 8 out of 34 patients ( 23.5%) with complete or partial response and in 24 out of 46 patients ( 52%) with stable disease and disease progression. Liver-only MCRC patients are a homogeneous and clinical relevant subgroup that may represent an ideal setting for studying the actual influence of TS polymorphisms.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11576/1883475
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