Breast Cancer Research and Treatment

, Volume 114, Issue 1, pp 127–135 | Cite as

Smoking and the risk of breast cancer in BRCA1 and BRCA2 carriers: an update

  • Ophira Ginsburg
  • Parviz Ghadirian
  • Jan Lubinski
  • Cezary Cybulski
  • Henry Lynch
  • Susan Neuhausen
  • Charmaine Kim-Sing
  • Mark Robson
  • Susan Domchek
  • Claudine Isaacs
  • Jan Klijn
  • Susan Armel
  • William D. Foulkes
  • Nadine Tung
  • Pal Moller
  • Ping Sun
  • Steven A. Narod
  • Hereditary Breast Cancer Clinical Study Group


Among women with a mutation in BRCA1 or BRCA2, the risk of breast cancer is high, but it may be modified by exogenous and endogenous factors. There is concern that exposure to carcinogens in cigarette smoke may increase the risk of cancer in mutation carriers. We conducted a matched case–control study of 2,538 cases of breast cancer among women with a BRCA1 (n = 1,920) or a BRCA2 (n = 618) mutation. One non-affected mutation carrier control was selected for each case, matched on mutation, country of birth, and year of birth. Odds ratios were calculated using conditional logistic regression, adjusted for oral contraceptive use and parity. Ever-smoking was not associated with an increased breast cancer risk among BRCA1 carriers (OR = 1.09; 95% CI 0.95–1.24) or among BRCA2 carriers (OR = 0.81; 95% CI 0.63–1.05). The result did not differ when cases were restricted to women who completed the questionnaire within two years of diagnosis. A modest, but significant increase in risk was seen among BRCA1 carriers with a past history of smoking (OR = 1.27; 95% CI 1.06–1.50), but not among current smokers (OR = 0.95; 0.81–1.12). There appears to be no increase in the risk of breast cancer associated with current smoking in BRCA1 or BRCA2 carriers. There is a possibility of an increased risk of breast cancer among BRCA1 carriers associated with past smoking. There may be different effects of carcinogens in BRCA mutation carriers, depending upon the timing of exposure.


BRCA1 BRCA2 Smoking 



Breast cancer susceptibility gene 1


Breast cancer susceptibility gene 2


Odds ratio


Confidence interval


Deoxyribonucleic acid


Relative risk


Hazard ratio


  1. 1.
    Easton DF, Ford D, Bishop DT (1995) Breast and ovarian cancer incidence in BRCA1- mutation carriers. Breast Cancer Linkage Consortium. Am J Hum Genet 56:256–271Google Scholar
  2. 2.
    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 72:1117–1130PubMedCrossRefGoogle Scholar
  3. 3.
    Chen S, Iversen ES, Friebel T et al (2006) Characterization of BRCA1 and BRCA2 mutations in a large United States sample. J Clin Oncol 24:863–871PubMedCrossRefGoogle Scholar
  4. 4.
    Ghadirian P, Lubinski J, Lynch H et al (2004) Smoking and the risk of breast cancer among carriers of BRCA mutations. Int J Cancer 110:413–416PubMedCrossRefGoogle Scholar
  5. 5.
    Brunet JS, Ghadirian P, Rebbeck TR et al (1998) Effect of smoking on breast cancer in carriers of mutant BRCAI or BRCA2 genes. JNCI 90:761–766PubMedCrossRefGoogle Scholar
  6. 6.
    Breast Cancer Family Registry; Kathleen Cuningham Consortium for Research into Familial Breast Cancer (Australasia); Ontario Cancer Genetics Network (Canada) (2007) Smoking and risk of breast cancer in carriers of mutations in BRCA1 or BRCA2 aged less than 50 years. Breast Cancer Res Treat (Epub ahead of print)Google Scholar
  7. 7.
    Gronwald J, Byrski T, Huzarski T et al (2006) Influence of selected lifestyle factors on breast and ovarian cancer in BRCA1 mutation carriers from Poland. Breast Cancer Res Treat 95:105–109PubMedCrossRefGoogle Scholar
  8. 8.
    Nkondjock A, Robidoux A, Paredes Y et al (2006) Diet, lifestyle and BRCA-related breast cancer risk among French-Canadians. Breast Cancer Res Treat 98:285–294PubMedCrossRefGoogle Scholar
  9. 9.
    Collia S, Kantoff PW, Neuhausen SL et al (2006) The joint effect of smoking and AIB1 on breast cancer risk in BRCA1 mutation carriers. Carcinogenesis 27:599–605CrossRefGoogle Scholar
  10. 10.
    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 10:327–332PubMedGoogle Scholar
  11. 11.
    Reynolds P, Hurley S, Goldberg D et al (2004) Active smoking, passive smoking, and breast cancer: evidence from the California Teachers Study. J Natl Cancer Inst 96:29–37PubMedCrossRefGoogle Scholar
  12. 12.
    Bennicke K, Conrad C, Sabrae S et al (1995) Cigarette smoking and breast cancer. Br Med J 310:1431–1432Google Scholar
  13. 13.
    Braga C, Negri E, La Vecchia C et al (1996) Cigarette smoking and risk of breast cancer. Eur J Cancer Prev 5:159–164PubMedCrossRefGoogle Scholar
  14. 14.
    Lash TL, Aschengrau A (1999) Active and passive cigarette smoking and the occurrence of breast cancer. Am J Epidemiol 149:5–12PubMedGoogle Scholar
  15. 15.
    Marcus PM, Newman B, Millikan RC et al (2000) The associations of adolescent cigarette smoking, alcohol beverage consumption, environmental tobacco smoke, and ionizing radiation with subsequent breast cancer risk (United States). Cancer Causes Control 11:271–278PubMedCrossRefGoogle Scholar
  16. 16.
    Johnson KC, Hu J, Mao Y (2000) Passive and active smoking and breast cancer risk in Canada, 1994–97. The Canadian Cancer Registries Epidemiology Research Group. Cancer Causes Control 11:211–221PubMedCrossRefGoogle Scholar
  17. 17.
    Band PR, Le ND, Fang R et al (2002) Carcinogenic and endocrine disrupting effects of cigarette smoke and risk of breast cancer. Lancet 360:1044–1049PubMedCrossRefGoogle Scholar
  18. 18.
    Kropp S, Chang-Claude J (2002) Active and passive smoking and risk of breast cancer by age 50 years among German women. Am J Epidemiol 156:616–626PubMedCrossRefGoogle Scholar
  19. 19.
    Egan KM, Stampfer MJ, Hunter D et al (2002) active and passive smoking in breast cancer: prospective results from the Nurses’ Health Study. Epidemiology 13:138–145PubMedCrossRefGoogle Scholar
  20. 20.
    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):1234–1245PubMedCrossRefGoogle Scholar
  21. 21.
    Lawlor DA, Ebrahim S, Smith GD (2004) Smoking before the birth of a first child is not associated with increased risk of breast cancer: findings from the British Women Heart and Health Cohort Study and a meta-analysis. Br J Cancer 91:512–518PubMedCrossRefGoogle Scholar
  22. 22.
    Johnson JC (2005) Accumulating evidence on passive and active smoking and breast cancer risk. Int J Cancer 117:619–628PubMedCrossRefGoogle Scholar
  23. 23.
    Terry PD, Rohan TE (2002) Cigarette smoking and the risk of breast cancer in women: a review of the literature. Cancer Epidemiol Biomarkers Prev 11:953–971PubMedGoogle Scholar
  24. 24.
    Al-Delaimy WK, Cho E, Chen W et al (2004) A prospective study of smoking and risk of breast cancer in young adult women. Cancer Epidemiol Biomarkers Prev 13:398–404PubMedGoogle Scholar
  25. 25.
    Gram IT, Braaten T, Terry PD et al (2005) Breast cancer risk among women who start smoking as teenagers. Cancer Epidemiol Biomarkers Prev 14:61–66PubMedGoogle Scholar
  26. 26.
    London SJ, Colditz GA, Stampfer MJ et al (1989) Prospective study of smoking and the risk of breast cancer. J Natl Cancer Inst 81:1625–1631PubMedCrossRefGoogle Scholar
  27. 27.
    Morabia A, Bernstein M, Ruiz J et al (1998) Relation of smoking to breast cancer by estrogen receptor status. Int J Cancer 75:339–342PubMedCrossRefGoogle Scholar
  28. 28.
    Obana H, Hori S, Kashimoto T, Kunita N (1981) Polycyclic aromatic hydrocarbons in human fat and liver. Bull Environ Contam Toxicol 27:23–27PubMedCrossRefGoogle Scholar
  29. 29.
    IARC (1986) Tobacco smoking. IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans. IARC Sci Publ 38, IARC Lyon, France, pp 1–397Google Scholar
  30. 30.
    el-Bayoumy K (1992) Environmental carcinogens that may be involved in human breast cancer etiology. Chem Res Toxicol 5:585–590PubMedCrossRefGoogle Scholar
  31. 31.
    Morris JJ, Seifter E (1992) The role of aromatic hydrocarbons in the genesis of breast cancer. Med Hypotheses 38:177–184PubMedCrossRefGoogle Scholar
  32. 32.
    Hoffman D, Hoffman I, el-Bayoumy K (2001) The less harmful cigarette: a controversial issue. A tribute to Ernst L Wynder. Chem Res Toxicol 14:767–790CrossRefGoogle Scholar
  33. 33.
    Phillips DH, Martin FL, Grover PL, Williams JA (2001) Toxicological basis for a possible association of breast cancer with smoking and other sources of environmental carcinogens. J Women’s Cancer 2:9–16Google Scholar
  34. 34.
    Perera FP, Estabrook A, Hewer A (1995) Carcinogen-DNA adducts in human breast tissue. Cancer Epidemiol Biomarkers Prev 4:233–238PubMedGoogle Scholar
  35. 35.
    Kaufman DW, Slone D, Rosenberg L, Miettinen OS, Shapiro S (1980) Cigarette smoking, age at natural menopause. Am J Public Health 70:420–422PubMedCrossRefGoogle Scholar
  36. 36.
    Williams AR, Weiss NS, Ure CI et al (1982) Effect of weight, smoking, and estrogen use on the risk of hip and forearm fractures in postmenopausal women. Obstet Gynecol 60:695–699PubMedGoogle Scholar
  37. 37.
    MacMahon B, Trichopoulos D, Cole P et al (1982) Cigarette smoking and urinary estrogens. N Engl J Med 307:1062–1065PubMedGoogle Scholar
  38. 38.
    Baron JA, La Vecchia C, Levi F (1990) The antiestrogenic effect of cigarette smoking in women. Am J Obstet Gyneco1 162:502–514Google Scholar
  39. 39.
    Lesko SM, Rosenberg L, Kaufman DW et al (1985) Cigarette smoking and the risk of endometrial cancer. N Engl J Med 313:593–596PubMedGoogle Scholar
  40. 40.
    Hosey AM, Gorski JJ, Murray MM et al (2007) Molecular basis for estrogen receptor α deficiency in BRCA1-linked breast cancer. J Natl Cancer Inst 99:1683–1694PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Ophira Ginsburg
    • 1
  • Parviz Ghadirian
    • 2
  • Jan Lubinski
    • 3
  • Cezary Cybulski
    • 3
  • Henry Lynch
    • 4
  • Susan Neuhausen
    • 5
  • Charmaine Kim-Sing
    • 6
  • Mark Robson
    • 7
  • Susan Domchek
    • 8
  • Claudine Isaacs
    • 9
  • Jan Klijn
    • 10
  • Susan Armel
    • 11
  • William D. Foulkes
    • 12
  • Nadine Tung
    • 13
  • Pal Moller
    • 14
  • Ping Sun
    • 15
  • Steven A. Narod
    • 15
  • Hereditary Breast Cancer Clinical Study Group
    • 16
  1. 1.The Campbell Family Institute for Breast Cancer Research at Princess Margaret HospitalTorontoCanada
  2. 2.Epidemiology Research Unit, Centre Hospitalier de l’Universite de Montreal (CHUM) Hotel-Dieu, Faculty of MedicineUniversite de MontrealMontrealCanada
  3. 3.Pomeranian Medical UniversitySzczecinPoland
  4. 4.Department of Preventive Medicine and Public HealthCreighton University School of MedicineOmahaUSA
  5. 5.Department of EpidemiologyUniversity of CaliforniaIrvineUSA
  6. 6.British Columbia Cancer AgencyVancouverCanada
  7. 7.Clinical Genetics, Department of MedicineMemorial-Sloan KetteringNew YorkUSA
  8. 8.Departments of Medicine and GeneticsUniversity of PennsylvaniaPhiladelphiaUSA
  9. 9.Lombardi Cancer CenterGeorgetown University Medical CenterWashingtonUSA
  10. 10.Department of Medical Oncology, (Dr. Daniel den Hoed Kliniek) Rotterdam Cancer InstituteUniversity Hospital RotterdamRotterdamThe Netherlands
  11. 11.Department of Obstetrics and GynecologyUniversity Health NetworkTorontoCanada
  12. 12.Program in Cancer Genetics, Departments of Oncology and Human GeneticsMcGill UniversityMontrealCanada
  13. 13.Beth Israel Deaconess HospitalBostonUSA
  14. 14.Department for Cancer GeneticsThe Norwegian Radium HospitalOsloNorway
  15. 15.Womens College Research Institute, Women’s College HospitalUniversity of TorontoTorontoCanada
  16. 16.Womens College Research InstituteTorontoCanada

Personalised recommendations