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.
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References
Bray F, McCarron P, Parkin DM (2004) The changing global patterns of female breast cancer incidence and mortality. Breast Cancer Res 6(6):229–239
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):915–921
Turnbull C, Rahman N (2008) Genetic predisposition to breast cancer: past, present, and future. Annu Rev Genomics Hum Genet 9:321–345
Martin AM, Weber BL (2000) Genetic and hormonal risk factors in breast cancer. J Natl Cancer Inst 92(14):1126–1135
McPherson K, Steel CM, Dixon JM (2000) ABC of breast diseases. Breast cancer-epidemiology, risk factors, and genetics. BMJ 321(7261):624–628
Scully R (2000) Role of BRCA gene dysfunction in breast and ovarian cancer predisposition. Breast Cancer Res 2(5):324–330
Helzlsouer KJ, Harris EL, Parshad R et al (1996) DNA repair proficiency: potential susceptibility factor for breast cancer. J Natl Cancer Inst 88(11):754–755
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):437–442
Parshad R, Sanford KK (2001) Radiation-induced chromatid breaks and deficient DNA repair in cancer predisposition. Crit Rev Oncol Hematol 37(2):87–96
Parshad R, Price FM, Bohr VA et al (1996) Deficient DNA repair capacity, a predisposing factor in breast cancer. Br J Cancer 74(1):1–5
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):20–24
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):3–16
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):269–274
Cloos J, Spitz MR, Schantz SP et al (1996) Genetic susceptibility to head and neck squamous cell carcinoma. J Natl Cancer Inst 88(8):530–535
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):1681–1684
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):567–570
World Health Organization IAfRoC (2004) IARC monographs on the evaluation of carcinogenic risks to humans. IARC Press. Report No.: 83-Tobacco Smoke and Involuntary Smoking
CDC (2010) Smoking and tobacco use: GATS: Fact Sheet: China. http://www.cdc.gov/tobacco/global/gats/countries/wpr/fact_sheets/china/2010/index.htm. Available from: http://www.cdc.gov/tobacco/global/gats/countries/wpr/fact_sheets/china/2010/index.htm
Collishaw N, Boyd N, Cantor K (2009) Canadian expert panel on tobacco smoke and breast cancer risk. OTRU Special Report Series 2009
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):403–409
Hoeijmakers JH (2001) Genome maintenance mechanisms for preventing cancer. Nature 411(6835):366–374
Berwick M, Vineis P (2000) Markers of DNA repair and susceptibility to cancer in humans: an epidemiologic review. J Natl Cancer Inst 92(11):874–897
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):689–698
Burger RM, Peisach J, Horwitz SB (1981) Mechanism of bleomycin action: in vitro studies. Life Sci 28(7):715–727
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):169–179
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):28837–28844
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):9–13
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):8465–8469
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):1147–1155
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):3389–3398
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):1069–1079
Acknowledgments
We would like to thank Dr. Edith Gould, native speaker, for his critical reading and suggestions on the manuscript. This study was supported by the National Natural Science Foundation of China (No. 30672438). The Natural Science Foundation of Hubei Province (No. 301130851).
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The authors declare that they have no conflicts of interest.
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Hu, M., Han, D., Sun, S. et al. Bleomycin-induced mutagen sensitivity, passive smoking, and risk of breast cancer in Chinese women: a case–control study. Cancer Causes Control 24, 629–636 (2013). https://doi.org/10.1007/s10552-012-0137-1
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DOI: https://doi.org/10.1007/s10552-012-0137-1