Role of a DT-diaphorase mutation in the response of anal canal carcinoma to radiation, 5-fluorouracil, and mitomycin C.
OBJECTIVE
To determine, retrospectively, the status of the bp 609 mutation in the DT-diaphorase gene in anal canal carcinoma patients who have undergone radical radiotherapy with concurrent 5-fluorouracil (5-FU) and mitomycin C (MMC), to determine the relationship of the mutant form of the gene to treatment outcomes.


METHODS
Paraffin blocks of pretreatment tumor biopsies were obtained on 49 patients who underwent treatment with curative intent using radiation, infusional 5-FU and bolus MMC from January 1991 to December 1993. DNA was extracted and subjected to polymerase chain reaction (PCR) analysis using primers that encompassed the bp 609 C to T mutation. Restriction endonuclease cleavage with Hinf 1 and gel electrophoresis were used to determine the polymorphism status of each patient.


RESULTS
DNA of 46 patients was successfully amplified. The 46 patients were distributed as follows: 26 (56.5%) C/C-homozygous wildtype, 18 (39%) T/C-heterozygous, and 2 (4.5%) T/T-homozygous mutant. Eleven of 46 patients had suffered treatment failure. The status of the bp 609 polymorphism in this group was 5 (45.5%) C/C, 5 (45.5%) C/T, and 1 (9%) T/T.


CONCLUSIONS
In this series, there was not an overrepresentation of the mutant allele in patients with treatment failure, suggesting that the bp 609 alteration is not a strong determinant of treatment outcome.
Goldberg
Z I
ZI
Department of Radiation Oncology, Ontario Cancer Institute/Princess Margaret Hospital, Toronto, Canada.
Cummings
B J
BJ
Chapman
W B
WB
Klamut
H J
HJ
Rauth
A M
AM
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001005:Anus Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D016685:Mitomycin / Q000008:administration & dosage; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D016896:Treatment Outcome
D009363:Neoplasm Proteins; D016685:Mitomycin; D016660:NAD(P)H Dehydrogenase (Quinone); D005472:Fluorouracil