Liver-only metastatic colorectal cancer patients and thymidylate synthase polymorphisms for predicting response to 5-fluorouracil-based chemotherapy.
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 5'-untranslated region (5'-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 3'-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 5'-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.
Graziano
F
F
Medical Oncology, Azienda Ospedaliera Ospedale San Salvatore, Pesaro, Italy. frada@tin.it
Ruzzo
A
A
Loupakis
F
F
Santini
D
D
Catalano
V
V
Canestrari
E
E
Maltese
P
P
Bisonni
R
R
Fornaro
L
L
Baldi
G
G
Masi
G
G
Falcone
A
A
Tonini
G
G
Giordani
P
P
Alessandroni
P
P
Giustini
L
L
Vincenzi
B
B
Magnani
M
M
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000556:secondary*; D008297:Male; D011110:Polymorphism, Genetic; D016019:Survival Analysis; D020080:Tandem Repeat Sequences; D013940:Thymidylate Synthase / Q000235:genetics*; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D013940:Thymidylate Synthase; D005472:Fluorouracil