N-acetyltransferase (NAT1, NAT2) and glutathione S-transferase (GSTM1, GSTT1) polymorphisms in breast cancer.
To evaluate the potential association between NAT1/NAT2 polymorphisms and breast cancer, a case-control study was conducted in Korean women (254 cases, 301 controls). NAT1 *4/*10 genotype (42%) was the most common NAT1 genotype in this Korean population. The frequencies of slow, intermediate and rapid NAT2 acetylator genotype were 16, 39 and 44% in cases and 16, 42 and 42% in controls. Neither NAT1 rapid (homozygous or heterozygous NAT1 *10) (OR=1.2, 95% CI=0.8-1.9) nor NAT2 rapid acetylator genotype (OR=1.2, 95% CI=0.8-1.7) showed significant association with breast cancer risk. Although the risk of NAT2 rapid acetylator genotype in postmenopausal women (OR=1.4, 95% CI=0.7-2.8) was higher than that in premenopausal women (OR=1.1, 95% CI=0.7-1.7), those were not statistically significant. However, combinations of NAT1, GSTM1 and GSTT1 genotypes showed a significant linear gene-dosage relationship with breast cancer (p for trend=0.04) and those women with NAT2 rapid acetylator and both GSTM1 and GSTT1 null genotypes were at the elevated risk (OR=3.1, 95% CI=1.0-9.1). These results suggest that genetic polymorphisms of NAT1 and NAT2 have no independent effect on breast cancer risk, but they modulate breast cancer risk in the presence of GSTM1 and GSTT1 null genotypes.
Lee
Kyoung-Mu
KM
Department of Preventive Medicine, Seoul National University College of Medicine, Cancer Research Institute, 28 Yongon-Dong, Chongno-Gu, Seoul 110-799, South Korea.
Park
Sue-Kyung
SK
Kim
Sook-Un
SU
Doll
Mark A
MA
Yoo
Keun-Young
KY
Ahn
Sei-Hyun
SH
Noh
Dong-Young
DY
Hirvonen
Ari
A
Hein
David W
DW
Kang
Daehee
D
D000123:Acetyltransferases / Q000235:genetics*; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes; D008875:Middle Aged; D011110:Polymorphism, Genetic
D000123:Acetyltransferases; D001191:Arylamine N-Acetyltransferase; D005982:Glutathione Transferase; D007527:Isoenzymes; C089384:N-acetyltransferase 1; C478900:NAT2 protein, human; C413545:glutathione S-transferase T1