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Genetic susceptibility to breast cancer in French‐Canadians: Role of carcinogen‐metabolizing enzymes and gene–environment interactions
Author(s) -
Krajinovic M.,
Ghadirian P.,
Richer C.,
Sinnett H.,
Gandini S.,
Perret C.,
Lacroix A.,
Labuda D.,
Sinnett D.
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(200102)9999:9999<::aid-ijc1184>3.0.co;2-h
Subject(s) - breast cancer , gstp1 , carcinogen , carcinogenesis , tobacco smoke , oncology , breast carcinoma , allele , risk factors for breast cancer , case control study , cancer , medicine , physiology , genetic predisposition , mammary gland , genetics , biology , gene , genotype , environmental health
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. © 2001 Wiley‐Liss, Inc.