Thymidylate synthase germline polymorphisms in rectal cancer patients treated with neoadjuvant chemoradiotherapy based on 5-fluorouracil.
OBJECTIVE
Chemoradiotherapy using 5-fluorouracil has shown to be effective treatment for rectal cancer. Thymidylate synthase (TS) is an important target enzyme for the fluoropyrimidines. However, the predictive role of TS levels in early stage rectal cancer is not yet well understood. We analyzed the value of TS gene polymorphisms as a predictive marker in patients with stage II and III rectal cancer treated with preoperative concomitant radiotherapy and fluoropyrimidine-based chemotherapy.


METHODS
Between 1998 and 2007, blood samples were obtained from 51 patients with stage II/III rectal cancer. Forty patients were T2-3 (78%), 11 were T4 (22%), and 59% were N+. DNA was extracted from peripheral blood, and the genotypes were analyzed using PCR-restriction fragment length polymorphism and automated sequencing techniques.


RESULTS
The *3/*3 thymidylate synthase genotype was associated with a higher response rate (pathological complete remission and microfoci residual tumor; 61 vs. 22% in *2/*2 and *2/*3; P = 0.013). In the multivariate analysis, the *3/*3 thymidylate synthase genotype was also an independent prognostic factor for better survival (P < 0.05).


CONCLUSIONS
The thymidylate synthase genotype might help to identify patients with stage II/III rectal cancer who could benefit from pre- and postoperative fluorouracil-based chemotherapy.
Páez
David
D
Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Pare Claret 167, 08025 Barcelona, Spain. dpaez@santpau.cat
Paré
Laia
L
Altés
Albert
A
Sancho-Poch
Francesc Josep
FJ
Petriz
Lourdes
L
Garriga
Jordi
J
Monill
Josep Maria
JM
Salazar
Juliana
J
del Rio
Elisabeth
E
Barnadas
Agustí
A
Marcuello
Eugenio
E
Baiget
Montserrat
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D001483:Base Sequence; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D009367:Neoplasm Staging; D018579:Patient Selection; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D015996:Survival Rate; D013940:Thymidylate Synthase / Q000235:genetics*
D000964:Antimetabolites, Antineoplastic; D004273:DNA, Neoplasm; D013940:Thymidylate Synthase; D005472:Fluorouracil