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

M. Krajinovic, P. Ghadirian, C. Richer, H. Sinnett, S. Gandini, C. Perret, A. Lacroix, D. Labuda, D. Sinnett

Research output: Contribution to journalArticle

Abstract

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 acetylatots 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.

Original languageEnglish
Pages (from-to)220-225
Number of pages6
JournalInternational Journal of Cancer
Volume92
Issue number2
DOIs
Publication statusPublished - Apr 15 2001

Keywords

  • Breast cancer
  • Cytochrome P-450
  • Genetic polymorphism
  • Genotype
  • Glutathione-S-transferase
  • N-acetyltransferase
  • Xenobiotic metabolism

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Genetic susceptibility to breast cancer in French-Canadians: Role of carcinogen-metabolizing enzymes and gene-environment interactions'. Together they form a unique fingerprint.

  • Cite this