ABSTRACT
Genetic polymorphisms of enzymes involved in the metabolism of xenobiotics and estrogens might play a role in breast carcinogenesis related to environmental exposures. In a case-only study on 282 women with breast cancer, we studied the interaction effects (ORi) between smoking habits and the gene polymorphisms of Cytochrome P450 1B1 (Val432Leu CYP1B1), Phenol-sulfotransferase 1A1 (Arg213His SULT1A1) and Catechol-O-methyltransferase (Val158Met COMT). The smokers carrying the Val CYP1B1 allele associated with a high hydroxylation activity had a higher risk of breast cancer than never smokers with the Leu/Leu genotype (ORi=2.32, 95%CI: 1.00-5.38). Also, the smokers carrying the His SULT1A1 allele associated with a low sulfation activity had a 2-fold excess risk compared to never smokers carrying Arg/Arg SULT1A1 common genotype (ORi= 2.55, 95%CI: 1.21-5.36). The His SULT1A1 allele increased the risk only in premenopausal patients. The Met COMT allele with a lower methylation activity than Val COMT did not modify the risk among smokers. The excess risk due to joint effect could result from a higher exposure to activated tobacco-compounds for women homo/heterozygous for the Val CYP1B1 allele. Also, a lower sulfation of the tobacco carcinogens among women with His SULT1A1 could increase exposure to genotoxic compounds. Alternatively, the Val CYP1B1 or His SULT1A1 allele with modified ability to metabolize estrogens could increase the level of genotoxic catechol estrogen (i.e., 4-hydroxy-estradiol) among smokers. Our study showed that gene polymorphisms of CYP1B1 and SULT1A1 induce an individual susceptibility to breast cancer among current smokers.
Subject(s)
Aryl Hydrocarbon Hydroxylases/genetics , Arylsulfotransferase , Breast Neoplasms/genetics , Catechol O-Methyltransferase/genetics , Polymorphism, Genetic , Smoking , Sulfotransferases/genetics , Adult , Aged , Aged, 80 and over , Alleles , Breast Neoplasms/epidemiology , Cytochrome P-450 CYP1B1 , DNA, Neoplasm/genetics , Drug Interactions , Female , Genetic Predisposition to Disease , Genotype , Humans , Middle Aged , Polymerase Chain Reaction , Risk FactorsABSTRACT
The role of plasma oxidant-antioxidant status in survival after breast cancer surgery was investigated in a cohort of patients (n = 363) hospitalized in Southern France between 1989 and 1992. The median follow-up was 8 years after surgery for histologically confirmed breast cancer. Plasma analyses were performed after diagnosis and before surgery and adjuvant therapy. We found an inverse relationship between plasma lipoperoxides (MDA) and tumor size at diagnosis, together with higher lipoperoxide levels in node-negative tumors than in node-positive ones (TNM). The longitudinal approach revealed an increased risk of recurrence for patients with plasma lipoperoxides in the highest tertile of the sample (RR = 2.1, 95% CI 1.1-4.0). In addition, the risk of recurrence increased (RR = 1.7, 95%CI 1.0-3.0), after adjustment for the known prognostic factors (TNM), for patients with plasma lipid-adjusted vitamin E levels of over 22 micromol/l. The risk of breast cancer death was twice as great for patients with plasma lipid-adjusted vitamin E levels above this value. Excesses of plasma lipoperoxides and vitamin E appear to be factors in poor prognosis for breast cancer-specific survival (OVS) and disease-free survival (DFS), respectively, independent of tumor characteristics at diagnosis. Several hypotheses are advanced to explain the possible role of plasma vitamin E as a factor in poor prognosis for survival.
