Genetic susceptibility to breast cancer in French-Canadians: role of carcinogen-metabolizing enzymes and gene-environment interactions

Int J Cancer. 2001 Apr 15;92(2):220-5. doi: 10.1002/1097-0215(200102)9999:9999<::aid-ijc1184>;2-h.


Breast cancer is the most frequent malignancy among women. Since genetic factors such as BRCA1 and BRCA2 as well as reproductive history constitute only 30% of the cause, environmental exposure may play a significant role in the development of breast cancer. Likewise, the relevant enzymes involved in the biotransformation of xenobiotics (from tobacco smoke, diet or other environmental sources) might play a role in breast carcinogenesis. Since individuals with modified ability to metabolize these carcinogens could have a different risk for breast cancer, we investigated the role of cytochromes P-450 (CYP1A1, CYP2D6), glutathione-S-transferases (GSTM1, GSTT1, GSTP1) and N-acetyltransferases (NAT1, NAT2) gene variants in breast carcinogenesis. A case-control study was conducted on 149 women with breast carcinoma and 207 healthy controls, both of French-Canadian origin. The CYP1A1*4 allele was found to be a significant risk determinant of breast carcinoma (OR = 3.3, 95% CI 1.1-9.7), particularly among post-menopausal women (OR = 4.0, 95% CI 1.2-13.8). The frequency of NAT2 rapid acetylators was increased among smokers (OR = 2.6, 95% CI 0.8-8.2), while the NAT1*10 allele conferred a 4-fold increase in risk among women who consumed well-done meat (OR = 4.4, 95% CI 1.0-18.9). These data suggest that CYP1A1*4, NAT1 and NAT2 variants are involved in the susceptibility to breast carcinoma by modifying the impact of exogenous and/or endogenous exposures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arylamine N-Acetyltransferase / genetics
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Canada / epidemiology
  • Carcinogens / metabolism*
  • Carcinoma / enzymology*
  • Carcinoma / epidemiology
  • Carcinoma / genetics*
  • Case-Control Studies
  • Cytochrome P-450 CYP1A1 / genetics
  • Cytochrome P-450 CYP2D6 / genetics
  • Environmental Exposure
  • Female
  • France / ethnology
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genotype
  • Glutathione Transferase / genetics
  • Humans
  • Isoenzymes / genetics
  • Menopause
  • Middle Aged
  • Polymorphism, Genetic
  • Risk Factors


  • Carcinogens
  • Isoenzymes
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP2D6
  • Arylamine N-Acetyltransferase
  • N-acetyltransferase 1
  • NAT2 protein, human
  • Glutathione Transferase