NAT2 fast acetylator genotype is associated with an increased risk of colorectal cancer in Taiwan.
In Taiwan, colorectal cancer has one of the highest rates of increased incidence in the past two decades. Heterocyclic amines from dietary cooked meats are metabolically activated by NAT2 (N-acetyltransferase 2), which are associated with colorectal cancer incidence. Thus, the NAT2 fast acetylator genotype may be associated with colorectal cancer risk. However, the association between the NAT2 genotype and colorectal cancer risk is not clearly understood. We conducted a study with 244 primary colorectal cancer cases and 299 cancer-free healthy control subjects to verify the association of NAT2 polymorphisms with the risk of Taiwanese colorectal cancer. Our data showed that subjects with the NAT2 W/W homozygous genotype had a 1.63-fold increased risk of colorectal cancer compared with those with the Mx/Mx slow acetylator genotype (95 percent confidence interval, 1.03-2.58); however, no risk was found in the W/Mx heterozygous and Mx/W+W/W fast acetylator genotypes. Being stratified by gender factors, the colorectal cancer risk in females with homozygous W/W or Mx/W+W/W fast acetylators increased 2.47-fold and 2.13-fold compared with those with the Mx/Mx slow acetylator genotype (95 percent confidence interval, 1.27-4.82 for W/W genotype; 95 percent confidence interval, 1.17-3.89 for Mx/W+W/W genotype); however, the risk of the NAT2 genotype and colorectal cancer was not observed in males. 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.
Huang
Chi-Chou
CC
Colorectal Division, Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan, Republic of China.
Chien
Wen-Pin
WP
Wong
Ruey-Hong
RH
Cheng
Ya-Wen
YW
Chen
Meng-Cheng
MC
Chou
Ming-Chih
MC
Lee
Huei
H
D000368:Aged; D000483:Alleles; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D012307:Risk Factors; D017678:Sex Distribution; D012737:Sex Factors; D013624:Taiwan / Q000453:epidemiology
D004273:DNA, Neoplasm; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human