title: N-acetyltransferase 2 genotype modification of active cigarette smoking on breast cancer risk among hispanic and non-hispanic white women.
abstract: While it has been demonstrated that cigarette smoke contains aromatic and heterocyclic amines that initiate carcinogenesis, the association between cigarette smoking and breast cancer remains controversial. N-acetyltransferase 2 (NAT2) catalyzes arylamine carcinogen biotransformation and NAT2 genetic polymorphisms may contribute to differential susceptibility to breast cancer. We tested whether NAT2 modified the association between cigarette smoking and breast cancer risk in a population-based study of Hispanic and non-Hispanic white women in the Southwest United States. Data were available for cigarette smoking and NAT2 polymorphisms for 717 cases (Hispanic, 251 and non-Hispanic white, 466) and 735 controls (Hispanic, 245 and non-Hispanic white, 490). NAT2 genotypes were translated into rapid, intermediate, slow, or very slow acetylator phenotypes. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for the joint association of NAT2 with smoking on breast cancer risk were estimated using logistic regression. Non-Hispanic white women were more likely (p < 0.001) than Hispanic women to have a slow (41.7 vs. 33.5%) or very slow (19.0 vs. 11.1%) acetylator status and less likely to have rapid/intermediate phenotypes (39.2 vs. 54.4%). Breast cancer risk was significantly increased in non-Hispanic white women with a very slow acetylator phenotype who smoked: ever versus never (OR, 2.57; 95% CI, 1.49-4.41), never versus former (OR, 2.69; 95% CI, 1.41-5.17) or current (OR, 2.46; 95% CI, 1.07-5.65), and 16 + pack-years (OR, 2.29; 95% CI, 1.16-4.51). Results for Hispanic women were not statistically significant. These findings support smoking as a risk factor for breast cancer among non-Hispanic white women with very slow NAT2 acetylator phenotype.
authors.affiliation: Department of Epidemiology & Population Health, University of Louisville, Louisville, Kentucky 40292, USA.
authors.forename: Kathy B
authors.initials: KB
authors.lastname: Baumgartner
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Schlierf
authors.forename: Dongyan
authors.initials: D
authors.lastname: Yang
authors.forename: Mark A
authors.initials: MA
authors.lastname: Doll
authors.forename: David W
authors.initials: DW
authors.lastname: Hein
mesh_terms: D000328:Adult; D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D001943:Breast Neoplasms / Q000201:enzymology*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006630:Hispanic or Latino; D006801:Humans; D008875:Middle Aged; D012307:Risk Factors; D012907:Smoking; D014026:Nicotiana; D044465:White People
chemical_list: D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human
references.citation: J Natl Cancer Inst. 2000 Jul 19;92(14):1151-8
references.pmid: 10904088
references.citation: Vital Health Stat 2. 1993 Dec;(119):1-75
references.pmid: 8135023
references.citation: Carcinogenesis. 1997 Nov;18(11):2127-32
references.pmid: 9395212
references.citation: Am J Epidemiol. 2007 Aug 1;166(3):246-54
references.pmid: 17535831
references.citation: Am J Epidemiol. 1983 Jan;117(1):27-34
references.pmid: 6823950
references.citation: Jpn J Clin Oncol. 2006 Jun;36(6):387-94
references.pmid: 16766567
references.citation: Curr Drug Metab. 2008 Jul;9(6):471-86
references.pmid: 18680467
references.citation: Expert Opin Drug Metab Toxicol. 2009 Apr;5(4):353-66
references.pmid: 19379125
references.citation: J Natl Cancer Inst. 2004 Jan 7;96(1):29-37
references.pmid: 14709736
references.citation: Cancer Causes Control. 2005 Mar;16(2):115-23
references.pmid: 15868453
references.citation: Cancer Epidemiol Biomarkers Prev. 2002 Aug;11(8):698-704
references.pmid: 12163321
references.citation: Cancer Epidemiol Biomarkers Prev. 2005 Jan;14(1):61-6
references.pmid: 15668477
references.citation: Pharmacogenetics. 2004 Nov;14(11):717-23
references.pmid: 15564878
references.citation: Pharmacogenetics. 2000 Jul;10(5):461-9
references.pmid: 10898115
references.citation: Pharmacogenetics. 2001 Apr;11(3):207-15
references.pmid: 11337936
references.citation: Med Sci Sports Exerc. 2006 Jan;38(1):33-41
references.pmid: 16394951
references.citation: Cancer Epidemiol Biomarkers Prev. 2008 Jan;17(1):1-2
references.pmid: 18187387
references.citation: Am J Epidemiol. 2000 Aug 1;152(3):226-32
references.pmid: 10933269
references.citation: Pharmacogenetics. 2003 Jul;13(7):399-407
references.pmid: 12835615
references.citation: Cancer Causes Control. 2003 Feb;14(1):43-51
references.pmid: 12708724
references.citation: Anal Biochem. 2001 Jan 1;288(1):106-8
references.pmid: 11141315
references.citation: Cancer Detect Prev. 2004;28(3):187-93
references.pmid: 15225898
references.citation: Cancer Res. 1995 Aug 15;55(16):3531-6
references.pmid: 7627960
references.citation: Curr Drug Metab. 2008 Jul;9(6):487-97
references.pmid: 18680468
references.citation: Cancer Epidemiol Biomarkers Prev. 1998 May;7(5):371-8
references.pmid: 9610785
references.citation: Rev Environ Health. 2001 Jul-Sep;16(4):253-61
references.pmid: 12041881
references.citation: JAMA. 1996 Nov 13;276(18):1494-501
references.pmid: 8903261
references.citation: Curr Med Chem Cardiovasc Hematol Agents. 2005 Jan;3(1):45-54
references.pmid: 15638743
references.citation: Cancer Epidemiol Biomarkers Prev. 1995 Apr-May;4(3):233-8
references.pmid: 7606197
references.citation: Int J Cancer. 2001 Apr 15;92(2):220-5
references.pmid: 11291049
references.citation: Carcinogenesis. 2003 Apr;24(4):719-25
references.pmid: 12727801
references.citation: Mutat Res. 2002 Sep 30;506-507:65-77
references.pmid: 12351146
references.citation: Cancer Epidemiol Biomarkers Prev. 2008 Jan;17(1):15-26
references.pmid: 18187392
references.citation: Cancer Epidemiol Biomarkers Prev. 2004 Sep;13(9):1543-6
references.pmid: 15342459
references.citation: Cancer Epidemiol Biomarkers Prev. 2002 Oct;11(10 Pt 1):953-71
references.pmid: 12376493
references.citation: Breast Cancer Res Treat. 2007 Mar;102(1):85-101
references.pmid: 17080310
references.citation: Int J Cancer. 1999 Jul 19;82(2):175-9
references.pmid: 10389748
references.citation: Carcinogenesis. 2002 Feb;23(2):301-6
references.pmid: 11872636
references.citation: Carcinogenesis. 2007 Aug;28(8):1665-71
references.pmid: 17434923
references.citation: Am J Epidemiol. 2007 Nov 15;166(10):1210-9
references.pmid: 17827445
references.citation: Oncogene. 2006 Mar 13;25(11):1649-58
references.pmid: 16550165
references.citation: Mutat Res. 2009 Dec 1;671(1-2):13-9
references.pmid: 19682468
references.citation: Chem Res Toxicol. 1992 Sep-Oct;5(5):585-90
references.pmid: 1445997
references.citation: J Epidemiol. 2008;18(2):77-83
references.pmid: 18403857
references.citation: Breast Cancer Res. 2005;7(3):R385-93
references.pmid: 15987434
references.citation: Int J Cancer. 2006 Oct 15;119(8):1961-9
references.pmid: 16721725
references.citation: Breast Cancer Res Treat. 2008 May;109(1):101-11
references.pmid: 17594514
references.citation: Breast Cancer Res Treat. 2009 Mar;114(1):137-45
references.pmid: 18670874
references.citation: Methods Mol Biol. 2009;471:3-29
references.pmid: 19109772
references.citation: Ethn Dis. 2002 Fall;12(4):460-9
references.pmid: 12477131
references.citation: Minerva Ginecol. 2004 Feb;56(1):105-14
references.pmid: 14973414
references.citation: Hum Mol Genet. 1994 May;3(5):729-34
references.pmid: 8081359
references.citation: Int J Cancer. 2005 Apr 20;114(4):579-84
references.pmid: 15609332