NAT2 gene polymorphism and sporadic colorectal cancer. Prevalence, tumor stage and prognosis. A preliminary study in 70 patients.
OBJECTIVE
Theoretically, individuals with a NAT2 rapid acetylator genotype are exposed to a higher risk of developing colorectal cancer. We attempted to study this relationship.


METHODS
We evaluated a group of 70 patients with sporadic colorectal cancer and 40 controls. We calculated the relative risk for patients homozygous for the normal allele NAT2*5C, NAT2*5A, NAT2*6B, NAT2*7B, for heterozygous patients and for patients homozygous for the mutant allele.


RESULTS
We found an increased risk for patients with a rapid acetylator genotype to develop colorectal cancer. Rapid acetylators, homozygous negative or heterozygous for the NAT2*5C, NAT2*5A and NAT2*6B mutations have an increased risk of colorectal cancer compared to homozygous positive patients.The analysis of the NAT2*5C genotype shows that the majority of the cases are at stage pT3 for rapid acetylators, 41 cases (74.54%), compared to slow acetylators, where the majority of cases are at stage pT4, 10 cases (66.66%) (p<0.05). The genotype with a rapid acetylator phenotype of the NAT2*5C, NAT2*5A and NAT2*7B variants was most frequently associated with Dukes stage B. The NAT2*5C, NAT2*5A and NAT2*7B gene variants with a slow acetylator pheno-type were most frequently associated with Dukes stage C.


CONCLUSIONS
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. Rapid acetylators have earlier stages of colorectal cancer and a better prognosis than slow acetylators, who are diagnosed in more advanced stages.
Osian
Gelu
G
3rd Surgical Clinic, University of Medicine and Pharmacy Cluj-Napoca, Romania. geluosian@yahoo.com
Procopciuc
Lucia
L
Vlad
Liviu
L
D000107:Acetylation; D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D010641:Phenotype; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D012383:Romania / Q000453:epidemiology
D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human