Cancer Causes & Control

, Volume 24, Issue 4, pp 629–636

Bleomycin-induced mutagen sensitivity, passive smoking, and risk of breast cancer in Chinese women: a case–control study

  • Mingbai Hu
  • Dingfen Han
  • Shengron Sun
  • Yaqun Yan
  • Jingwei Zhang
  • Yunfeng Zhou
Original paper

Abstract

Background

It is well recognized that genetic variation as well as environmental factors modulates breast cancer risk. Deficiencies in DNA repair capacity are thought to associate with breast cancer risk. The main aim of this study was to use the mutagen sensitivity assay as an indirect measure of DNA repair capacity to assess breast cancer risk and the relationship between passive smoking and breast cancer risk among women in China.

Methods

We carried out a case–control study, involving 196 Chinese patients with breast cancer and 211 controls without the disease and with no history of cancer. We investigated the association between mutagen sensitivity and breast cancer risk using bleomycin as the mutagen. Mutagen sensitivity was measured by quantifying the chromatid breaks induced by mutagens in short-term cultures of peripheral blood lymphocytes. Nonparametric tests and the Fisher’s exact test were used to determine the statistical significance of the crude case–control comparisons, followed by logistic regression to adjust for important covariates.

Results

The mean number of bleomycin-induced breaks per cell was 0.81 for cases compared with 0.73 for the controls (p = 0.016). A greater number of bleomycin-induced chromosomal breaks per cell was associated with an increased risk of breast cancer (adjusted odds ratio of 1.82, p trend <0.01). The association between bleomycin sensitivity and breast cancer risk was greater for women who were exposed to tobacco smoke (passive smokers). The combination of bleomycin sensitivity and exposure to tobacco smoke increased risk further; women passive smokers with high sensitivity to bleomycin had a 2.77-fold increased risk of breast cancer.

Conclusions

Our data indicate that increased bleomycin-induced mutagen sensitivity is significantly associated with an increased risk of breast cancer among Chinese women. Exposure to passive smoke is also associated with increased breast cancer risk, and the correlation is even greater for women with both longer passive exposure to tobacco smoke and high sensitivity to bleomycin.

Keywords

Breast cancer Passive smoke MSA Bleomycin Epidemiology 

References

  1. 1.
    Bray F, McCarron P, Parkin DM (2004) The changing global patterns of female breast cancer incidence and mortality. Breast Cancer Res 6(6):229–239PubMedCrossRefGoogle Scholar
  2. 2.
    Newman B, Mu H, Butler LM et al (1998) Frequency of breast cancer attributable to BRCA1 in a population-based series of American women. JAMA 279(12):915–921PubMedCrossRefGoogle Scholar
  3. 3.
    Turnbull C, Rahman N (2008) Genetic predisposition to breast cancer: past, present, and future. Annu Rev Genomics Hum Genet 9:321–345PubMedCrossRefGoogle Scholar
  4. 4.
    Martin AM, Weber BL (2000) Genetic and hormonal risk factors in breast cancer. J Natl Cancer Inst 92(14):1126–1135PubMedCrossRefGoogle Scholar
  5. 5.
    McPherson K, Steel CM, Dixon JM (2000) ABC of breast diseases. Breast cancer-epidemiology, risk factors, and genetics. BMJ 321(7261):624–628PubMedCrossRefGoogle Scholar
  6. 6.
    Scully R (2000) Role of BRCA gene dysfunction in breast and ovarian cancer predisposition. Breast Cancer Res 2(5):324–330PubMedCrossRefGoogle Scholar
  7. 7.
    Helzlsouer KJ, Harris EL, Parshad R et al (1996) DNA repair proficiency: potential susceptibility factor for breast cancer. J Natl Cancer Inst 88(11):754–755PubMedCrossRefGoogle Scholar
  8. 8.
    Natarajan TG, Ganesan N, Carter-Nolan P et al (2006) gamma-Radiation-induced chromosomal mutagen sensitivity is associated with breast cancer risk in African-American women: caffeine modulates the outcome of mutagen sensitivity assay. Cancer Epidemiol Biomarkers Prev 15(3):437–442PubMedCrossRefGoogle Scholar
  9. 9.
    Parshad R, Sanford KK (2001) Radiation-induced chromatid breaks and deficient DNA repair in cancer predisposition. Crit Rev Oncol Hematol 37(2):87–96PubMedCrossRefGoogle Scholar
  10. 10.
    Parshad R, Price FM, Bohr VA et al (1996) Deficient DNA repair capacity, a predisposing factor in breast cancer. Br J Cancer 74(1):1–5PubMedCrossRefGoogle Scholar
  11. 11.
    Patel RK, Trivedi AH, Arora DC, Bhatavdekar JM, Patel DD (1997) DNA repair proficiency in breast cancer patients and their first-degree relatives. Int J Cancer 73(1):20–24PubMedCrossRefGoogle Scholar
  12. 12.
    Scott D, Spreadborough AR, Jones LA, Roberts SA, Moore CJ (1996) Chromosomal radiosensitivity in G2-phase lymphocytes as an indicator of cancer predisposition. Radiat Res 145(1):3–16PubMedCrossRefGoogle Scholar
  13. 13.
    Zheng YL, Loffredo CA, Yu Z et al (2003) Bleomycin-induced chromosome breaks as a risk marker for lung cancer: a case–control study with population and hospital controls. Carcinogenesis 24(2):269–274PubMedCrossRefGoogle Scholar
  14. 14.
    Cloos J, Spitz MR, Schantz SP et al (1996) Genetic susceptibility to head and neck squamous cell carcinoma. J Natl Cancer Inst 88(8):530–535PubMedCrossRefGoogle Scholar
  15. 15.
    Spitz MR, Hoque A, Trizna Z et al (1994) Mutagen sensitivity as a risk factor for second malignant tumors following malignancies of the upper aerodigestive tract. J Natl Cancer Inst 86(22):1681–1684PubMedCrossRefGoogle Scholar
  16. 16.
    Wu X, Gu J, Patt Y et al (1998) Mutagen sensitivity as a susceptibility marker for human hepatocellular carcinoma. Cancer Epidemiol Biomarkers Prev 7(7):567–570PubMedGoogle Scholar
  17. 17.
    World Health Organization IAfRoC (2004) IARC monographs on the evaluation of carcinogenic risks to humans. IARC Press. Report No.: 83-Tobacco Smoke and Involuntary SmokingGoogle Scholar
  18. 18.
  19. 19.
    Collishaw N, Boyd N, Cantor K (2009) Canadian expert panel on tobacco smoke and breast cancer risk. OTRU Special Report Series 2009Google Scholar
  20. 20.
    Hsu TC, Johnston DA, Cherry LM et al (1989) Sensitivity to genotoxic effects of bleomycin in humans: possible relationship to environmental carcinogenesis. Int J Cancer 43(3):403–409PubMedCrossRefGoogle Scholar
  21. 21.
    Hoeijmakers JH (2001) Genome maintenance mechanisms for preventing cancer. Nature 411(6835):366–374PubMedCrossRefGoogle Scholar
  22. 22.
    Berwick M, Vineis P (2000) Markers of DNA repair and susceptibility to cancer in humans: an epidemiologic review. J Natl Cancer Inst 92(11):874–897PubMedCrossRefGoogle Scholar
  23. 23.
    Spitz MR, Wei Q, Dong Q, Amos CI, Wu X (2003) Genetic susceptibility to lung cancer: the role of DNA damage and repair. Cancer Epidemiol Biomarkers Prev 12(8):689–698PubMedGoogle Scholar
  24. 24.
    Burger RM, Peisach J, Horwitz SB (1981) Mechanism of bleomycin action: in vitro studies. Life Sci 28(7):715–727PubMedCrossRefGoogle Scholar
  25. 25.
    Dar ME, Winters TA, Jorgensen TJ (1997) Identification of defective illegitimate recombinational repair of oxidatively-induced DNA double-strand breaks in ataxia-telangiectasia cells. Mutat Res 384(3):169–179PubMedCrossRefGoogle Scholar
  26. 26.
    Xu YJ, Kim EY, Demple B (1998) Excision of C-4′-oxidized deoxyribose lesions from double-stranded DNA by human apurinic/apyrimidinic endonuclease (Ape1 protein) and DNA polymerase beta. J Biol Chem 273(44):28837–28844PubMedCrossRefGoogle Scholar
  27. 27.
    Jyothish B, Ankathil R, Chandini R et al (1998) DNA repair proficiency: a potential marker for identification of high risk members in breast cancer families. Cancer Lett 124(1):9–13PubMedCrossRefGoogle Scholar
  28. 28.
    Xiong P, Bondy ML, Li D et al (2001) Sensitivity to benzo(a)pyrene diol-epoxide associated with risk of breast cancer in young women and modulation by glutathione S-transferase polymorphisms: a case–control study. Cancer Res 61(23):8465–8469PubMedGoogle Scholar
  29. 29.
    Wang LE, Han CH, Xiong P, Bondy ML, Yu TK, Brewster AM, Shete S, Arun BK, Buchholz TA, Wei Q (2012) Gamma-ray-induced mutagen sensitivity and risk of sporadic breast cancer in young women: a case–control study. Breast cancer Res Treat 132(3):1147–1155Google Scholar
  30. 30.
    Reynolds P, Goldberg D, Hurley S, Nelson DO, Largent J, Henderson KD, Bernstein L (2009) Passive smoking and risk of breast cancer in the California teachers study. Cancer Epidemiol Biomarkers Prev 18(12):3389–3398Google Scholar
  31. 31.
    Pirie K, Beral V, Peto R et al (2008) Passive smoking and breast cancer in never smokers: prospective study and meta-analysis. Int J Epidemiol 37(5):1069–1079PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Mingbai Hu
    • 1
  • Dingfen Han
    • 2
  • Shengron Sun
    • 3
  • Yaqun Yan
    • 4
  • Jingwei Zhang
    • 1
  • Yunfeng Zhou
    • 1
  1. 1.Department of Oncology, Zhongnan Hospital of Wuhan UniversityHubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study CenterWuhanChina
  2. 2.Division of Geriatric Psychiatry, Department of Psychiatry and Behavioral Science, Johns Hopkins School of MedicineJohns Hopkins Bayview Medical CenterBaltimoreUSA
  3. 3.Department of Breast and Thyroid SurgeryRenmin Hospital of Wuhan UniversityWuhanChina
  4. 4.Wuhan Center for Disease Control and PreventionWuhanChina

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