Possible influence of glutathione S-transferase GSTT1 null genotype on age of onset of sporadic colorectal adenocarcinoma.
BACKGROUND
Glutathione S-transferase enzymes mediate exposure to cytotoxic and genotoxic agents and may be involved in cancer susceptibility. Both glutathione S-transferase mu 1 (GSTM1) and GST theta 1 (GSTT1) genes have a null variant allele in which the entire gene is absent. The association of glutathione S-transferase null genotype and risk of developing colorectal cancer is not yet fully clarified.


METHODS
We tested whether the null genotypes for GSTM1 and GSTT1 genes altered the risk for sporadic colorectal adenocarcinoma in Brazilian patients. Genomic DNA from 102 sporadic colorectal adenocarcinoma patients and 300 controls was analyzed by polymerase chain reaction.


RESULTS
Frequencies of GSTM1, GSTT1, and null combined genotypes were similar in patients and controls (49.9 vs. 44.6 percent, 16.6 vs. 17.3 percent, and 8.8 vs. 8 percent, respectively). We found a 1.03-fold (95 percent confidence interval, 0.96-1.10) and 1.08-fold (95 percent confidence interval, 0.99-1.18) increased risk associated with GSTM1 and GSTT1 null genotypes, respectively (P = 0.45 and P = 0.08) and a 1.18-fold (95 percent confidence interval, 0.47-2.90) increased risk associated with the combined null genotype (P = 0.74). The GSTT1 null genotype was more common in patients who were diagnosed before the age of 60 years than in those who were diagnosed at an older age (28.8 vs. 4 percent, respectively; P = 0.0008).


CONCLUSIONS
The results suggest that inherited absence of this carcinogen detoxification pathway may not be associated with sporadic colorectal adenocarcinoma in the present cases. However, a higher frequency of GSTT1 null genotype in patients diagnosed before the age of 60 years suggests that this genotype could influence the age of disease onset in Brazil.
Nascimento
Helvia
H
Department of Internal Medicine, State University of Campinas, Campinas, São Paulo, Brazil.
Coy
Claudio S R
CS
Teori
Maria T
MT
Boin
Ilka F S F
IF
Góes
Juvenal R N
JR
Costa
Fernando F
FF
Lima
Carmen S P
CS
D000230:Adenocarcinoma / Q000453:epidemiology* / Q000235:genetics*; D017668:Age of Onset; D001938:Brazil / Q000453:epidemiology; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016036:Seroepidemiologic Studies
D005982:Glutathione Transferase; C413545:glutathione S-transferase T1