Thymidylate synthase gene polymorphism as a prognostic factor for colon cancer.
The human thymidylate synthase (TS) gene promoter is polymorphic, having either double or triple tandem repeats of a 28-base-pair (bp) sequence. Here, we determined the significance of this polymorphism in predicting the clinical outcomes for patients with colon cancer. We reviewed 121 consecutive patients with stage II or III colon cancer who underwent a curative resection. After DNA extraction from paraffin-embedded tissues, the promoter region of the TS gene was amplified by polymerase chain reaction. In addition to the conventional prognostic factors, patient survivals were compared with regard to the pattern of TS polymorphism. Sixty-eight subjects were homozygotes for the triple-repeat variant (250 bp, group A), and 53 subjects (group B) were either homozygotes for the double-repeat variant (220 bp) or heterozygotes (220 and 250 bp). We found a significant difference between groups A and B in survival (53% versus 80%, P=0.0481). The difference was particularly significant in the patients with stage III disease (41% versus 77%, P=0.0414). Tumor stage and the TS polymorphism were identified as significant prognostic factors by multivariate analysis. We found the TS polymorphism to be a significant and independent prognostic factor for colon cancer.
Suh
Kwang Wook
KW
Departments of Surgery, Ajou University School of Medicine, Suwon 442-749, Korea. suhkw@ajou.ac.kr
Kim
Joo Hyung
JH
Kim
Young Bae
YB
Kim
Jeongmi
J
Jeong
Soohyun
S
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000534:rehabilitation; D000368:Aged; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis*; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D003082:Colectomy / Q000379:methods; D003110:Colonic Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D013940:Thymidylate Synthase