This suggests that the GSTT1 genotype, and perhaps also the GSTM1 genotype for which a similar, but non-significant effect was seen, might influence the age of onset of colorectal cancer.
Glutathione S-transferase GSTT1 genotypes and susceptibility to cancer: studies of interactions with GSTM1 in lung, oral, gastric and colorectal cancers.
We found no increase in the risk of colorectal cancer for either GSTM1 null [odds ratio (OR) = 1.0; 95% confidence interval (CI), 0.7-1.5] or GSTT1 null (OR = 0.8; 95% CI, 0.5-1.2) genotypes.
Recent studies have provided evidence that the GSTM1 null genotype, i.e. lack of the GSTM1 activity, is associated with an increased susceptibility to lung cancer and colorectal cancer.
The CYP 2E1 c2 allele proved to be in significant association with colorectal cancer (OR: 1.91, 95% CI: 1.05-3.52), the CYP 1A1 Val allele was also overrepresented among colon cancer patients (OR: 1.57, 95% CI: 0.90-2.74), and the frequency of GSTM1 homozygous 0 genotype showed only minor difference (OR: 1.19, 95% CI: 0.75-1.35).
Family history of colorectal cancer, N-acetyltransferase (NAT2), and glutathione-S-transferase (GSTM-1) are studied with Western diet and age at diagnosis.
For tumor protein 53 (TP53), N-acetyl transferase 1 (NAT1), NAT2, glutathione-S transferase Mu (GSTM1), glutathione-S transferase Theta (GSTT1), and glutathione-S transferase Pi (GSTP1) polymorphisms, the best estimates are sufficient to exclude a 1.7-fold increase in risk of colorectal cancer.
On the other hand, the GSTT1 null genotype in gastric cancer and null genotypes of GSTM1 and GSTT1 in colorectal cancer were not statistically significant.
Matched case-control analysis identified alleles associated with higher colorectal cancer risk as carriage of CYP1A1*2C (OR = 2.15, 95% CI 1.36-3.39) and homozygosity for GSTM1*2/*2 (OR = 1.53, 95% CI 1.16-2.02).
Meta analysis of these studies showed that GSTT1 deletion (pooled OR = 1.42), N-acetyltransferase 2 (NAT2)-rapid acetylator phenotype and genotye (pooled OR = 1.08) and NAT2-rapid acetylator phenotype (pooled OR = 1.15) had a significantly increased risk for colorectal cancer (P<0.05), other genotypes like GSTM1 deletion, GSTP1 1le105Val, NAT1*10, NAT2-rapid acetylator genotype CYP1A1 L1e462Val, CYP1A1 MspI*C, MTHFR C677T and MTR A2759G had no significant relationship with colorectal cancer (P>0.05).
The association of risk for colorectal cancer and selected red and white meat mutagen indices and the use of white meat drippings, or fried white meat variables was more evident within select combinations of the CYP1A1 genotype and either the GSTM1 genotype or NAT2 than with the CYP1A1 alone.
The GSTM1 0 allele (OR: 1.48, 95% CI: 1.15-1.92) and rapid acetylator genotypes of NAT2 (OR: 1.52, 95% CI: 1.17-1.98) were associated with an elevated risk No statistically significant correlation between NAT1, GSTT1, GSTP1 genotypes and colorectal cancer was found.
In addition, the frequencies of the GSTM1 and GSTT1 deletion genotypes differed significantly between the cases and controls for current smokers; the GSTT1 null genotype especially is associated with a greater risk of colorectal cancer (OR = 2.44, 95% CI: 1.24-4.81).
In this retrospective cohort, we have investigated associations between common GSTM1, GSTM3 and GSTP1 polymorphisms with factors known to influence clinical out-come and patient survival in colorectal cancer.