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Smoking and risk of breast cancer in carriers of mutations in BRCA1 or BRCA2 aged less than 50 years

  • Epidemiology
  • Published:
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Abstract

Background

Cigarette smoke contains compounds that may damage DNA, and the repair of damage may be impaired in women with germline mutations in BRCA1 or BRCA2. However, the effect of cigarette smoking on breast cancer risk in mutation carriers is the subject of conflicting reports. We have examined the relation between smoking and breast cancer risk in non-Hispanic white women under the age of 50 years who carry a deleterious mutation in BRCA1 or BRCA2.

Methods

We conducted a case-control study using data from carriers of mutations in BRCA1 (195 cases and 302 controls) and BRCA2 (128 cases and 179 controls). Personal information, including smoking history, was collected using a common structured questionnaire by eight recruitment sites in four countries. Odds-ratios (OR) for breast cancer risk according to smoking were adjusted for age, family history, parity, alcohol use, and recruitment site.

Results

Compared to non-smokers, the OR for risk of breast cancer for women with five or more pack-years of smoking was 2.3 (95% confidence interval 1.6–3.5) for BRCA1 carriers and 2.6 (1.8–3.9) for BRCA2 carriers. Risk increased 7% per pack-year (p < 0.001) in both groups.

Conclusions

These results indicate that smoking is associated with increased risk of breast cancer before age 50 years in BRCA1 and BRCA2 mutation carriers. If confirmed, they provide a practical way for carriers to reduce their risks. Previous studies in prevalent mutation carriers have not shown smoking to increase risk of breast cancer, but are subject to bias, because smoking decreases survival after breast cancer.

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References

  1. Perera FP, Estabrook A, Hewer A (1995) Carcinogen-DNA adducts in human breast tissue. Cancer Epidemiol Biomarkers Prev 4(3):233–238

    PubMed  CAS  Google Scholar 

  2. Baron JA, La Vecchia C, Levi F (1990) The antiestrogenic effect of cigarette smoking in women. Am J Obstet Gynecol 162(2):502–514

    PubMed  CAS  Google Scholar 

  3. Lesko SM, Rosenberg L, Kaufman DW, Helmrich SP, Miller DR, Strom BL (1985) Cigarette smoking and the risk of endometrial cancer. N Engl J Med 313(10):593–596

    Article  PubMed  CAS  Google Scholar 

  4. Williams AR, Weiss NS, Ure CI, Ballard J, Daling JR (1982) Effect of weight, smoking, and estrogen use on the risk of hip and forearm fractures in postmenopausal women. Obstet Gynecol 60(6):695–699

    PubMed  CAS  Google Scholar 

  5. MacMahon B, Trichopoulos D, Cole P (1982) Cigarette smoking and urinary estrogens. N Engl J Med 307(17):1062–1065

    Article  PubMed  CAS  Google Scholar 

  6. Terry PD, Rohan TE (2002) Cigarette smoking and the risk of breast cancer in women: a review of the literature. Cancer Epidemiol Biomarkers Prev 11(10 Pt 1):953–971

    PubMed  Google Scholar 

  7. Hamajima N, Hirose K, Tajima K et al (2002) Alcohol, tobacco and breast cancer—collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease. Br J Cancer 87(11):1234–1245

    Article  PubMed  CAS  Google Scholar 

  8. Johnson KC (2005) Accumulating evidence on passive and active smoking and breast cancer risk. Int J Cancer 117(4):619–628

    Article  PubMed  CAS  Google Scholar 

  9. Stern MC, Umbach DM, van Gils CH, Lunn RM, Taylor JA (2001) DNA repair gene XRCC1 polymorphisms, smoking, and bladder cancer risk. Cancer Epidemiol Biomarkers Prev 10(2):125–131

    PubMed  CAS  Google Scholar 

  10. Struewing JP, Hartge P, Wacholder S et al (1997) The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med 336(20):1401–1408

    Article  PubMed  CAS  Google Scholar 

  11. Thorlacius S, Struewing JP, Hartge P (1998) Population-based study of risk of breast cancer in carriers of BRCA2 mutation. Lancet 352(9137):1337–1339

    Article  PubMed  CAS  Google Scholar 

  12. Hopper JL, Southey MA, Dite GS et al (1999) Population-based estimate of the average age-specific cumulative risk of breast cancer for a defined set of protein-truncating mutations in BRCA1 and BRCA2. Australian Breast Cancer Family Study. Cancer Epidemiol Biomarkers Prev 8(9):741–747

    CAS  Google Scholar 

  13. Haile RW, Thomas DC, McGuire V et al (2006) BRCA1 and BRCA2 mutation carriers, oral contraceptive use and breast cancer before age 50. Cancer Epidemiol Biomarkers Prev 0(0):0

    Google Scholar 

  14. McGuire V, John EM, Felberg A et al (2006) No increased risk of breast cancer associated with alcohol consumption among carriers of BRCA1 and BRCA2 mutations ages < 50 years. Cancer Epidemiol Biomarkers Prev 15(8):1565–1567

    Article  PubMed  CAS  Google Scholar 

  15. John EM, Hopper JL, Beck JC et al (2004) An infrastructure for cooperative multinational, interdisciplinary and translational studies of the genetic epidemiology of breast cancer. Breast Cancer Res 6(4):R375–R389

    Article  PubMed  Google Scholar 

  16. Mann GJ, Thorne H, Balleine RL et al (2006) Analysis of cancer risk and BRCA1 and BRCA2 mutation prevalence in the kConFab familial breast cancer resource. Breast Cancer Res 8(1):R12

    Article  PubMed  CAS  Google Scholar 

  17. Andrulis IL, Anton-Culver H, Beck J et al (2002) Comparison of DNA- and RNA-based methods for detection of truncating BRCA1 mutations. Hum Mutat 20(1):65–73

    Article  PubMed  CAS  Google Scholar 

  18. Whittemore AS, Halpern J (2003) Logistic regression of family data from retrospective study designs. Genet Epidemiol 25(3):177–189

    Article  PubMed  Google Scholar 

  19. Antoniou A, Pharoah PD, Narod S et al (2003) Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 72(5):1117–1130

    Article  PubMed  CAS  Google Scholar 

  20. Brunet JS, Ghadirian P, Rebbeck T et al (1998) Effect of smoking on breast cancer in carriers of mutant BRCA1 and BRCA2 genes. J Natl Cancer Inst 90(1):761–765

    Article  PubMed  CAS  Google Scholar 

  21. Ghadirian P, Lubinski J, Lynch H et al (2004) Smoking and the risk of breast cancer among carriers of BRCA mutations. Int J Cancer 110(3):413–416

    Article  PubMed  CAS  Google Scholar 

  22. Gronwald J, Byrski T, Huzarski T et al (2006) Influence of selected lifestyle factors on breast and ovarian cancer risk in BRCA1 mutation carriers from Poland. Breast Cancer Res Treat 95(2):105–109

    Article  PubMed  Google Scholar 

  23. Colilla S, Kantoff PW, Neuhausen SL et al (2006) The joint effect of smoking and AIB1 on breast cancer risk in BRCA1 mutation carriers. Carcinogenesis 27(3):599–605

    Article  PubMed  CAS  Google Scholar 

  24. Nkondjock A, Robidoux A, Paredes Y, Narod SA, Ghadirian P (2006) Diet, lifestyle and BRCA-related breast cancer risk among French–Canadians. Breast Cancer Res Treat 98(3):285–294

    Article  PubMed  CAS  Google Scholar 

  25. Baron JA, Haile RW (1998) Protective effect of cigarette smoking on breast cancer risk in women with BRCA1 or BRCA2 mutations. J Natl Cancer Inst 90(10):726–727

    Article  PubMed  CAS  Google Scholar 

  26. Sackett D (1979) Bias in analytic research. J Chron Dis 32(1–2):51–63

    Article  PubMed  CAS  Google Scholar 

  27. Calle EE, Miracle-McMahill HL, Thun MJ, Heath CW Jr (1994) Cigarette smoking and risk of fatal breast cancer. Am J Epidemiol 139(10):1001–1007

    PubMed  CAS  Google Scholar 

  28. Yu GP, Ostroff JS, Zhang ZF, Tang J, Schantz SP (1997) Smoking history and cancer patient survival: a hospital cancer registry study. Cancer Detect Prev 21(6):497–509

    PubMed  CAS  Google Scholar 

  29. Manjer J, Andersson I, Berglund G et al (2000) Survival of women with breast cancer in relation to smoking. Eur J Surg 166(11):852–858

    Article  PubMed  CAS  Google Scholar 

  30. Scanlon EF, Suh O, Murthy SM, Mettlin C, Reid SE, Cummings KM (1995) Influence of smoking on the development of lung metastases from breast cancer. Cancer 75(11):2693–2699

    Article  PubMed  CAS  Google Scholar 

  31. Fentiman IS, Allen DS, Hamed H (2005) Smoking and prognosis in women with breast cancer. Int J Clin Pract 59(9):999–1000

    Article  Google Scholar 

  32. Al-Delaimy WK, Cho E, Chen WY, Colditz G, Willet WC (2004) A prospective study of smoking and risk of breast cancer in young adult women. Cancer Epidemiol Biomarkers Prev 13(3):398–404

    PubMed  Google Scholar 

  33. Reynolds P, Hurley S, Goldberg DE et al (2004) Active smoking, household passive smoking and breast cancer: evidence from the California teachers study. J Natl Cancer Inst 96(1):29–37

    Article  PubMed  CAS  Google Scholar 

  34. Gram IT, Braaten T, Terry PD et al (2005) Breast cancer risk among women who start smoking as teenagers. Cancer Epidemiol Biomarkers Prev 14(1):61–66

    PubMed  Google Scholar 

  35. Couch FJ, Cerhan JR, Vierkant RA et al (2001) Cigarette smoking increases risk for breast cancer in high-risk breast cancer families. Cancer Epidemiol Biomarkers Prev 10(4):327–332

    PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by the National Cancer Institute under RFA #CA-95-003, and through cooperative agreements with the University of Melbourne, Northern California Cancer Center, Cancer Care Ontario, the Fox Chase Cancer Center, Huntsman Cancer Institute, and Columbia University as part of the Breast Cancer Family Registry (Breast CFR), and by a grant from the National Institutes of Health (RO1 CA097359, PI: Dr A Whittemore). The Kathleen Cuningham Consortium for Research into Familial Breast Cancer is supported by the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) of Australia, and The Cancer Councils of Queensland, New South Wales, Western Australia, South Australia, and Victoria. Prof. Hopper is a NHMRC Principal Research Fellow and a Victorian Breast Cancer Research Consortium Group Leader. Dr Boyd is supported by the Lau Chair in Breast Cancer Research.

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Authors and Affiliations

    Consortia

    Breast Cancer Family Registry

    Kathleen Cuningham Consortium for Research into Familial Breast Cancer (Australasia)

    Ontario Cancer Genetics Network (Canada)

    Additional information

    Northern California Family Registry for Breast Cancer: AS Whittemore, Stanford University School of Medicine, EM John, Northern California Cancer Center, A Felberg, Stanford University School of Medicine, V McGuire, Stanford University School of Medicine, DW West, Northern California Cancer Center, A Miron, Dana-Farber Cancer Institute, Harvard Medical School, DC Thomas, USC Keck School of Medicine, R Haile, USC Keck School of Medicine and Norris Comprehensive Cancer. Fox Chase Familial Breast Cancer Registry: M Daly, Fox Chase Cancer Center, A Godwin, Fox Chase Cancer Center, E Ross, Fox Chase Cancer Center. Coriell Institute: J Beck. New York Familial Breast Cancer Registry: MB Terry, Joseph L. Mailman School of Public Health, Columbia University. Utah Breast Cancer Family Registry: SS Buys, Huntsman Cancer Institute, V Venne, Huntsman Cancer Institute. Australian Breast Cancer Family Study: JL Hopper, The University of Melbourne, GG Giles, The Cancer Council Victoria, MRE McCredie, University of Otago, New Zealand, RL Milne, Spanish National Cancer Centre, MC Southey, The University of Melbourne, MA Jenkins, The University of Melbourne, C Apicella, The University of Melbourne. Kathleen Cuningham Consortium for Research into Familial Breast Cancer (kConFab), Peter MacCallum Cancer Centre. Ontario Familial Breast Cancer Registry: I Andrulis, Cancer Care Ontario, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, NF Boyd, Ontario Cancer Institute, J Knight, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, H Ozcelik, Samuel Lunenfeld Research Institute, Mount Sinai Hospital. Correspondence to: Dr NF Boyd, Campbell Family Institute for Breast Cancer Research, Room 10-415, Ontario Cancer Institute, 610 University Ave., Toronto, Ontario, Canada M5G 2M9. Boyd@uhnres.utoronto.ca

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    Breast Cancer Family Registry., Kathleen Cuningham Consortium for Research into Familial Breast Cancer (Australasia). & Ontario Cancer Genetics Network (Canada). Smoking and risk of breast cancer in carriers of mutations in BRCA1 or BRCA2 aged less than 50 years. Breast Cancer Res Treat 109, 67–75 (2008). https://doi.org/10.1007/s10549-007-9621-9

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    • DOI: https://doi.org/10.1007/s10549-007-9621-9

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