Cytochrome P450 CYP1B1 and catechol O -methyltransferase ( COMT ) genetic polymorphisms and breast cancer susceptibility in a Turkish population

Abstract

Epidemiological studies indicate that most risk factors for breast cancer are related to reproductive and hormonal factors. Estrogen has been proposed to trigger breast cancer development via an initiating mechanism involving its metabolite, catechol estrogen (CE). Because of the important role of cytochrome P450 1B1 ( CYP1B1) and catechol O-methyltransferase ( COMT) in mammary estrogen and carcinogen metabolism, we examined the CYP1B1 and COMT genes to determine whether genetic variations could account for inter-individual differences in breast cancer. In this case-control study, we determined CYP1B1 and COMT genotypes in 84 breast cancer patients and 103 healthy unrelated women controls from a Turkish population. In the case of CYP1B1, we genotyped CYP1B1*3 (L432 V) allele. We found that carriers of the CYP1B1*3 allele were more frequent among breast cancer patients with adjusted odds ratio (OR) for age, age at menarche, age at first full-term pregnancy, body mass index (BMI) and smoking status of 2.32 (95% confidence interval 1.26-4.25) associated with the allele. However, this allele appeared to be a significant factor for susceptibility only in patients with a BMI greater than 24 kg/m(2). Menopausal status did not appear to affect susceptibility. In the case of COMT, there was no significant difference in susceptibility for breast cancer development between patients with low activity COMT-L (V158 M) allele and high activity COMT-H allele, and susceptibility was not affected by menopausal status, BMI or CYP1B1 genotype. We conclude that the CYP1B1* 3 allele appears to be a factor for susceptibility to breast cancer in Turkish women especially those with a BMI greater than 24 kg/m(2).

Cytochrome P450 1B1 and Catechol-O-Methyltransferase Genetic Polymorphisms and Breast Cancer Risk in Chinese Women: Results from the Shanghai Breast Cancer Study and a Meta-analysis

“…Yim et al (13) found that breast cancer risk was increased among carriers of the low-activity COMT allele compared with noncarriers (OR, 1.7; 95% CI, 1.04-2.78). Again however, this association was not replicated in other studies (8,(14)(15)(16)(17)(18). Herein, we report the results from a large population-based case-control study that has comprehensively evaluated the associations of CYP1B1 and COMT genetic polymorphisms with breast cancer risk, as well as the modifying effects of these polymorphisms on the association between estrogen exposure and breast cancer risk.…”

“…However, the findings from these studies have been inconsistent, and no convincing conclusions have been drawn due, at least in part, to the ethnic differences of the study populations, the inherent limitations of study designs, and small sample sizes. For instance, Kocabas et al (8) reported that carriers of CYP1B1 codon 432 Val allele (Val/Leu + Val/Val) in Turkish women had a higher risk of breast cancer than those with the Leu/Leu genotype [odds ratio (OR), 2.32; 95% confidence interval (CI), 1.26-4.25]. This association, however, was not observed in other studies (9)(10)(11)(12), including a large recent case-control study with 1,521 cases and 1,498 controls conducted in Swedish women (9).…”

Changes in 2-Hydroxyestrone and 16α-Hydroxyestrone Metabolism with Flaxseed Consumption: Modification by COMT and CYP1B1 Genotype

“…Genotyping for COMT was conducted using a method similar to that of Kocabas et al (14). Total genomic DNA was isolated from the buffy coat layer of blood according to the manufacturer's instructions for the QIAamp DNA Blood Mini kit (Qiagen, Valencia, CA).…”

Pharmacogenetics and Regulation of Human CytochromeP450 1B1: Implications in Hormone-Mediated Tumor Metabolism and a Novel Target for Therapeutic Intervention

“…However, the same study showed that no individual SNP examined had >60% predictive power when assessing cancer risk. Several case-control and family-based studies have shown that individuals with two hyperactive 432V alleles are at increased risk for developing breast cancer (14,43,129,130), whereas many have indicated that this allele is not associated with an individual's breast cancer risk (refs. 124, 131-135; see Table 3).…”