title: N-acetyltransferase 2 polymorphisms, tobacco smoking, and breast cancer risk in the breast and prostate cancer cohort consortium.
abstract: Common polymorphisms in the N-acetyltransferase 2 gene (NAT2) modify the association between cigarette smoking and bladder cancer and have been hypothesized to determine whether active cigarette smoking increases breast cancer risk. The authors sought to replicate the latter hypothesis in a prospective analysis of 6,900 breast cancer cases and 9,903 matched controls drawn from 6 cohorts (1989-2006) in the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium. Standardized methods were used to genotype the 3 most common polymorphisms that define NAT2 acetylation phenotype (rs1799930, rs1799931, and rs1801280). In unconditional logistic regression analyses, breast cancer risk was higher in women with more than 20 pack-years of active cigarette smoking than in never smokers (odds ratio (OR) = 1.28, 95% confidence interval (CI): 1.17, 1.39), after controlling for established risk factors other than alcohol consumption and physical inactivity. However, associations were similar for the slow (OR = 1.25, 95% CI: 1.11, 1.39) and rapid/intermediate (OR = 1.24, 95% CI: 1.08, 1.42) acetylation phenotypes, with no evidence of interaction (P = 0.87). These results provide some support for the hypothesis that long-term cigarette smoking may be causally associated with breast cancer risk but underscore the need for caution when interpreting sparse data on gene-environment interactions.
authors.affiliation: Lyon Cancer Research Center, Centre Le´on Be´ rard, France. david.cox@lyon.unicancer.fr
authors.forename: David G
authors.initials: DG
authors.lastname: Cox
authors.forename: Lucie
authors.initials: L
authors.lastname: Dostal
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Robert
authors.initials: R
authors.lastname: Hoover
authors.forename: Regina G
authors.initials: RG
authors.lastname: Ziegler
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Thun
mesh_terms: D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008593:Menopause; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
chemical_list: D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human
references.citation: Mutat Res. 2005 Mar 7;581(1-2):97-104
references.pmid: 15725609
references.citation: Nat Rev Cancer. 2005 Dec;5(12):977-85
references.pmid: 16341085
references.citation: Nat Genet. 2008 May;40(5):616-22
references.pmid: 18385676
references.citation: IARC Monogr Eval Carcinog Risks Hum. 2004;83:1-1438
references.pmid: 15285078
references.citation: Lancet Oncol. 2009 Nov;10(11):1033-4
references.pmid: 19891056
references.citation: Cancer Epidemiol Biomarkers Prev. 2008 Jan;17(1):15-26
references.pmid: 18187392
references.citation: Bioinformatics. 2009 May 1;25(9):1185-6
references.pmid: 19261719
references.citation: Cancer Res. 2009 Aug 15;69(16):6633-41
references.pmid: 19654303
references.citation: Br J Cancer. 2002 Nov 18;87(11):1234-45
references.pmid: 12439712
references.citation: Int J Cancer. 2004 Jul 1;110(4):598-604
references.pmid: 15122594
references.citation: Biomed Environ Sci. 2004 Sep;17(3):291-8
references.pmid: 15602826
references.citation: Tob Control. 2011 Jan;20(1):e2
references.pmid: 21148114
references.citation: Curr Opin Urol. 2009 Sep;19(5):494-9
references.pmid: 19553820
references.citation: Int J Epidemiol. 2007 Feb;36(1):236-41
references.pmid: 17510079
references.citation: Stat Med. 2002 Jan 15;21(1):35-50
references.pmid: 11782049