Abstract
Background
Recent studies have suggested that the association between smoking and breast cancer risk might be modified by polymorphisms in the N-acetyltransferase 2 gene (NAT2). Most of these studies were conducted in Western countries, with few reports from East Asia.
Methods
We conducted a case–control study of 511 breast cancer cases and 527 unmatched healthy controls from December 2010 to November 2011 in Japan. Unconditional logistic regression was used to analyze the association of smoking with breast cancer risk stratified by NAT2 phenotype.
Results
In this population, 11 % of the cases and 10 % of the controls were classified as a slow acetylator phenotype. Compared to never smokers, current smokers had an increased breast cancer risk in multivariate analysis [odds ratio (OR) = 2.27, 95 % confidence interval (95 %CI) = 1.38–3.82]. Subgroup analyses of menopausal status indicated the same tendency. Subgroup analyses of NAT2 phenotype, the ORs in both of rapid and slow acetylator phenotype subgroups were comparable, and no interactions were observed between smoking status and NAT2 phenotype (p = 0.97). A dose-dependent effect of smoking on breast cancer risk was seen for the rapid acetylator phenotype, but not for the slow acetylator phenotype.
Conclusion
Given the high frequency of the rapid acetylator phenotype, these results show that smoking is a risk factor for breast cancer among most Japanese women. It may be of little significance to identify the NAT2 phenotype in the Japanese population.
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References
International Agency for Research on Cancer. Personal habits and indoor combustions. IARC monographs on the evaluation of carcinogenic risks to humans, vol 100E. Lyon: International Agency for Research on Cancer; 2012. pp. 93.
Ambrosone CB, Kropp S, Yang J, Yao S, Shields PG, Chang-Claude J. Cigarette smoking, N-acetyltransferase 2 genotypes, and breast cancer risk: pooled analysis and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2008;17:15–26.
Cox DG, Dostal L, Hunter DJ, Marchand LL, Hoover R, Ziegler RG, et al. N-acetyltransferase 2 polymorphisms, tobacco smoking and breast cancer in the breast and prostate cancer cohort consortium. Am J Epidemiol. 2011;174:1316–22.
Kurose K, Sugiyama E, Saito Y. Population differences in major functional polymorphisms of pharmacokinetics/pharmacodynamics-related genes in Eastern Asians and Europeans: implications in the clinical trials for novel drug development. Drug Metab Pharmacokin. 2012;27:9–54.
Sabbagh A, Langaney A, Darlu P, Gerard N, Krishnamoorthy R, Poloni ES. Worldwide distribution of NAT2 diversity: implications for NAT2 evolutionary history. BMC Genet. 2008;9:21.
Ambrosone CB, Freudenheim JL, Graham S, Marshall JR, Vena JE, Brasure JR, et al. Cigarette smoking, N-acetyltransferase 2 genetic polymorphisms, and breast cancer risk. JAMA. 1996;276:1494–501.
Hunter DJ, Hankinson SE, Hough H, Gertig DM, Garcia-Closas M, Spiegelman D, et al. A prospective study of NAT2 acetylation genotype, cigarette smoking, and risk of breast cancer. Carcinogenesis. 1997;18:2127–32.
Millikan RC, Pittman GS, Newman B, Tse CJ, Selmin O, Rockhill B, et al. Cigarette smoking, N-acetyltransferases 1 and 2, and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 1998;7:371–8.
Morabia A, Bernstein MS, Bouchardy I, Kurtz J, Morris MA. Breast cancer and active and passive smoking: the role of the N-acetyltransferase 2 genotype. Am J Epidemiol. 2000;152:226–32.
Krajinovic M, Ghadirian P, Richer C, Sinnett H, Gandini S, Perret C, et al. Genetic susceptibility to breast cancer in french-canadians: role of carcinogen-metabolizing enzymes and gene-environment interactions. Int J Cancer. 2001;92:220–5.
Chang-Claude J, Kropp S, Jager B, Bartsch H, Risch A. Differential effect of NAT2 on the association between active and passive smoke exposure and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2002;11:698–704.
van der Hel OL, Bueno-de-Mesquita HB, van Gils CH, Roest M, Slothouber B, Grobbee DE, et al. Cumulative genetic defects in carcinogen metabolism may increase breast cancer risk (the netherlands). Cancer Causes Control. 2005;16:675–81.
Alberg AJ, Daudt A, Huang H, Hoffman SC, Comstock GW, Helzlsouer KJ, et al. N-acetyltransferase 2 (NAT2) genotypes, cigarette smoking, and the risk of breast cancer. Cancer Detect Prev. 2004;28:187–93.
Sillanpaa P, Hirvonen A, Kataja V, Eskelinen M, Kosma V, Uusitupa M, et al. NAT2 slow acetylator genotype as an important modifier of breast cancer risk. Int J Cancer. 2005;114:579–84.
Lissowska J, Brinton LA, Zatonski W, Blair A, Bardin-Mikolajczak A, Peplonska B, et al. Tobacco smoking, NAT2 acetylation genotype and breast cancer risk. Int J Cancer. 2006;119:1961–9.
Annual report of breast cancer screening rates. Ministry of Health, Labour and Welfare (MHLW). http://www.mhlw.go.jp/stf/houdou/2r9852000001igt0-att/2r9852000001iguh.pdf. Accessed 19 Jan 2016.
Nagata C, Mizoue T, Tanaka K, Tsuji I, Wakai K, Inoue M, et al. Tobacco smoking and breast cancer risk: an evaluation based on a systematic review of epidemiological evidence in the Japanese population. Jpn J Clin Oncol. 2006;36:387–94.
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Funding
This study was supported by a Grant-in-Aid for Scientific Research (C) (15K08713) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
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Hara, A., Taira, N., Mizoo, T. et al. N-acetyltransferase 2 polymorphism and breast cancer risk with smoking: a case control study in Japanese women. Breast Cancer 24, 254–262 (2017). https://doi.org/10.1007/s12282-016-0696-1
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DOI: https://doi.org/10.1007/s12282-016-0696-1