Interaction between genetic polymorphism of cytochrome P450-1B1 and environmental pollutants in breast cancer risk.
Cytochrome P450 1B1 (CYP1B1) is implicated in the activation of potentially carcinogenic xenobiotics and oestrogens. The polymorphism of the CYP1B1 gene at codon 432 (Val-->Leu) is associated with change in catalytic function. In a case-series study of breast cancer patients, we investigated the interaction between this polymorphism and environmental exposure. The women carrying the Val CYP1B1 allele and who had lived near to a waste incinerator for more than 10 years had a higher risk of breast cancer than those never exposed with the Leu/Leu genotype (odds ratio of interactions (ORi)=3.26, 95% confidence interval (CI) 1.20-8.84). Also, the Val CYP1B1 allele increased the susceptibility to breast cancer for women exposed during their life to agricultural products used in farming (ORi = 2.18, 95% CI 1.10-4.32). These xenobiotics, mainly organochlorine hydrocarbons, are known to bind to the aromatic hydrocarbon receptor (AhR), and to induce the expression of CYP1B1 enzyme. The excess risk for exposed women with a Val CYP1B1 homo/heterozygous genotype could result from a higher exposure to activated metabolites of pesticides or dioxin-like substances. Also, a higher induction of CYP1B1 enzyme by xenobiotics could increase the formation of genotoxic catechol-oestrogens among exposed women carrying the Val CYP1B1 allele. Our results suggested that the Val CYP1B1 allele increases the susceptibility to breast cancer in women exposed to waste incinerator or agricultural pollutants.
Saintot
M
M
Groupe d'Epidémiologie Métabolique, Centre de Recherche en Cancérologie, INSERM-CRLC, 34298 Montpellier Cedex 5, France. marietger@valdorel.fnclcc.fr
Malaveille
C
C
Hautefeuille
A
A
Gerber
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000453:epidemiology / Q000209:etiology*; D002273:Carcinogens / Q000633:toxicity; D015331:Cohort Studies; D065633:Cytochrome P-450 CYP1B1; D004273:DNA, Neoplasm / Q000235:genetics; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000378:metabolism; D017745:Incineration; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D012307:Risk Factors
D002273:Carcinogens; D004273:DNA, Neoplasm; D004785:Environmental Pollutants; D006843:Hydrocarbons, Chlorinated; D018336:Receptors, Aryl Hydrocarbon; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1