The results are illustrated through a twin study for genetic heritability and a meta-analysis for the association between the N-acetyltransferase 2 (NAT2) acetylation status and colorectal cancer.
The combination of GSTM1-null/NAT2 rapid acetylator phenotype/smoking behavior or GSTM1-null/NAT2 rapid acetylator phenotype/diet rich in fried red meat was not found to influence the sporadic CRC risk in Romanians, but the GSTM1-null genotype, NAT2 rapid acetylator phenotype influenced the sporadic CRC risk differently depending on the gender of the patient.
We selected five candidate polymorphisms in following genes: ERCC1 Asp118Asn (rs11615), XPC i11C/A (rs2279017), XRCC3 rs861539" genes_norm="7517">Met241Thr (rs861539) CYP1A1 rs1048943" genes_norm="1543">Ile462Val (rs1048943) and NAT2A803G (rs1208) and assessed the importance of chosen SNPs on groups consisting of 478 CRC patients and 404 controls.
High coffee and tea consuming subjects with slow CYP1A2 or NAT2 activity had a similar CRC risk compared to non/low coffee and tea consuming subjects with a fast CYP1A2 or NAT2 activity, which suggests that caffeine metabolism does not affect the link between coffee and tea consumption and CRC risk.
We conducted a family-based case-control study to investigate the association between polymorphisms in carcinogen metabolism genes (CYP1A2 -154A>C, CYP1B1 Leu432Val, CYP2E1 -1054C>T, GSTP1 Ile105Val, PTGS2 5UTR -765, EPHX1 Tyr113His, NAT2 Ile114Thr, NAT2Arg197Gln and NAT2Gly286Glu) and CRC risk.
No significantly elevated CRC risk in individuals with NAT2 slow acetylators compared with fast acetylators was found when all studies pooled (OR = 0.95, 95% CI: 0.87-1.04, I(2) = 52.6%).
Correlations between NAT2*5C(T341C), NAT2*5A(C481T), NAT2*6B(G590A), NAT2*7B(G857A) polymorphisms and survival of patients with different Dukes-MAC stages of CRC were analyzed.
We investigated the modifying effects of NAT1 and NAT2 polymorphisms on the association of meat consumption, heterocyclic amine intake, and smoking with colorectal cancer risk.
Although variant alleles of CYP1A2 were associated with colorectal cancer (OR = 0.27; 95% CI = 0.07-0.99), genetic polymorphisms of NAT2, CYP1A1, and CYP1A2 did not influence the association of HCA intake with colorectal cancer.
A hospital-based study was designed to investigate the association between colorectal cancer and cytochrome P-450 1A2, N-acetyltransferase 1, and N-acetyltransferase 2, with the interaction of meat consumption.
These results also indicate that the NAT2 in combination with CYP1A1*2C, CYP1A2*1C, or GSTM1 genotypes may strongly confer susceptibility to colorectal cancer.
Collectively, patients with the NAT2 fast acetylator genotype were more prone to colorectal cancer and reflected the possibility that exposure to heterocyclic amines may contribute to colorectal cancer development in Taiwan, especially in Taiwanese females.
To clarify the potential modifying role of the NAT2 acetylator status in microsatellite stable (MSS) colorectal cancer (CRC), we studied 140 patients with sporadic CRC (group 1) and 69 patients with CRC who met at least one criterion of the revised Bethesda guidelines (group 2).
Rapid acetylators, homozygous negative or heterozygous for the NAT2*5C, NAT2*5A and NAT2*6B mutations have a higher risk of colorectal cancer compared to positive homozygotes.
These data suggest that, in combination with meat intake, some proportion of the international variability in CRC incidence may be attributable to genetic susceptibility to heterocyclic amines, as determined by NAT2 genotype.
Although only NAT2*14A fast type was associated with increased risk in patients with colorectal carcinoma (OR = 3.03; 95% CI, 1.56-5.86), when a high protein diet was considered, NAT2*7A/B fast genotype was also found to be associated with an increased risk (OR = 2.06, 95% CI for NAT2*7A/B, 1.10-3.86; OR = 2.65; 95% CI, 1.29-5.46 for NAT2*14A).
Our findings indicate that NAT1 and NAT2 genotypes may contribute jointly to individual susceptibility and that heterocyclic aromatic amines may play an important role in colorectal cancer associated with red meat and possibly also exposure to environmental tobacco smoke.
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.