Breast Cancer

, Volume 25, Issue 2, pp 176–184 | Cite as

Passive smoking, NAT2 polymorphism, and breast cancer risk in Israeli Arab women: a case–control study

  • Z. Regev-Avraham
  • O. Baron-Epel
  • S. K. Hammond
  • L. Keinan-Boker
Original Article



The effect of passive smoking (PS) on breast cancer (BC) is controversial, and may be modified by polymorphism of the N-Acetyl-transferase (NAT) 2 enzyme which is involved in tobacco carcinogen metabolism. We aimed to evaluate the relationship between PS and BC by NAT2 variants in Arab–Israeli women, a unique population with low active smoking rates, and high exposure to PS.


A population-based case-control study was carried out on non-smoking 137 prevalent breast cancer patients and 274 population-based controls, aged 30–70 years. Data on past and current PS, sociodemographic, and other characteristics were retrieved through interviews, and buccal smears were provided for NAT2 analyses. Logistic regression models adjusting for potential confounders assessed the odds ratios (ORs) and 95% confidence intervals (95% CI) of the association between PS and BC.


Ever PS was associated with increased BC risk: OR = 2.22, 95% CI 1.28–3.87. Higher lifetime PS exposure was associated with higher BC risk: Compared to never exposed women, women exposed to PS most of their lives had a threefold higher BC risk (OR = 3.16, 95% CI 1.70–5.87, P trend < 0.001). NAT2 polymorphism did not modify these associations.


PS exposure in non-smoking Israeli Arab women is significantly associated with increased risk for BC, potentially allowing for specific intervention; NAT2 polymorphism does not modify this association.


Arab Breast cancer Case–control NAT2 Passive smoking 



The authors of this study acknowledge and thank the Israeli Arabic women of northern Israel who participated in this study. We would also like to thank Prof Zidan of Ziv Medical Center in Zefat and Dr. Hadassah Goldberg of West Galilee Medical Center in Nahariya for their cooperation and help in conducting the study.The study was conducted as partial fulfillment of the requirements for a Ph.D. degree of Z. Regev-Avraham at the University of Haifa.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.


  1. 1.
    Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: Accessed 21 June 2017.
  2. 2.
    Israel National Cancer Registry, Ministry of Health. Available at: Accessed 21 June 2017.
  3. 3.
    Beaber EF, Buist DS, Barlow WE, Malone KE, Reed SD, Li CI. Recent oral contraceptive use by formulation and breast cancer risk among women 20–49 years of age. Cancer. 2014;74(15):4078–89.Google Scholar
  4. 4.
    Zbuk K, Anand SS. Declining incidence of breast cancer after decreased use of hormone-replacement therapy: magnitude and time lags in different countries. J Epidemiol Community Health. 2012;66(1):1–7.CrossRefPubMedGoogle Scholar
  5. 5.
    Pettersson A, Graff RE, Ursin G, Santos-Silva ID, McCormack V, Baglietto L et al. Mammographic density phenotypes and risk of breast cancer: a meta-analysis. J Natl Cancer Inst 2014;106(5).Google Scholar
  6. 6.
    Boyle P, Levin B. International Agency for Research on Cancer. IARC monographs on the evaluation of carcinogenic risks to humans’ tobacco smoke and in voluntary smoking. 83 vol. Lyon: World Health Organization; 2008.Google Scholar
  7. 7.
    Johnson KC. Accumulating evidence on passive and active smoking and breast cancer risk. Int J Cancer. 2005;117(4):619–28.CrossRefPubMedGoogle Scholar
  8. 8.
    Johnson KC, Miller AB, Collishaw NE, Pamer JR, Hammond SK, Salom AG, et al. Active smoking and secondhand smoke increase breast cancer risk: the report of the Canadian Expert Panel on Tobacco Smoke and Breast Cancer Risk. Tob Control. 2011;20:e2.CrossRefPubMedGoogle Scholar
  9. 9.
    Reynolds P. Smoking and breast cancer. J Mammary Gland Biol Neoplasia. 2013;18(1):15–23.CrossRefPubMedGoogle Scholar
  10. 10.
    Hecht S. Tobacco smoke carcinogens and breast cancer. Environ Mol Mutagen. 2002;39:119–26.CrossRefPubMedGoogle Scholar
  11. 11.
    Chen C, Huang YB, Liu XB, Gao Y, Dai HJ, Song FJ, et al. Active and second hand smoking with breast cancer risk for Chinese females: a systematic review and meta-analysis. Chin J Cancer. 2014;33(6):306–16.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Dossus L, Boutron-Ruault MC, Kaaks R, Gram IT, Vilier A, Fervers B, et al. Active and passive cigarette smoking and breast cancer risk: results from the EPIC cohort. Int J Cancer. 2014;134(8):1871–88.CrossRefPubMedGoogle Scholar
  13. 13.
    Gao CM, Ding JH, Li SP, Liu YT, Qian Y, Chang J, et al. Active and second hand smoking, and alcohol drinking and breast cancer risk in Chinese women. Asian Pac J Cancer Prev. 2013;14(2):993–6.CrossRefPubMedGoogle Scholar
  14. 14.
    Anderson LN, Cotterchio M, Mirea L, Ozcelik H, Kreiger N. Passive cigarette smoke exposure during various periods of life, genetic variants, and breast cancer risk among never smokers. Am J Epidemiol. 2012;175(4):289–301.CrossRefPubMedGoogle Scholar
  15. 15.
    Boukouvala S, Fakis G. Arylamine N-acetyltransferases: what we learn from genes and genomes. Drug Metab Rev. 2005;37:511–64.CrossRefPubMedGoogle Scholar
  16. 16.
    Cascorbi I, Drakoulis N, Brockmoller J, Maurer A, Sperling K, Roots I. Arylamine N-acetyltransferase (NAT2) mutations and their allelic linkage in unrelated Caucasian individuals: correlation with phenotypic activity. Am J Hum Genet. 1995;57:581–92.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Baumgartner K, Schlierf T, Yang D, Doll M, Hein D. N-acetyltransferase 2 genotype modification of active cigarette smoking on breast cancer risk among hispanic and non-hispanic white women. Toxicol Sci. 2009;112(1):211–20.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Alberg AJ, Daudt A, Huang HY, 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.CrossRefPubMedGoogle Scholar
  19. 19.
    Gu J, Wu X. Genetic susceptibility to bladder cancer risk and outcome. Per Med. 2011;8(3):365–74.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    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.CrossRefPubMedGoogle Scholar
  21. 21.
    Conlon MS, Johnson KC, Bewick MA, Lafrenie RM, Donner A. Smoking (active and passive), N-acetyltransferase 2, and risk of breast cancer. Cancer Epidemiol. 2010;34(2):142–9.CrossRefPubMedGoogle Scholar
  22. 22.
    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(1):15–26.CrossRefPubMedGoogle Scholar
  23. 23.
    Health status in Israel 2010. Israel center for Disease Control, Israel Ministry of Health. Available at: Accessed 21 June 2017.
  24. 24.
    Ben Noach M, Steinberg DM, Rier DA, Goldsmith R, Shimony T, Rosen LJ. Ethnic differences in patterns of secondhand smoke exposure among adolescents in Israel. Nicotine Tob Res. 2012;14(6):648–56.CrossRefPubMedGoogle Scholar
  25. 25.
    Baron-Epel O, Keinan-Boker L, Weinstein R, Shohat T. Persistent high rates of smoking among Israeli Arab males with concomitant. Isr Med Assoc J. 2010;12(12):732–7.PubMedGoogle Scholar
  26. 26.
    Israel Central Bureau of Statistics website Accessed 21 June 2017.
  27. 27.
    Hammond SK, Leaderer BP. A diffusion monitor to measure exposure to passive smoking. Environ Sci Technol. 1987;21(5):494–7.CrossRefPubMedGoogle Scholar
  28. 28.
    Caka FM, Eatough DJ, Lewis EA, Tang H, Hammond SK, Leaderer BP, et al. An intercomparison of sampling techniques for nicotine in indoor environments. Environ Sci Technol. 1990;24(8):1196–203.CrossRefGoogle Scholar
  29. 29.
    Brian P, Leaderer BP, Hammond SK. Evaluation of vapor-phase nicotine and respirable suspended particle mass as markers for environmental tobacco smoke. Environ Sci Technol. 1991;25(4):770–7.CrossRefGoogle Scholar
  30. 30.
    Hein DW. N-acetyltransferase 2 genetic polymorphism: effects of carcinogen and haplotype on urinary bladder cancer risk. Oncogene. 2006;25:1649–58.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    García-Closas M, Malats N, Silverman D, Docemeci M, Kogevinas M, Hein DW, et al. NAT2 slow acetylation, GSTM1 null genotype, and risk of bladder cancer: results from the Spanish Bladder Cancer Study and meta-analyses. Lancet. 2005;366(9486):649–59.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32. Accessed 24 Oct 2017.
  33. 33.
    Sadri G, Mahjub H. Passive or active smoking, which is more relevant to breast cancer. Saudi Med J. 2007;28(2):254–8.PubMedGoogle Scholar
  34. 34.
    Chen Z, Shao J, Gao X, Li X. Effect of passive smoking on female breast cancer in China: A meta-analysis. Asia Pac J Public Health. 2013;27(2):NP58–64.CrossRefPubMedGoogle Scholar
  35. 35.
    Miller MD, Marty MA, Broadwin R, Jhonson KC, Samon AG, Winder B, et al. The association between exposure to environmental tobacco smoke and breast cancer: a review by the California Environmental Protection Agency. Prev Med. 2007;44(2):93–106.CrossRefPubMedGoogle Scholar
  36. 36.
    Li Q, Hsia J, Yang G. Prevalence of smoking in China in 2010. N Engl J Med. 2011;364(25):2469–70.CrossRefPubMedGoogle Scholar
  37. 37.
    Ahern T, Lash T, Egan K, Baron J. Lifetime tobacco smoke exposure and breast cancer incidence. Cancer Causes Control. 2009;20(10):1837–44.CrossRefPubMedGoogle Scholar
  38. 38.
    Okasha M, McCarron P, Gunnell D, Smith GD. Exposures in childhood, adolescence and early adulthood and breast cancer risk: a systematic review of the literature. Breast Cancer Res Treat. 2003;78(2):223–76.CrossRefPubMedGoogle Scholar
  39. 39.
    Liu L, Wu K, Lin X, Yin Y, Zheng X, Tang X, et al. Passive smoking and other factors at different periods of life and breast cancer risk in Chinese women who have never smoked—a case–control study in Chongqing, People’s Republic of China. Asian Pac J Cancer Prev. 2000;1(2):131–7.PubMedGoogle Scholar
  40. 40.
    Biro FM, Deardorff J. Identifying opportunities for cancer prevention during preadolescence and adolescence: puberty as a window of susceptibility. J Adolesc Health. 2013;52(5 Suppl):S15–20.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Reynolds P, Goldberg D, Hurley S, Nelson DO, Largent J, Henderson KD, et al. Passive smoking and risk of breast cancer in the California Teachers Study. Cancer Epidemiol Biomarkers Prev. 2009;18(12):3389–98.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Cox DG, Dostal L, Hunter DJ, Le Marchand L, Hoover R, Ziegler RG. N-acetyltransferase 2 polymorphisms, tobacco smoking, and breast cancer risk in the breast and prostate cancer cohort consortium. Am J Epidemiol. 2011;174(11):1316–22.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Zhang J, Qiu LX, Wang ZH, Wang JL, He SS, Hu XC. NAT2 polymorphisms combining with smoking associated with breast cancer susceptibility: a meta-analysis. Breast Cancer Res Treat. 2010;123(3):877–83.CrossRefPubMedGoogle Scholar
  44. 44.
    Parkin DM. The fraction of cancer attributable to lifestyle and environmental factors in the UK in 2010. Br J Cancer. 2011;105(Suppl 2):S77–81.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© The Japanese Breast Cancer Society 2017

Authors and Affiliations

  1. 1.School of Public Health, Faculty of Social Welfare and Health SciencesUniversity of HaifaHaifaIsrael
  2. 2.School of Public Health, Environmental Health Sciences DivisionUniversity of CaliforniaBerkeleyUSA
  3. 3.Israel Center for Disease Control, Israel Ministry of Health, Gertner InstituteSheba Medical CenterRamat GanIsrael

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