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

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 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.

• Authors: M Krajinovic, P Ghadirian, C Richer, H Sinnett, S Gandini, C Perret, A Lacroix, D Labuda, D Sinnett
• Journal: International journal of cancer (Int J Cancer) Vol. 92 Issue 2 Pg. 220-5 (Apr 15 2001) ISSN: 0020-7136 [Print] United States
• PMID: 11291049 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2001 Wiley-Liss, Inc.

Chemical References

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

Topics

• Arylamine N-Acetyltransferase (genetics)
• Breast Neoplasms (enzymology, epidemiology, genetics)
• Canada (epidemiology)
• Carcinogens (metabolism)
• Carcinoma (enzymology, epidemiology, 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