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

110 Citations (Scopus)

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

Fingerprint

Gene-Environment Interaction
Genetic Predisposition to Disease
Carcinogens
Breast Neoplasms
Cytochrome P-450 CYP1A1
Enzymes
Carcinogenesis
Breast
Alleles
Cytochrome P-450 CYP2D6
Reproductive History
Acetyltransferases
Environmental Exposure
Xenobiotics
Biotransformation
Smoke
Meat
Tobacco
Case-Control Studies
Diet

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Genetic susceptibility to breast cancer in French-Canadians : Role of carcinogen-metabolizing enzymes and gene-environment interactions. / Krajinovic, M.; Ghadirian, P.; Richer, C.; Sinnett, H.; Gandini, S.; Perret, C.; Lacroix, A.; Labuda, D.; Sinnett, D.

In: International Journal of Cancer, Vol. 92, No. 2, 15.04.2001, p. 220-225.

Research output: Contribution to journalArticle

Krajinovic, M. ; Ghadirian, P. ; Richer, C. ; Sinnett, H. ; Gandini, S. ; Perret, C. ; Lacroix, A. ; Labuda, D. ; Sinnett, D. / Genetic susceptibility to breast cancer in French-Canadians : Role of carcinogen-metabolizing enzymes and gene-environment interactions. In: International Journal of Cancer. 2001 ; Vol. 92, No. 2. pp. 220-225.
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