title: NAT2 slow acetylator genotype as an important modifier of breast cancer risk.
abstract: N-acetyltransferase 2 (NAT2) is a polymorphic enzyme participating in the metabolism of numerous pharmaceutical drugs and carcinogens found in tobacco smoke and diet. The NAT2 gene is highly polymorphic and several different allelic variants exist that determine the acetylator phenotype. In the course of our case-control study, we developed a new method based on fluorogenic allele-specific probes for analyzing the C282T and T341C polymorphisms of the NAT2 gene in 483 Finnish breast cancer patients and 482 healthy population controls. The slow NAT2 acetylation capacity-associated genotypes posed a somewhat increased overall breast cancer risk (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.01-1.73). This association was found to be confined to the advanced (stage III or IV) breast cancer (OR, 2.60; 95% CI, 1.29-5.24). When stratified by smoking habits, women who had smoked <5 pack-years and carried a NAT2 slow acetylator genotype were at a 2.6-fold (OR, 2.55; 95% CI, 1.01-6.48) risk of breast cancer. Moreover, women with the NAT2 slow acetylator genotype and low body mass index (BMI) (<25.4 kg/m2) were at somewhat increased risk of this malignancy (OR, 1.60; 95% CI, 1.07-2.39). Our results therefore suggest that NAT2 slow acetylator genotype may be an important modifier of environmentally induced breast cancer risk in Finnish women.
authors.affiliation: Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Pia
authors.initials: P
authors.lastname: Sillanpää
authors.forename: Ari
authors.initials: A
authors.lastname: Hirvonen
authors.forename: Vesa
authors.initials: V
authors.lastname: Kataja
authors.forename: Matti
authors.initials: M
authors.lastname: Eskelinen
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Kosma
authors.forename: Matti
authors.initials: M
authors.lastname: Uusitupa
authors.forename: Harri
authors.initials: H
authors.lastname: Vainio
authors.forename: Katja
authors.initials: K
authors.lastname: Mitrunen
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D001943:Breast Neoplasms / Q000209:etiology* / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D017931:DNA Primers / Q000737:chemistry; D004777:Environment; D005260:Female; D005387:Finland; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008572:Menarche; D008593:Menopause; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012306:Risk; D012907:Smoking; D013997:Time Factors
chemical_list: D017931:DNA Primers; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase